Poretti, Andrea; Vitiello, Giuseppina; Hennekam, Raoul C. M.; Arrigoni, Filippo; Bertini, Enrico; Borgatti, Renato; Brancati, Francesco; D'Arrigo, Stefano; Faravelli, Francesca; Giordano, Lucio; Huisman, Thierry A. G. M.; Iannicelli, Miriam; Kluger, Gerhard; Kyllerman, Marten; Landgren, Magnus; Lees, Melissa M.; Pinelli, Lorenzo; Romaniello, Romina; Scheer, Ianina; Schwarz, Christoph E.; Spiegel, Ronen; Tibussek, Daniel; Valente, Enza Maria; Boltshauser, Eugen
Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome.
Peter W Duda
Full Text Available Oral-facial-digital syndrome (OFD is a collective term describing thirteen distinctive, rare genetic disorders based on inheritance pattern and phenotypic expression. OFD is characterized by malformations of the oral cavity, the maxillofacial region and the arms and legs. Central nervous system anomalies, include intracerebral cysts, agenesis of the corpus callosum, hydrocephalus, cerebral/cerebellar atrophy, and berry aneurysms. Some degree of compromised intellectual ability and speech are present in affected individuals that correlate with the degree of central nervous system involvement. Furthermore, renal involvement in the form of polycystic kidney disease is evident in affected individuals in adulthood. In this article, we present a 37-year-old female patient that presented to the Rutgers School of Dental Medicine with oral-facial-digital syndrome, type 1.
Chung Wongyiu; Chung Laupo
We report a child with clinical and radiological manifestations characteristic of both V'aradi syndrome (oral-facial-digital syndrome type VI) and Thurston syndrome (oral-facial-digital syndrome type V). The findings have not been reported previously, and we believe that it represents a new variant. (orig.)
Bouman, Arjan; Alders, Mariëlle; Oostra, Roelof Jan; van Leeuwen, Elisabeth; Thuijs, Nikki; van der Kevie-Kersemaekers, Anne-Marie; van Maarle, Merel
Oral-facial-digital syndrome type 1 (OFD1; OMIM# 311200) is an X-linked dominant ciliopathy caused by mutations in the OFD1 gene. This condition is characterized by facial anomalies and abnormalities of oral tissues, digits, brain, and kidneys. Almost all affected patients are female, as OFD1 is
Full Text Available Background. Oral-facial-digital syndrome type 1 (OFD1 is a rare condition with X-linked dominant inheritance caused by mutations in the Cxorf5 (OFD1 gene. This gene encodes the OFD1 protein located within centrosomes and basal bodies of primary cilia. Approximately 15–50% of patients with OFD1 progress to end-stage kidney disease following development of polycystic changes within the kidneys. This condition almost always causes intrauterine lethality in males. Description of Case Diagnosis and Treatment. A Caucasian male aged 9 years and 9 months presented with increased urinary frequency, increased thirst, and decreased appetite. Physical examination demonstrated short stature, hearing loss, photophobia, murmur, and hypogonadism. He had no other dysmorphic features. Laboratory results revealed anemia, renal insufficiency, and dilute urine with microscopic hematuria but no proteinuria. Ultrasound showed small kidneys with increased echogenicity but no evidence of cystic changes. A Ciliopathy Panel showed a novel and likely pathogenic deletion, approximately 7.9 kb, in the OFD1 gene encompassing exons 16, 17, and 19 (c.1654+833_2599+423del. Brain MRI did not demonstrate typical OFD1 findings. He is currently on chronic hemodialysis awaiting transplant from a living donor. Conclusions. We present a male patient with OFD1 mutation who lacks the classic OFD1 phenotype who presented with end-stage renal disease without evidence of polycystic changes within the kidneys.
Full Text Available Abstract Oral-Facial-Digital Syndrome type VI (OFD VI represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD. In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1 MTS and one oral finding and polydactyly, or 2 MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD
Bouman, Arjan; Alders, Mari?lle; Oostra, Roelof Jan; van Leeuwen, Elisabeth; Thuijs, Nikki; van der Kevie?Kersemaekers, Anne?Marie; van Maarle, Merel
Oral?facial?digital syndrome type 1 (OFD1; OMIM# 311200) is an X?linked dominant ciliopathy caused by mutations in the OFD1 gene. This condition is characterized by facial anomalies and abnormalities of oral tissues, digits, brain, and kidneys. Almost all affected patients are female, as OFD1 is presumed to be lethal in males, mostly in the first or second trimester of pregnancy. Live born males with OFD1 are a rare occurrence, with only five reported patients to date. In four patients the pr...
Franco, Brunella; Thauvin-Robinet, Christel
Oral-facial-digital syndromes (OFDS) represent a heterogeneous group of rare developmental disorders affecting the mouth, the face and the digits. Additional signs may involve brain, kidneys and other organs thus better defining the different clinical subtypes. With the exception of OFD types I and VIII, which are X-linked, the majority of OFDS is transmitted as an autosomal recessive syndrome. A number of genes have already found to be mutated in OFDS and most of the encoded proteins are predicted or proven to be involved in primary cilia/basal body function. Preliminary data indicate a physical interaction among some of those proteins and future studies will clarify whether all OFDS proteins are part of a network functionally connected to cilia. Mutations in some of the genes can also lead to other types of ciliopathies with partially overlapping phenotypes, such as Joubert syndrome (JS) and Meckel syndrome (MKS), supporting the concept that cilia-related diseases might be a continuous spectrum of the same phenotype with different degrees of severity. To date, seven of the described OFDS still await a molecular definition and two unclassified forms need further clinical and molecular validation. Next-generation sequencing (NGS) approaches are expected to shed light on how many OFDS geneticists should consider while evaluating oral-facial-digital cases. Functional studies will establish whether the non-ciliary functions of the transcripts mutated in OFDS might contribute to any of the phenotypic abnormalities observed in OFDS.
Young, L.W.; Wilhelm, L.L. [Loma Linda Univ., CA (United States). Medical Center; Zuppan, C.W. [Div. of Pediatric Pathology, Loma Linda University Medical Center, CA (United States); Clark, R. [Div. of Medical Genetics, Loma Linda University Medical Center, CA (United States)
A stillborn baby boy had findings of severe constitutional dwarfism with short limbs, short ribs, and polydactyly that were consistent with Naumoff (type III) short-rib polydactyly syndrome. He also had additional congenital anomalies, including cleft palate, notching of the upper lip, small tongue with accessory sublingual tissue. These oral and pharyngeal anomalies were consistent with Mohr (type II) oral-facial-digital syndrome. We suggest the stillborn infant represented a compound of Naumoff short-rib polydactyly syndrome (SRPS-III) and Mohr oral-facial-digital syndrome (OFDS-II). (orig.)
Rabah M. Shawky
Feb 28, 2014 ... Introduction. The Oral-facial-digital syndrome (OFDS) is a heterogeneous .... et al.  reported a common AV canal with pulmonary hyper- ....  Poretti A, Vitiello G, Hennekam RC, Arrigoni F, Bertini E, ... 2010;42(7):619–25.
Hayes, Laura L.; Palasis, Susan; Simoneaux, Stephen F.; Niyazov, Dmitriy M.
The oral-facial-digital syndromes (OFDS) comprise a group of disorders involving malformations of the mouth, face, and digits. There are 13 subtypes of the OFDS, and much overlap exists among OFDS patients. Distinct syndromes such as Joubert and Pallister-Hall display many of the same features. This report describes an infant with abnormalities including a hypoplastic/absent cerebellar vermis and forked third metacarpals, consistent with a diagnosis of OFDS type VI (Varadi-Papp). The girl's abnormalities also included malformations of the larynx and trachea, findings never before described in type VI but described in other OFDS subtypes and similar syndromes. Our patient represents a transitional OFDS type, further supporting evidence of a common molecular pathway among these disorders. This report highlights the importance of the radiologist's role in diagnosis. (orig.)
Lindeboom, Jerome A. H.; Kroon, Frans H. M.; de Vires, Jan; van den Akker, Hans P.
In 1954, Papillon-Leage and Psaume were the first to describe the clinical characteristics of oral-facial-digital syndrome (OFDS). On the basis of their clinical features and the inheritance pattern, 2 variants were initially distinguished, namely OFDS type I (Papillon-Leage and Psaume) and OFDS
Rabah M. Shawky
Full Text Available We report a 4 month old male infant, the first in order of birth of healthy first cousin consanguineous parents who has many typical features of oral-facial-digital syndrome type VI (OFDS VI including hypertelorism, bilateral convergent squint, depressed nasal bridge, and wide upturned nares, low set posteriorly rotated ears, long philtrum, gum hyperplasia with notches of the alveolar borders, high arched palate, and hyperplastic oral frenula. He has mesoaxial and postaxial, polysyndactyly which is the specific feature of OFDS VI, however the cerebellum is normal on MRI brain. He has also some rare congenital anomalies including common atrioventricular canal, hirschsprung disease, and sacral dysgenesis. This patient may have a transitional type between II and VI, a variant of type VI or a new type.
Bruel, Ange-Line; Franco, Brunella; Duffourd, Yannis; Thevenon, Julien; Jego, Laurence; Lopez, Estelle; Deleuze, Jean-François; Doummar, Diane; Giles, Rachel H.; Johnson, Colin A.; Huynen, Martijn A.; Chevrier, Véronique; Burglen, Lydie; Morleo, Manuela; Desguerres, Isabelle; Pierquin, Geneviève; Doray, Bérénice; Gilbert-Dussardier, Brigitte; Reversade, Bruno; Steichen-Gersdorf, Elisabeth; Baumann, Clarisse; Panigrahi, Inusha; Fargeot-Espaliat, Anne; Dieux, Anne; David, Albert; Goldenberg, Alice; Bongers, Ernie; Gaillard, Dominique; Argente, Jesús; Aral, Bernard; Gigot, Nadège; St-Onge, Judith; Birnbaum, Daniel; Phadke, Shubha R.; Cormier-Daire, Valérie; Eguether, Thibaut; Pazour, Gregory J.; Herranz-Pérez, Vicente; Lee, Jaclyn S.; Pasquier, Laurent; Loget, Philippe; Saunier, Sophie; Mégarbané, André; Rosnet, Olivier; Leroux, Michel R.; Wallingford, John B.; Blacque, Oliver E.; Nachury, Maxence V.; Attie-Bitach, Tania; Rivière, Jean-Baptiste; Faivre, Laurence; Thauvin-Robinet, Christel
Oral-facial-digital syndromes (OFDS) gather rare genetic disorders characterized by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFD subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 OFDS cases. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753, IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231, WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterizing three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the MKS module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these 3 main subtypes, a further classification could be based on the genotype. PMID:28289185
Chevrier, V.; Bruel, A.L.; Dam, T.J. van; Franco, B.; Scalzo, M. Lo; Lembo, F.; Audebert, S.; Baudelet, E.; Isnardon, D.; Bole, A.; Borg, J.P.; Kuentz, P.; Thevenon, J.; Burglen, L.; Faivre, L.; Riviere, J.B.; Huynen, M.A.; Birnbaum, D.; Rosnet, O.; Thauvin-Robinet, C.
Oral-facial-digital (OFD) syndromes are rare heterogeneous disorders characterized by the association of abnormalities of the face, the oral cavity and the extremities, some due to mutations in proteins of the transition zone of the primary cilia or the closely associated distal end of centrioles.
Rabah M. Shawky
Apr 16, 2013 ... VI, however mentality and MRI brain were nor- mal. This unusual association may suggest an ... urinary crystals between the 5th and 6th months of pregnancy, one injection for allergy at the 4th and again at the 8th month of pregnancy as well as vitamin supplementation. * Corresponding author. Address: ...
... related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits ( ... this disorder involve problems with development of the oral cavity , facial features, and digits. Most forms are also ...
Full Text Available Meckel syndrome (MKS is a lethal, autosomal recessive disorder characterized by occipital encephalocele, bilateral renal cystic dysplasia, hepatic ductal proliferation, fibrosis and cysts, and polydactyly. Genetic heterogeneity of MKS has been established by three reported MKS loci, i.e., MKS1 on 17q23, MKS2 on 11q13, and MKS3 on 8q21.13-q22.1. MKS1 encodes a component of flagellar apparatus basal body proteome, which is associated with ciliary function. MKS3 encodes a seven-transmembrane receptor protein, meckelin. The identification of the MKS3 gene as well as the MKS1 gene enables molecular genetic testing for at-risk families, and allows accurate genetic counseling, carrier testing, and prenatal diagnosis. Pregnancies with MKS fetuses may be associated with an elevated maternal serum α-fetoprotein level and an abnormal screening result in the second-trimester maternal serum screening test. The classic MKS triad of occipital encephalocele, postaxial polydactyly, and bilateral enlarged multicystic kidneys can be diagnosed before the 14th gestational weeks by ultrasonography. However, later in pregnancy, severe oligohydramnios may make the diagnosis of polydactyly and encephalocele difficult. Differential diagnosis for MKS includes autosomal recessive polycystic kidney disease, trisomy 13, Smith-Lemli-Opitz syndrome, hydrolethalus syndrome, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, and oral-facial-digital syndrome type 1. This article provides an overview of genetics, perinatal findings, and differential diagnosis of MKS. The ciliopathy underlies the pathogenesis of MKS. Prenatal diagnosis of bilateral enlarged multicystic kidneys should alert MKS and prompt a thorough investigation of central nervous system malformations and polydactyly.
EHLERS-DANLOS SYNDROME HYPERMOBILITY TYPE Ehlers-Danlos syndrome hypermobility type is a connective tissue disorder that mostly affects the bones and joints. People with this condition have loose joints ...
Khurana, Bhawna Piplani; Khurana, Aruj Kumar; Grover, Sumit
Duane retraction syndrome is characterized by globe retraction and palpebral fissure narrowing on adduction, with restriction of abduction, adduction, or both. Usher syndrome type 2 consists of congenital bilateral sensorineural hearing loss and retinitis pigmentosa. The authors present a case with a yet unreported association between Duane retraction syndrome type 1 and Usher syndrome type 2. Copyright 2015, SLACK Incorporated.
Praharaj, Samir Kumar; Acharya, Mahima; Sarvanan, Arul; Kongasseri, Sreejayan; Behere, Rishikesh V; Sharma, P S V N
Usher syndrome (or Hallgren syndrome) is an autosomal recessive genetic disorder characterized by sensorineural deafness, retinitis pigmentosa, and variable vestibular deficit; Usher syndrome type II is the most common form. Various neuropsychiatric disorders have been reported to occur in those with Usher syndrome, including schizophrenia-like disorder, atypical psychosis, recurrent depressive illness, neurotic disorder, and mental retardation; however, bipolar disorder is not common in those with Usher syndrome. Herein we describe a 30-year-old male with Usher syndrome type II that developed features indicative of a probable manic episode. The patient had complete remission of symptoms in response to treatment with olanzapine 20 mg d-1. In persons with dual sensory impairment there are inherent problems with assessment and diagnosis is difficult due to their limited communication abilities. The diagnosis of Usher syndrome depends heavily on behavioral observation and disturbances in vegetative functions.
... Conditions Type A insulin resistance syndrome Type A insulin resistance syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Type A insulin resistance syndrome is a rare disorder characterized by severe ...
... blepharophimosis-mental retardation syndrome, Maat-Kievit-Brunner type BMRS, MKB type Ohdo syndrome, MKB type X-linked ... D, Brunner H, Bitoun P. Blepharophimosis-mental retardation (BMR) syndromes: A proposed clinical classification of the so- ...
Pieke Dahl, S; Kimberling, WJ; Gorin, MB; Weston, MD; Furman, JM; Pikus, A; Moller, C
Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis ...
Maria Kiyoko Oyamada
Full Text Available OBJECTIVE: To report on a case of Pfeiffer Syndrome, with a discussion of the diagnostic characteristics and features of disease types and the differential diagnosis. DESCRIPTION: The authors describe a newborn with cloverleaf skull, extreme bilateral exorbitism and choanal atresia, partial syndactyly of the second and third toes and broad medially-deviated big toes. The case reported was Pfeiffer Syndrome type 2, which usually has a poor prognosis. COMMENTS: Pfeiffer Syndrome is a clinically variable disorder and consists of an autosomal dominantly-inherited osteochondrodysplasia with craniosynostosis. It has been divided into three types. Type 1 is commonly associated with normal intelligence and generally good outcome. Types 2 and 3 generally have severe neurological compromise, poor prognosis, early death and sporadic occurrence. Potential for prolonged useful survival outcome can be achieved in some cases with early aggressive medical and surgical management according to recent literature.
Germain Dominique P
Full Text Available Abstract Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS, is an inherited connective tissue disorder defined by characteristic facial features (acrogeria in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular
Germain, Dominique P
Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering
Ciarloni, L; Perrigouard, C; Lipsker, D; Cribier, B
Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of diseases involving genetic collagen fibre impairment. We describe a case of a patient presenting the rare type VIII, in which dermatitis ocre was associated with parodontal disease, and which was diagnosed late. A 29-year-old man consulted for a pretibial ulcer present for seven years, resulting from a post-traumatic haematoma that had failed to heal. In view of the longiliner morphology, it had previously been diagnosed as Marfan syndrome. Subsequently, edentation was observed as well as "alveolar bone fragility". Examination revealed a marfanoid morphotype, a pretibial ulcer set within long-standing bilateral dermatitis ocre and papyraceous scars, but no joint hyperlaxity or cutaneous hyperelasticity. The diagnosis was consequently corrected to EDS type VIII. Type VIII is a rare form of EDS, and the molecular mechanism is poorly understood. The involvement of parodontal connective tissue suggests impairment of collagen I and III proteins. It is important to identify this type of the disease since it involves parodontal disease for which early treatment is required in order to try to prevent edentation. The present case demonstrates the importance of diagnosis, which may be based upon appearance of bilateral dermatitis ocre from the age of 15 years associated with skin fragility. This sign is not part of the classical picture of Marfan syndrome, with which EDS type VIII is often confounded. Copyright 2009 Elsevier Masson SAS. All rights reserved.
Full Text Available We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patient's condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin, oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.
Pennings, Ronald J E; Fields, Randall R; Huygen, Patrick L M; Deutman, August F; Kimberling, William J; Cremers, Cor W R J
Clinical and genetic characteristics are presented of 2 patients from a Dutch Usher syndrome type III family who have a new homozygous USH3 gene mutation: 149-152delCAGG + insTGTCCAAT. One individual (IV:1) is profoundly hearing impaired and has normal vestibular function and retinitis punctata albescens (RPA). The other individual is also profoundly hearing impaired, but has well-developed speech, vestibular areflexia, and retinitis pigmentosa sine pigmento (RPSP). These findings suggest that Usher syndrome type III can be clinically misdiagnosed as either Usher type I or II; that Usher syndrome patients who are profoundly hearing impaired and have normal vestibular function should be tested for USH3 mutations; and that RPA and RPSP can occur as fundoscopic manifestations of pigmentary retinopathy in Usher syndrome.
Antunica, Antonela Gverović; Kastelan, Snjezana; Bućan, Kajo; Ivanković, Mira; Radman, Maja; Karaman, Ksenija
A case is presented of a very rare type of Usher's syndrome detected in a 30-year-old woman in her 28th week of pregnancy. She reported left eye visual impairment with a one-month history. She underwent standard ophthalmologic examination with additional procedures scheduled after childbirth, including fluorescein angiography, visual field (Goldman and Octopus) and electroretinography. Fundus examination revealed pallor of the optic disk, diffuse retinal blood vessel narrowing, no retinal pigmentation, left macular edema, vitreous liquefaction, and posterior vitreous detachment. Goldman perimetry showed narrowing of all isopters to 10 degrees, and Octopus perimetry showed peripheral decrease of retinal sensitivity. Electroretinography confirmed the diagnosis of retinitis pigmentosa sine pigmento. Upon collecting case history records, hearing disorders originating from childhood were discovered. To our knowledge, this type of retinitis in Usher's syndrome has been reported only once in the available literature.
Soker, Murat; Ayyildiz, Orhan; Isikdogan, Abdurrahman
Aase-Smith syndrome type II is a rare in childhood and there a few reported cases. Here, we report an 8-months-old boy with congenital red cell aplasia and triphalangeal thumbs. In addition to thumb anomalies. He presented with growth failure, hypertelorism and novel osseous radiologic abnormalities, large fontanelles and micrognathia as extraordinary. Some clinical symptoms had complete clinical remission with deflazacort treatment. (author)
Vialettes, Bernard; Dubois-Leonardon, Noémie
Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders associating several organ-specific autoimmune diseases. Their high prevalence is due to the fact that the main manifestations of APS-2, such as thyroidal autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are common diseases. APS-2 represents a clinical model that can serve to help unravel the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the clinician, especially in poorly symptomatic forms, and may require systematic screening based on measurement of autoantibodies and functional markers.
Kataoka, Satoshi; Hirose, Genjiro; Kosoegawa, Hiroshi; Oda, Rokuhei; Yoshioka, Akira
Two cases of brain stem type Neuro-Behcet's syndrome were evaluated by brain CT and Magnetic Resonance Imaging (Super-conducting type, 0.5 tesla) to correlate with the neurological findings. In the acute phase, low density area with peripheral enhancement effect and mass effect were seen at the brain stem in brain CT. MRI revealed a extensive high intensity signal area mainly involving the corticospinal tract in the meso-diencephalon as well as pons by T 2 weighted images (spin echo, TR = 1, 600 msec, TE = 90 msec) and the value of T 1 , T 2 , at the brain stem lesion were prolonged moderately. After high dose steroid treatment, the low density area in brain CT and high signal area in MRI were gradually reduced in its size. Peripheral enhancement effect in brain CT disappeared within 10 months in case 1, one month in the other case. In the chronic stage, the reduction of low density area and atrophy of brain stem were noted in brain CT. The lesion in chronic stage had low intensity in T 1 , T 2 weighted images and the T 1 , T 2 values at the lesion were mildly prolonged in MRI. Sequentially CT with enhancement and MRI examinations with T 1 , T 2 weighted images were useful to detect the lesion and to evaluate the activity, evolution of brain stem type Neuro-Behcet's syndrome. (author)
Pennings, R.J.E.; Fields, R.R.; Huygen, P.L.M.; Deutman, A.F.; Kimberling, W.J.; Cremers, C.W.R.J.
Clinical and genetic characteristics are presented of 2 patients from a Dutch Usher syndrome type III family who have a new homozygous USH3 gene mutation: 149-152delCAGG + insTGTCCAAT. One individual (IV:1) is profoundly hearing impaired and has normal vestibular function and retinitis punctata
Huang, L; Luiken, G P M; van Riemsdijk, I C; Petrij, F; Zandbergen, A A M; Dees, A
Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies characterised by renal salt wasting, hypokalaemic metabolic alkalosis, hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five types. Mutations in the KCNJ1 gene (classified as type II) usually cause the neonatal form of Bartter syndrome. We describe an adult patient with a homozygous KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter syndrome.
Yang, Jun; Wang, Le; Song, Hongman; Sokolov, Maxim
Usher syndrome is the most common deafness-blindness caused by genetic mutations. To date, three genes have been identified underlying the most prevalent form of Usher syndrome, the type II form (USH2). The proteins encoded by these genes are demonstrated to form a complex in vivo. This complex is localized mainly at the periciliary membrane complex in photoreceptors and the ankle-link of the stereocilia in hair cells. Many proteins have been found to interact with USH2 proteins in vitro, suggesting that they are potential additional components of this USH2 complex and that the genes encoding these proteins may be the candidate USH2 genes. However, further investigations are critical to establish their existence in the USH2 complex in vivo. Based on the predicted functional domains in USH2 proteins, their cellular localizations in photoreceptors and hair cells, the observed phenotypes in USH2 mutant mice, and the known knowledge about diseases similar to USH2, putative biological functions of the USH2 complex have been proposed. Finally, therapeutic approaches for this group of diseases are now being actively explored. PMID:22201796
Md. Ghulam Yusuf
Full Text Available In Bangladesh, there are very few studies about biopsy proven adult Nephrotic syndrome (NS with histological types and their clinical findings. To determine the histological types of glomerulonephritis (GN in adult NS and correlate them with the clinical presentations and biochemical parameters, we studied 100 biopsies in 87 patients who underwent ultrasonography- guided renal biopsy in Rangpur Medical College and Hospital from July 2010 to June 2012. The mean age of the patients was 32.8 ± 13.2 years; male was preponderance (72.4% and most of the patients (67.8% came from rural areas. Membranoproliferative GN (MPGN was the most common underlying cause that was found in 32 (36.8% patients followed by mesangial prolife- rative GN in 27 (31% patients, membranous GN in 16 (18.4% cases, minimal change disease in four (4.6% patients, diffuse proliferative GN in four (4.6% patients, focal segmental GN, and focal proliferative GN in two (2.4% patients each. High proteinuria level was found in minimal change disease, which was 7.59 ± 0.24 g/24 h (mean ± standard deviation. The most common symptoms were oliguria (92% and edema (86.2% followed by hematuria (dark urine (72.4% and hypertension (35.6%. MPGN was the most common histological type of adult NS in Rangpur.
Landau, Daniel; Gurevich, Evgenia; Sinai-Treiman, Levana; Shalev, Hannah
Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described. We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n = 14) or Barttin-deficient type IV BS (n = 20). Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6 ± 85.8 vs. 92.5 ± 48 pg/ml in BS-IV, p = 0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19 ± 0.71 vs. 0.01 ± 1.04 in BS-IV, p < 0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63 ± 1.25 vs. 4.36 ± 0.98, p = 0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group. PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.
Gollasch, Benjamin; Anistan, Yoland-Marie; Canaan-Kühl, Sima; Gollasch, Maik
Mutations in the ROMK1 potassium channel gene ( KCNJ1 ) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero , accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.
Plantinga, R.F.; Pennings, R.J.E.; Huygen, P.L.M.; Sankila, E.M.; Tuppurainen, K.; Kleemola, L.; Cremers, C.W.R.J.; Deutman, A.F.
PURPOSE: To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3) and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a (USH2a). METHODS: We carried out a retrospective study of 28 Finnish USH3 patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients.
Şuhani, Raluca Diana; Şuhani, Mihai Flaviu; Muntean, Alexandrina; Mesaroş, Michaela Florica; Badea, Mîndra Eugenia
Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the development of neural crest cells, caused by an altered cellular migration during the embryonic phase. That alteration causes an association of different abnormalities such as pigmentary disturbances of the hair, iris, skin, stria vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We report a case of a 14-year-old Romanian male, with a family history of Waardenburg syndrome (mother) and Usher syndrome (father - congenitally sensorineural hearing loss and retinal degeneration). The case particularities are: the correlation between malocclusion and Waardenburg syndrome due to hypoplastic alae nasi and also factors that produced hearing loss, which could be Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X) gene mutation.
Sadeghi, André M; Eriksson, Kristina; Kimberling, William J; Sjöström, Anders; Möller, Claes
To estimate the age at diagnosis of retinitis pigmentosa and to determine visual acuity deterioration, visual field impairment and the frequency of cataracts in Usher syndrome types 1 and 2. We carried out a retrospective study of 328 affected subjects with Usher syndrome types 1 and 2. Study subjects were divided into seven different age groups by decade. Data were analysed using descriptive statistics, general linear model anova and survival analysis. Retinitis pigmentosa was diagnosed significantly earlier in subjects with Usher syndrome type 1 than in those with type 2. Visual acuity was significantly more impaired in affected subjects with Usher syndrome type 1 than in those with type 2 from 50 years of age onwards. Survival analysis revealed a significant difference in visual field loss (type 2 subjects tending to be more impaired, while comparison indicated no significant differences between the groups in any of the other visual field categories. Cataract was found to be generally more common in Usher syndrome type 1 than type 2. Progressive loss of visual acuity and visual field begins to be substantial between the second and third decades of life in both Usher types. The rate of degeneration varies between individuals in both groups. The data are useful for the counselling of affected subjects with Usher syndrome types 1 and 2.
Kimberling, W J; Weston, M D; Möller, C; Davenport, S L; Shugart, Y Y; Priluck, I A; Martini, A; Milani, M; Smith, R J
Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.
Background: Metabolic syndrome is a cluster of three out of five conditions that are due to hyperinsulinemia: abdominal obesity, atherogenic dyslipidemia (high triglycerides and/or low HDL), elevated blood pressure, and elevated plasma glucose. The syndrome is highly prevalent in patients with type-2 diabetes mellitus ...
Background: The metabolic syndrome is a cluster of risk factors that is responsible for most of the excess cardiovascular morbidity amongst persons with type 2 Diabetes Mellitus (DM). The metabolic syndrome increases the risk for coronary heart disease and stroke by three-fold with a marked increase in cardiovascular ...
Sans, B; Calvas, P; Bazex, J
Waardenburg syndrome is an uncommon genetic disorder. Four clinical types are recognized. Three responsible genes have been identified (PAX 3: for type I syndrome, MITF and EDN3 for types II and IV respectively). We report the case of a patient with Waardenburg type I morphotype who had atypical neurological manifestations. Decisive elements for diagnosis were the presence of Waardenburg syndrome in the family and, in affected kin, a mutation causing a shift in PAX 3 gene reading. This case confirms the variability of Waardenburg signs within one family. The association of unusual neurological manifestations in the proband suggested that Vogt Koyanagi Harada disease may have been associated and may show some relationship with familial Waardenburg syndrome.
Agrawal, S; Subedi, K; Ray, P; Rayamajhi, A
Bartter syndrome Type III is a rare autosomal recessive disorder resulting from an inherited defect in the thick ascending limb of the loop of henle of the nephrons in kidney. The typical clinical manifestations in childhood are failure to thrive and recurrent episodes of vomiting. Typical laboratory findings which help in the diagnosis are hypokalemic metabolic alkalosis, hypomagnesemia and hypercalciuria. We report a case of Type III Bartter syndrome not responding to repeated conventional treatment of failure to thrive.
Iwasaki, Satoshi; Yoshimura, Hidekane; Takeichi, Norito; Satou, Hiroaki; Ishikawa, Kotaro; Kaga, Kimitaka; Kumakawa, Kozou; Nagai, Kyoko; Furuya, Nobuhiko; Ikezono, Tetsuo; Nakanishi, Hiroshi; Naitou, Yasu; Fukushima, Kunihiro; Tono, Tetsuya; Kimitsuki, Takashi; Nishio, Shinya; Takumi, Yutaka; Usami, Shinichi
Usher syndrome is an autosomal-recessive disorder that causes bilateral sensorineural hearing loss, retinitis pigmentosa (RP), and occasionally vestibular dysfunction. Usher syndrome types 1, 2, and 3 can be distinguished by differences in audiovestibular features. The objectives of this retrospective study were to evaluate 26 patients with Usher syndrome clinically. The 26 patients (male: 12 cases, female: 14 cases) with Usher syndrome, with a clinical diagnosis based on symptoms of bilateral sensorineural hearing loss and RP, had been registered from 13 hospitals as a multicenter study. We assessed the clinical history and performed audiovestibular and ophthalmologic examinations, and genetic testing. Eleven of the patients were classified as having Usher type 1 (38.5%), 6 with Usher type 2 (23.1%), and 9 with Usher type 3 (38.5%). However, many patients with atypical Usher type 1 (70%) and type 2 (83.3%) were found compared with Usher type 3 (10%). The conductive rate of vestibular examinations including the caloric test (50%) was low. There were many variations in the clinical symptoms in Usher syndrome patients, therefore the classification of Usher types 1, 2, and 3 has been complicated. We have proposed a flowchart for the diagnosis of Usher types 1, 2, and 3.
Rigoldi, Chiara; Galli, Manuela; Cimolin, Veronica; Camerota, Filippo; Celletti, Claudia; Tenore, Nunzio; Albertini, Giorgio
People suffering from Ehlers-Danlos syndrome (EDS) hypermobility type present a severe ligament laxity that results in difficulties in muscle force transmission. The same condition is present in people suffering from Down syndrome (DS) even if their clumsy movements are due to cerebral and cognitive impairments. The aim of this study was to…
den Hartog, Alexander W; Franken, Romy; Zwinderman, Aeilko H; Timmermans, Janneke; Scholte, Arthur J; van den Berg, Maarten P; de Waard, Vivian; Pals, Gerard; Mulder, Barbara J M; Groenink, Maarten
Aortic dissections involving the descending aorta are a major clinical problem in patients with Marfan syndrome. The purpose of this study was to identify clinical parameters associated with type B aortic dissection and to develop a risk model to predict type B aortic dissection in patients with Marfan syndrome. Patients with the diagnosis of Marfan syndrome and magnetic resonance imaging or computed tomographic imaging of the aorta were followed for a median of 6 years for the occurrence of type B dissection or the combined end point of type B aortic dissection, distal aortic surgery, and death. A model using various clinical parameters as well as genotyping was developed to predict the risk for type B dissection in patients with Marfan syndrome. Between 1998 and 2013, 54 type B aortic dissections occurred in 600 patients with Marfan syndrome (mean age 36 ± 14 years, 52% male). Independent variables associated with type B aortic dissection were prior prophylactic aortic surgery (hazard ratio: 2.1; 95% confidence interval: 1.2 to 3.8; p = 0.010) and a proximal descending aorta diameter ≥27 mm (hazard ratio: 2.2; 95% confidence interval: 1.1 to 4.3; p = 0.020). In the risk model, the 10-year occurrence of type B aortic dissection in low-, moderate-, and high-risk patients was 6%, 19%, and 34%, respectively. Angiotensin II receptor blocker therapy was associated with fewer type B aortic dissections (hazard ratio: 0.3; 95% confidence interval: 0.1 to 0.9; p = 0.030). Patients with Marfan syndrome with prior prophylactic aortic surgery are at substantial risk for type B aortic dissection, even when the descending aorta is only slightly dilated. Angiotensin II receptor blocker therapy may be protective in the prevention of type B aortic dissections. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Hromnats'ka, N M
To study dyslipidemia types in children with metabolic syndrome. From 1520 children of total population 155 children aged from 9 to 18 years were selected, who formed 2 groups: 1 group--85 children with metabolic syndrome, 2 group--54 children with normal body mass. Anthropometry, blood pressure measurement, estimation of total cholesterol, low density cholesterol, very low density cholesterol, high density cholesterol, tryglicerides in blood were done. The total cholesterol level was 1,1 times higher (p = 0.001), low density cholesterol 1,4 times higher (p = 0.001), very low density cholesterol 1,1 times higher (p= 0.015), tryglicerides 1,1 times higher (p = 0.020) in children with metabolic syndrome than in children of control group. In children with metabolic syndrome sensitively more often IIa, IV dislipidemia types and isolated hypercholesterolemia and less often IIb, III dislipidemia types and high density cholesterol isolated decrease were diagnosed. So children with metabolic syndrome were characterized by atherogenic types of dislipidemias which determine early atherosclerosis development. Children with metabolic syndrome must be examined on the lipid metabolism violation with the aim of its prevention and correction.
M. Cristina Digilio
Full Text Available Atrioventricular canal defect (AVCD is a common congenital heart defect (CHD, representing 7.4% of all cardiac malformations, considered secondary to an extracellular matrix anomaly. The AVCD is associated with extracardiac defects in about 75% of the cases. In this review we analyzed different syndromic AVCDs, in particular those associated with polydactyly disorders, which show remarkable genotype-phenotype correlations. Chromo - some imbalances more frequently associated with AVCD include Down syndrome, deletion 8p23 and deletion 3p25, while mendelian disorders include Noonan syndrome and related RASopathies, several polydactyly syndromes, CHARGE and 3C (cranio-cerebello-cardiac syndrome. The complete form of AVCD is prevalent in patients with chromosomal imbalances. Additional cardiac defects are found in patients affected by chromosomal imbalances different from Down syndrome. Left-sided obstructive lesions are prevalently found in patients with RASopathies. Patients with deletion 8p23 often display AVCD with tetralogy of Fallot or with pulmonary valve stenosis. Tetralogy of Fallot is the only additional cardiac defect found in patients with Down syndrome and AVCD. On the other hand, the association of AVCD and tetralogy of Fallot is also quite characteristic of CHARGE and 3C syndromes. Heterotaxia defects, including common atrium and anomalous pulmonary venous return, occur in patients with AVCD associated with polydactyly syndromes (Ellis-van Creveld, short rib polydactyly, oral-facial-digital, Bardet-Biedl, and Smith-Lemli-Opitz syndromes. The initial clinical evidence of anatomic similarities between AVCD and heterotaxia in polydactyly syndromes was corroborated and explained by experimental studies in transgenic mice. These investigations have suggested the involvement of the Sonic Hedgehog pathway in syndromes with postaxial polydactyly and heterotaxia, and ciliary dysfunction was detected as pathomechanism for these disorders
Kotb Abbass Metwalley
Full Text Available Kenny-Caffey syndrome type 1 (KCS1 (OMIM 244460 is a rare syndrome characterized by growth retardation, uniformly small slender long bones with medullary stenosis, thickened cortex of the long bones, hypocalcemia possibly with tetany at an early age and normal intelligence. The primary outcome of KCS1 is short stature. We present here an Egyptian girl aged 32 months with typical feature of KCS1.
Shimizu, Wataru; Moss, Arthur J.; Wilde, Arthur A. M.; Towbin, Jeffrey A.; Ackerman, Michael J.; January, Craig T.; Tester, David J.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Kaufman, Elizabeth S.; Hofman, Nynke; Noda, Takashi; Kamakura, Shiro; Miyamoto, Yoshihiro; Shah, Samit; Amin, Vinit; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott
Objectives The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Background Previous studies were limited by population size in their ability to examine phenotypic effect of
Simmonds, Jane V; Herbland, Anthony; Hakim, Alan; Ninis, Nelly; Lever, William; Aziz, Qasim; Cairns, Mindy
To explore exercise beliefs and behaviours of individuals with Joint Hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type and to explore patient experiences of physiotherapy. A cross sectional questionnaire survey design was used to collect quantitative and qualitative data from adult members of the Hypermobility Syndromes Association and Ehlers-Danlos Syndrome Support UK. Descriptive and inferential statistics were used to analyse the data. Qualitative data was analysed thematically. 946 questionnaires were returned and analysed. Participants who received exercise advice from a physiotherapist were 1.75 more likely to report high volumes of weekly exercise (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.30-2.36, p Ehlers-Danlos syndrome - hypermobility type in this survey. Implications for rehabilitation Exercise is a cornerstone of treatment for Ehlers-Danlos syndrome/Ehlers-Danlos syndrome - hypermobility type. Pain, fatigue and fear of injury are frequently reported barriers to exercise. Advice from physiotherapists may significantly influence exercise behaviour. Physiotherapists with condition specific knowledge and good verbal and non-verbal communication facilitate a positive therapeutic experience.
Krysiak, Robert; Okopień, Bogusław
Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract
Akturk, Halis Kaan; Yasa, Seda
Wolfram syndrome (WFS) is a rare autosomal recessive disease with non-autoimmune childhood onset insulin dependent diabetes and optic atrophy. WFS type 2 (WFS2) differs from WFS type 1 (WFS1) with upper intestinal ulcers, bleeding tendency and the lack ofdiabetes insipidus. Li-fespan is short due to related comorbidities. Only a few familieshave been reported with this syndrome with the CISD2 mutation. Here we report two siblings with a clinical diagnosis of WFS2, previously misdiagnosed with type 1 diabetes mellitus and diabetic retinopathy-related blindness. We report possible additional clinical and laboratory findings that have not been pre-viously reported, such as asymptomatic hypoparathyroidism, osteomalacia, growth hormone (GH) deficiency and hepatomegaly. Even though not a requirement for the diagnosis of WFS2 currently, our case series confirm hypogonadotropic hypogonadism to be also a feature of this syndrome, as reported before. © Polish Society for Pediatric Endocrinology and Diabetology.
Full Text Available Cardiorenal Syndrome Type 1 (CRS-1 is defined as an acute worsening of heart function leading to acute kidney injury and/or dysfunction. It is an important cause of hospitalization which affects the diagnosis as well as the prognosis and treatment of patients. The purpose of this paper is to analyze causes that lead to the development of cardiorenal syndrome type 1 and its clinical consequences, as well as to emphasize the clinical importance of its early detection. The clinical studies and professional papers dealing with etiopathogenesis, diagnosis and treatment of cardiorenal syndrome type 1, have been analyzed. The most important role in the occurrence of cardio renal syndrome type 1 is played by hemodynamic mechanisms, activation of neurohumoral systems, inflammation and imbalance between the production of reactive oxygen species (ROS and nitric oxide (NO. Diagnosis of cardiorenal syndrome type 1 involves biomarkers of acute renal injury among which the most important are: neutrophil gelatinaseassociated lipocalin (NGAL, cystatin C, kidney injury molecule 1 (KIM-1, liver-type fatty acid binding protein (L-FABP, IL-18 and the values of nitrogen compounds in serum. In addition to a pharmacological therapy, various modalities of extracorporeal ultrafiltration are applied in treatment of CRS-1, particularly if there is resistance to the use of diuretic therapy. As opposed to the experimental models, in clinical practice acute renal injury is often diagnosed late so that the measures taken do not give the expected results and the protective role shown in experimental conditions do not give the same results. For all these reasons, it is necessary to analyze the pathophysiology of renal impairment in cardiorenal syndrome as well as detect early indicators of kidney injury that could have clinical benefit and positive impact on reducing the cost of treatment.
Mazhar Müslüm Tuna
Full Text Available Neurofibromatosis (NF Type 1 (NF-1 is an autosomal dominant disease with a prevalence of about 1/3000. NF-1 is a neurocutaneous syndrome characterized by cafe au lait macules, neurofibroma, optic glioma, lisch nodules, and symptoms involving other systems. Noonan syndrome (NS is a clinically heterogeneous disorder predominantly characterized by dysmorphic facial features, congenital heart disease, proportionate post-natal short stature, neck abnormalities, and chest deformities. NF-NS is a very rare overlapping syndrome sharing many features of both syndromes. Coexistence of pheochromocytoma, which can be life-threatening if not treated properly, is also a very rare complication of this disorder. Here, we report a patient who was admitted with a mass in the right upper quadrant and was diagnosed with pheochromocytoma and NFNS. (The Medical Bulletin of Haseki 2014; 52: 227-31
Ahmed, N.; Ahmad, T.; Hussain, S.J.; Javed, M.
Background: Diabetes, Hypertension, Obesity and Ischaemic Heart Disease have become a problem of public health magnitude with substantial economic burden both in the developed as well as the developing countries. Obesity is quite frequent in Type 2 diabetics and also plays a central role in causing Metabolic Syndrome (MetS). Metabolic Syndrome significantly increases the incidence of cardiovascular complications. This study was done to determine the frequency of MetS in our Type 2 diabetic patients as most of the components of MetS can be modified and identifying/managing these at an early stage might be of considerable help in reducing cardiovascular complications. Methods: This cross-sectional study was done in Medical B and Medical A wards of Ayub Teaching Hospital, Abbottabad from Nov, 08 to April, 09. Type 2 Diabetic patients aged above 40 years who gave informed consent were included in the study. Data was collected through a structured proforma. Frequency of Metabolic Syndrome was estimated according to the IDF consensus worldwide definition of the MetS. Results: Of the 100 patients enrolled in this study 56 were females and 44 were males with a mean age of 59.9 years. Out of these 100 participants seventy six (76%) were diagnosed to have metabolic syndrome. Of the 56 females, forty eight (85.71%) were having metabolic syndrome while twenty eight (63.63%) of the 44 male participants were having the syndrome. The difference was statistically significant (p<0.05). Conclusion: Frequency of MetS was found to be significantly high in this study with female preponderance. All the components, except Hypertension were more frequent in females. Diabetic patients with metabolic syndrome need more aggressive approach in management so as to decrease the incidence of cardiovascular complications. (author)
Cheng, Jem L; Au, Jason S; Guzman, Juan C; Morillo, Carlos A; MacDonald, Maureen J
The cardiovascular profile of postural orthostatic tachycardia syndrome + Ehlers-Danlos syndrome hypermobility type (POTS + EDSIII) has not been described, despite suggestions that it plays a role in orthostatic intolerance. We studied nine individuals diagnosed with POTS + EDSIII and found that the arterial stiffness and cardiac profiles of patients with POTS + EDSIII were comparable to those of age- and sex-matched controls, suggesting an alternate explanation for orthostatic intolerance.
Reisser, Christoph F V; Kimberling, William J; Otterstedde, Christian R
Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.
with MRI every 3 months and the bone marrow oedema disappeared after 6 months. Introduction ... SA JOURNAL OF RADIOLOGY • August 2004. Reflex sympathetic dystrophy/complex regional pain syndrome, type 1 ... may be either trauma of external origin or iatrogenic, post surgery. In some patients particularly children ...
Frolke, J.P.M.; Dongen, R.T.M. van; Meent, H. van de
Complex regional pain syndrome type 1 (CRPS-1) was identified in the Netherlands more than 30 years ago, but since then the arguments supporting this diagnosis have become weaker. Incidence has decreased, it is often not possible to make a definite diagnosis, the pathophysiology remains unclear and
Perez, R.S.G.M.; Zollinger, P.E.; Dijkstra, P.U.; Thomassen-Hilgersom, I.L.; Zuurmond, W.W.A.; Rosenbrand, C.J.G.M.; Geerzen, J.H.B.
Background: Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I.Method: A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according
Perez, Roberto S.; Zollinger, Paul E.; Dijkstra, Pieter U.; Thomassen-Hilgersom, Ilona L.; Zuurmond, Wouter W.; Rosenbrand, Kitty C. J.; Geertzen, Jan H.
Background: Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I. Method: A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according
Kanika Singh Dhull
Full Text Available Oro-Facial Digital Syndrome (OFDS is a generic term for group of apparently distinctive genetic diseases that affect the development of the oral cavity, facial features, and digits. One of these is OFDS type I (OFDS-I which has rarely been reported in Asian countries. This is the case report of a 13 year old patient with OFDS type I who reported to the Department of Pedodontics and Preventive Dentistry, with the complaint of discolored upper front teeth.
Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke
Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weaknes...
Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S
Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients.
Nagel, Maria A; Choe, Alexander; Traktinskiy, Igor; Gilden, Don
Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later. 2015 BMJ Publishing Group Ltd.
V. I. Albanova
Full Text Available The Kindler syndrome is one of the types of hereditary epidermolysis bullosa with its onset related to mutations of the KIND1 gene. The authors describe a case of a family with three members suffering from this rare disease. All of these patients have typical clinical manifestations of the Kindler syndrome such as the formation of blisters on the skin and mucous membranes right after the birth, scarring with the formation of contractures, pseudosyndactyly, microstomia and ankyloglossia, progressive poikiloderma, photosensibility, affections of the gastrointestinal tract - dysphagia, esophagostenosis, stool disorders, dental pathology, phimosis vaginalis in women.
Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz
Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis.
Bowen, Jessica M; Sobey, Glenda J; Burrows, Nigel P; Colombi, Marina; Lavallee, Mark E; Malfait, Fransiska; Francomano, Clair A
Classical EDS is a heritable disorder of connective tissue. Patients are affected with joint hypermobility, skin hyperextensibilty, and skin fragility leading to atrophic scarring and significant bruising. These clinical features suggest consideration of the diagnosis which then needs to be confirmed, preferably by genetic testing. The most recent criteria for the diagnosis of EDS were devised in Villefranche in 1997. [Beighton et al. (1998); Am J Med Genet 77:31-37]. The aims set out in the Villefranche Criteria were: to enable diagnostic uniformity for clinical and research purposes, to understand the natural history of each subtype of EDS, to inform management and genetic counselling, and to identify potential areas of research. The authors recognized that the criteria would need updating, but viewed the Villefranche nosology as a good starting point. Since 1997, there have been major advances in the molecular understanding of classical EDS. Previous question marks over genetic heterogeneity have been largely surpassed by evidence that abnormalities in type V collagen are the cause. Advances in molecular testing have made it possible to identify the causative mutation in the majority of patients. This has aided the further clarification of this diagnosis. The aim of this literature review is to summarize the current knowledge and highlight areas for future research. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Sang Jin Kim
Full Text Available Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84, and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.
Full Text Available Bartter syndrome (BS type 1 (OMIM #601678 is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management.
Vergine, Gianluca; Fabbri, Elena; Pedini, Annalisa; Tedeschi, Silvana; Borsa, Niccolò
Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management.
Krahe, Anne Maree; Adams, Roger David; Nicholson, Leslie Lorenda
To assess the prevalence, severity and impact of fatigue on individuals with joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome - hypermobility type (EDS-HT) and establish potential determinants of fatigue severity in this population. Questionnaires on symptoms and signs related to fatigue, quality of life, mental health, physical activity participation and sleep quality were completed by people with JHS/EDS-HT recruited through two social media sites. Multiple regression analysis was performed to identify predictors of fatigue in this population. Significant fatigue was reported by 79.5% of the 117 participants. Multiple regression analysis identified five predictors of fatigue severity, four being potentially modifiable, accounting for 52.3% of the variance in reported fatigue scores. Predictors of fatigue severity were: the self-perceived extent of joint hypermobility, orthostatic dizziness related to heat and exercise, levels of participation in personal relationships and community, current levels of physical activity and dissatisfaction with the diagnostic process and management options provided for their condition. Fatigue is a significant symptom associated with JHS/EDS-HT. Assessment of individuals with this condition should include measures of fatigue severity to enable targeted management of potentially modifiable factors associated with fatigue severity. Implications for rehabilitation Fatigue is a significant symptom reported by individuals affected by joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type. Potentially modifiable features that contribute to fatigue severity in this population have been identified. Targeted management of these features may decrease the severity and impact of fatigue in joint hypermobility syndrome/Ehlers-Danlos syndrome - hypermobility type.
Wilde, Arthur A M; Moss, Arthur J; Kaufman, Elizabeth S
BACKGROUND: -Risk stratification in patients with type 3 long QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of ß-blocker therapy have not been studied previously in a large LQT3 population. METHODS: -The study population included 406 LQT3 patients with 51 different......-blocker therapy reduces this risk in females, but efficacy in males could not be conclusively determined due to low number of events....
Belloni, C.; Beluffi, G.
A case of perinatal lethal dwarfism is described: owing to its clinical, radiological and histologic features the case can be classified as SRP syndrome type III (Verma-Naumoff). On the basis of the radiological features and - particularly - of those of the growing cartilage, stress is laid on the importance of these studies for a proper classification of such rare and not completely known chondrodysplastic dwarfisms.
Belloni, C.; Beluffi, G.; Ospedale Maggiore, Lodi
A case of perinatal lethal dwarfism is described: owing to its clinical, radiological and histologic features the case can be classified as SRP syndrome type III (Verma-Naumoff). On the basis of the radiological features and - particularly - of those of the growing cartilage, stress is laid on the importance of these studies for a proper classification of such rare and not completely known chondrodysplastic dwarfisms. (orig.) [de
Rani, Alka; Pal, Nikhil; Azad, Raj Vardhan; Sharma, Yog Raj; Chandra, Parijat; Vikram Singh, Deependra
Retinal detachment is a rare complication in patients with retinitis pigmentosa. A case is reported of tractional retinal detachment in a patient with retinitis pigmentosa and sensorineural hearing loss, which was diagnosed as Usher syndrome type II. Because of the poor visual prognosis, the patient refused surgery in that eye. Tractional retinal detachment should be added to the differential diagnoses of visual loss in patients with retinitis pigmentosa.
Tinkle, Brad; Castori, Marco; Berglund, Britta; Cohen, Helen; Grahame, Rodney; Kazkaz, Hanadi; Levy, Howard
The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue. It has been described largely in those with musculoskeletal complaints including joint hypermobility, joint subluxations/dislocations, as well as skin and soft tissue manifestations. Many patients report activity-related pain and some go on to have daily pain. Two undifferentiated syndromes have been used to describe these manifestations-joint hypermobility syndrome and hEDS. Both are clinical diagnoses in the absence of other causation. Current medical literature further complicates differentiation and describes multiple associated symptoms and disorders. The current EDS nosology combines these two entities into the hypermobile type of EDS. Herein, we review and summarize the literature as a better clinical description of this type of connective tissue disorder. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Seys, Elsa; Andrini, Olga; Keck, Mathilde; Mansour-Hendili, Lamisse; Courand, Pierre-Yves; Simian, Christophe; Deschenes, Georges; Kwon, Theresa; Bertholet-Thomas, Aurélia; Bobrie, Guillaume; Borde, Jean Sébastien; Bourdat-Michel, Guylhène; Decramer, Stéphane; Cailliez, Mathilde; Krug, Pauline; Cozette, Paul; Delbet, Jean Daniel; Dubourg, Laurence; Chaveau, Dominique; Fila, Marc; Jourde-Chiche, Noémie; Knebelmann, Bertrand; Lavocat, Marie-Pierre; Lemoine, Sandrine; Djeddi, Djamal; Llanas, Brigitte; Louillet, Ferielle; Merieau, Elodie; Mileva, Maria; Mota-Vieira, Luisa; Mousson, Christiane; Nobili, François; Novo, Robert; Roussey-Kesler, Gwenaëlle; Vrillon, Isabelle; Walsh, Stephen B; Teulon, Jacques; Blanchard, Anne; Vargas-Poussou, Rosa
Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene ( CLCNKB ), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes. Copyright © 2017 by the American Society of Nephrology.
Flores-Guevara, Roberto; Renault, Francis; Loundon, Natalie; Marlin, Sandrine; Pelosse, Béatrice; Momtchilova, Martha; Auzoux-Chevé, Monique; Vermersch, Anne Isabelle; Richard, Pascal
Usher syndrome type 1 needs to be diagnosed at early age in order to timely manage speech therapy, cochlear implantation, and genetic counseling. Few data are available regarding electroretinographic testing before the age of six years. To describe electroretinographic changes in young children with Usher syndrome type 1. Retrospective study of fourteen patients. Age at first neurophysiologic testing was between 17 months and 5 years 4 months. Electroretinogram was performed using flash stimulation in mesopic conditions in the conscious child. Analysis was focused on the amplitudes and latencies of a- and b-waves. Whatever the age, an abnormal fundus was always confirmed with an absent electroretinogram. The youngest patient with absent electroretinogram was 17 month-old. When recorded on and after the 29th month of age, electroretinogram was absent in all cases, including 6 patients with normal fundus. In three patients a low-amplitude electroretinogram was present at first recording within the 26th and 27th months. Electroretinogram showed retinopathy in young children with Usher syndrome type 1, even in the absence of fundoscopic signs of retinal degeneration.
Full Text Available Joint hypermobility syndrome (JHS and Ehlers-Danlos syndrome, hypermobility type (EDS-HT are two clinically overlapping heritable connective tissue disorders strongly associating with pain, fatigue and other secondary aspects. No specific treatment exist for this syndrome and rehabilitation play a role in the management of these patients. The aim of this paper is to evaluate what are the evidence in literature about rehabilitation. Research was done using database PUBMED and consist in a revision of the studies published in the last 15 years. All studies agree to the beneficial role of the rehabilitative treatment and physical therapy but it’s necessary to add more further studies to establish a high quality, evidence-based physical therapy for this specific population.
Bashar S. Amr
Full Text Available Achalasia is a rare disease characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter to relax. The etiology of this disease remains unknown. Polyglandular autoimmune syndrome type II is a well-identified disease characterized by the occurrence of autoimmune Addison's disease in combination with autoimmune thyroid disease and/or type 1 diabetes mellitus. We report a case that suggests autoimmunity and immunogenicity as a probable contributing factor for association of these two rare disorders.
Erdem, Semiha Bahceci; Bag, Ozlem; Karkiner, Canan Sule Unsal; Korkmaz, Huseyin Anil; Can, Demet
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to “drug rash with eosinophilia and systemic symptoms syndrome” such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae. PMID:26862317
Plantinga, Rutger F; Pennings, Ronald J E; Huygen, Patrick L M; Sankila, Eeva-Marja; Tuppurainen, Kaija; Kleemola, Leenamaija; Cremers, Cor W R J; Deutman, August F
To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3) and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a (USH2a). We carried out a retrospective study of 28 Finnish USH3 patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS*) and functional vision score (FVS*) related to age were performed for all patients. The FFS* and FVS* were calculated using the isoptre V-4 test target instead of the usual III-4 target. Statistical tests relating to regression lines and Student's t-test were used to compare between USH3 patients and the other genetic subtypes of Usher syndrome. Cross-sectional analyses revealed significant deterioration in the FAS (1.3% per year), FFS* (1.4% per year) and FVS* (1.8% per year) with advancing age in the USH3 patient group. At a given age the USH3 patients showed significantly poorer visual field function than the USH2a patients. The rate of deterioration in visual function in Finnish USH3 patients was fairly similar to that in Dutch USH1b or USH2a patients. At a given age, visual field impairment in USH3 patients was similar to that in USH1b patients but poorer than in USH2a patients.
Zhang, Jin-liang; Zeng, Hui; Wang, Xian-bo
To study Chinese syndrome typing of acute hepatic failure (AHF) mice model by screening effective formulae. Lipoplysaccharides (LPS)/D-galactosamine (D-GaIN) was intraperitoneally injected to mice to establish the AHF mice model. Yinchenhao Decoction, Huanglian Jiedu Decoction, Buzhong Yiqi Decoction, and Xijiao Dihuang Decoction were administered to model mice respectively by gastrogavage. The behavior and the survival rate were monitored. The liver function and pathological changes of liver tissues were detected. In all the tested classic recipes, the survival rate was elevated from 10% to 60% by administration of Xijiao Dihuang Decoction. Five h after modeling, the serum alanine aminotransferase (ALT) level was (183.95 +/- 52.00) U/L, and aspartate aminotransferase (AST) (235.70 +/- 34.03) U/L in Xijiao Di-huang Decoction Group, lower than those of the model control group, but with insignificant difference (ALT: 213.32 +/- 71.93 U/L; AST: 299.48 +/- 70.56 U/L, both P > 0.05). Xijiao Dihuang Decoction could obviously alleviate the liver injury. Xijiao Dihuang Decoction was an effective formula for LPS/D-GaIN induced AHF model. According to syndrome typing through formula effect, heat toxin and blood stasis syndrome dominated in the LPS/D-GalN induced AHF mice model.
Sefsafi, Zakia; Hasbaoui, Brahim El; Kili, Amina; Agadr, Aomar; Khattab, Mohammed
Abstract Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign
Full Text Available A 70-year-old woman presented with burning pain and swelling over dorsum of right hand and small joints of the fingers, associated with redness, feeling of warmth, and stiffness of the fingers, with inability to bend the fingers since 2 months. The symptoms were progressively increasing in intensity for the past 1 month. There was no history of fever or trauma to the hand. Two months before her symptoms started, she had permanent pacemaker implanted for complete heart block with syncope. She was hypertensive and was on regular medication. Her X-ray of right hand showed decreased bone density (demineralisation, suggestive of osteopenia. A diagnosis of reflex sympathetic dystrophy syndrome or complex regional pain syndrome type I induced by pacemaker insertion was made. She was treated with amitriptyline and steroids, after which her symptoms improved dramatically.
Full Text Available Estimated incidence of Crigler-Najjar syndrome(CNS is 1 case per 1,000,000 births(1 million. The overall prevalence of CN syndrome is unknown, with only several hundred people reported to have this disease. It is interestingly very rare to encounter a pregnant adult women with congenital jaundice. Pregnancy in CN type II patients is a diagnostic and a therapeutic challenge because of the high risk of bilirubin encephalopathy with serious neurological damage as life-threatening complications for the fetus. To date 8 pregnancy outcome have been reported from 5 women and we report the6 woman with a successful 9 th pregnancy outcome. We have discussed detail history, presentation and management during pregnancy and care of the new born.
Andrés Ricardo Pérez-Riera
Full Text Available Congenital long QT syndrome type 3 (LQT3 is the third in frequency compared to the 15 forms known currently of congenital long QT syndrome (LQTS. Cardiac events are less frequent in LQT3 when compared with LQT1 and LQT2, but more likely to be lethal; the likelihood of dying during a cardiac event is 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. LQT3 is consequence of mutation of gene SCN5A which codes for the Nav1.5 Na+ channel α-subunit and electrocardiographically characterized by a tendency to bradycardia related to age, prolonged QT/QTc interval (mean QTc value 478 ± 52 ms, accentuated QT dispersion consequence of prolonged ST segment, late onset of T wave and frequent prominent U wave because of longer repolarization of the M cell across left ventricular wall.
Sakallı, Hale; Bucak, Hakan İbrahim
Pseudo-Bartter syndrome encompasses a heterogenous group of disorders similar to Bartter syndrome. Sometimes a few status may be nested, as in our case presented here. An 8-month-old boy was referred to our hospital with of intractable diarrhea, polyuria, persistent hypokalemia, abdominal distension and failure to thrive. He was born in the 34 6/7 gestational week (GW) to consanguineous parents. In the 30(th) GW polyhydramnios was verified by ultrasonography. The laboratory results showed hypokalemic-hypochloremic metabolic alkalosis, hyponatremia, and increased urinary loss of chloride, potassium and calcium. An audiogram test revealed complete sensorineural deafness. Ultrasonography revealed medullary nephrocalcinosis in both kidneys. Elevated plasma renin activity and aldosterone were found and a provisional diagnosis of type-IV neonatal Bartter syndrome was made. Treatment with indomethacin, spironolactone and additional intake of NaCl/KCl was initiated. Despite these therapies, the child's diarrhea persisted but serum potassium concentration normalized, and hypercalciuria and urine output reduced. After determining the high fecal chloride concentration, there was an immediate decompensation of the disease on indomethacin withdrawal, thus a diagnosis of type IV neonatal Bartter syndrome complicated with congenital chloride diarrhea was considered. Indomethacin, spironolactone and supplementary therapies with NaCl/KCl were continued, which resulted in the normalization of serum electrolytes as well as his physical development, but high contents of chloride in urine and faeces and nephrocalcinosis remains unchanged during 1-year follow-up. Because of the clinical and laboratory simulations between the various diseases that lead to hypokalemic-hypochloremic metabolic alkalosis, patients must be evaluated carefully.
Pakarinen, L; Tuppurainen, K; Laippala, P; Mäntyjärvi, M; Puhakka, H
Usher syndrome is a recessive hereditary disease group with clinical and genetical heterogeneity leading to handicapped hearing and visual loss until middle age. It is the most common cause for deaf-blindness. Three distinct phenotypes and five distinct genotypes are already known. In Finland the distribution of known Usher types is different than elsewhere. Usher syndrome type III (USH3) is common in Finland and it is thought to include 40% of patients. Progressive hearing loss is characteristic of USH3. Elsewhere USH3 has been regarded as a rarity covering only several percent of the whole Usher population. The aim of this paper is to describe, for the first time, the course of visual handicap and typical refractive errors in USH3 and compare it with other USH types. From a total patient sample consisting of 229 Finnish USH patients, 200 patients' visual findings were analyzed in a multicenter retrospective follow-up study. The average progress rate during a 10-year follow-up period in different USH types was similar. The essential progress occurred below the age of 40 and was continuous up to that age. Visual acuity dropped below 0.05 (severely impaired) at the age of 37 and the visual fields were of tubular shape without any peripheric islands at the average age of 30. Clinically significant hypermetropia with astigmatism seems to be a pathognomonic clinical sign of USH3.
Autoimmune polyglandular syndrome type 1 in a 12-year-old Ugandan girl. ... Journal of Endocrinology, Metabolism and Diabetes of South Africa ... Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasisectodermal dystrophy syndrome, is a very rare disorder of ...
Ozlem Marti Akgun
Full Text Available Griscelli syndrome (GS is a rare autosomal recessive genetic disorder characterized by variable immunodeficiency, partial albinism, abnormal accumulation of melanosomes in melanocytes, pigmentary dilution of the skin, and shiny silver-gray hair. GS has three types, with the first and second types caused by mutations in two genes being located at band 15q21: RAB27A and MYO5A. The expression of the third form of GS is restricted to the characteristic hypopigmentation of GS, and results from mutation in the gene that encodes melanophilin MLPH. It has also been shown that an identical phenotype can result from the deletion of the MYO5A F-exon. The aim of this case report is the presentation of oral and dental features and SEM images of the hair of a 12-year-old girl with GS type 3. [Arch Clin Exp Surg 2015; 4(3.000: 164-167
Wan, Liangcai; Guo, Menghe; Chen, Shuaijun; Liu, Shuangriu; Chen, Hao; Gong, Jian
To describe the multi-channel cochlear implantation in patients with Waardenburg syndrome including surgeries, pre and postoperative hearing assessments as well as outcomes of speech recognition. Multi-channel cochlear implantation surgeries have been performed in 12 cases with Waardenburg syndrome type II in our department from 2000 to 2008. All the patients received multi-channel cochlear implantation through transmastoid facial recess approach. The postoperative outcomes of 12 cases were compared with 12 cases with no inner ear malformation as a control group. The electrodes were totally inserted into the cochlear successfully, there was no facial paralysis and cerebrospinal fluid leakage occurred after operation. The hearing threshold in this series were similar to that of the normal cochlear implantation. After more than half a year of speech rehabilitation, the abilities of speech discrimination and spoken language of all the patients were improved compared with that of preoperation. Multi-channel cochlear implantation could be performed in the cases with Waardenburg syndrome, preoperative hearing and images assessments should be done.
Full Text Available Introduction. Autoimmune polyglandular syndrome type 2 is defined as adrenal insufficiency associated with autoimmune primary hypothyroidism and/or with autoimmune type 1 diabetes mellitus, but very rare with myasthenia gravis. Case report. We presented a case of an autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis. A 49-year-old female with symptoms of muscle weakness and low serum levels of cortisol and aldosterone was already diagnosed with primary adrenal insufficiency. Primary hypothyroidism was identified with low values of free thyroxine 4 (FT4 and raised values of thyroidstumulating hormone (TSH. The immune system as a cause of hypothyroidism was confirmed by the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia gravis was diagnosed on the basis of a typical clinical feature, positive diagnostic tests and an increased titre of antibodies against the acetylcholine receptors. It was not possible to confirm the immune nature of adrenal insufficiency by the presence of antibodies to 21- hydroxylase. The normal morphological finding of the adrenal glands was an indirect confirmation of the condition as well as the absence of other diseases that might have led to adrenal insufficiency and low levels of both serum cortisol and aldosterone. Hormone replacement therapy, anticholinergic therapy and corticosteroid therapy for myasthenia gravis improved the patient’s general state of health and muscle weakness. Conclusion. This case report indicates a need to examine each patient with an autoimmune disease carefully as this condition may be associated with another autoimmune diseases.
Hansen, Martin P; Matheis, Nina; Kahaly, George J
Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279
H. Otman S
Full Text Available A thirty six year-old African man, born in the Southern part of Libya, presented with congenital deafness and white forelock, variable-sized hypopigmented, depigmented patches and hyperpigmented islands within the areas of hypomelanosis affecting the upper parts of the trunk, both arms and forearms. The nasal root was hypertrophied, but there was a lack of lateral displacement of medial canthi. We report this case of Waardenburg syndrome type 2 (WS 2. As no treatment is available for patients with WS 2, prompt diagnosis and referral to a hearing specialist are crucial for the normal development of patients affected with this condition.
Full Text Available Griscelli syndrome (GS is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, RAB27A (GS2, and MLPH (GS3 genes, characterized by a common feature, partial albinism. The common variant of three, GS type 2, in addition, shows primary immunodeficiency which leads to recurrent infections and hemophagocytic lymphohistiocytosis. We, herewith, describe a case of GS type 2, in a 4-year-old male child who presented with chronic and recurrent fever, lymphadenopathy, hepatosplenomegaly, and secondary neurological deterioration; highlighting the cytological and histopathological features of lymph nodes. Hair shaft examination of the child confirmed the diagnosis.
Kiani, I.G.; Khan, A.N.; Yasir, S.; Baluch, U.T.
Background: Metabolic syndrome (MetS) is a cluster of coronary risk factors such as diabetes and pre-diabetes, abdominal obesity, high triglyceride (TG), low high density lipoprotein cholesterol (HDL-c) levels and high blood pressure (BP). It is estimated that around a quarter of the world adult population have MetS and they are twice as likely to die from it and three times as likely to have a coronary event or stroke compared with people without the syndrome. Methods: This observational descriptive study was conducted at the Department of General Medicine, Federal Government Polyclinic Islamabad. All type-2 diabetics presenting in the outpatient and inpatient department during 11 months between the ages of 30-80 were enrolled. They were interviewed, blood pressure, waist circumference, fasting blood glucose, and lipid profiles were checked. Results: Of the 300 patients 165 (55 percentage) were females and 135 (45 percentage) were males with mean age 52.47±11.24 years. The mean duration of Diabetes Mellitus was 7.38±3.85 years. Metabolic Syndrome was present in 83 percentage of the study population, 129 (43 percentage) were male and 171 (57 percentage) were female. The p-value was statistically significant on comparing the presence of the Metabolic Syndrome with waist circumference, serum triglyceride levels, and blood pressure as it was <0.05. The most commonly occurring finding was a decreased HDL-cholesterol in both genders. Conclusions: The MetS was present in 83 percentage of the diabetic population, mostly in females with decreased HDL-cholesterol being the most common in both genders. (author)
Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke
Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...
Baeza-Velasco, Carolina; Van den Bossche, Thomas; Grossin, Daniel; Hamonet, Claude
Joint Hypermobility Syndrome, also known as Ehlers-Danlos Syndrome Hypermobility Type (JHS/EDS-HT), is a heritable disorder of connective tissue, common but poorly known by the medical community. Although generalized joint hypermobility and fragility of tissues have been described as core features, recent research highlights the multisystemic nature of JHS/EDS-HT, which presents with a wide range of articular and extra-articular symptoms. Among these, gastrointestinal problems, temporomandibular disorders, and smell and taste abnormalities are common among those affected, having significant implications for eating. The present work reviews the literature linking JHS/EDS-HT and eating problems. Two illustrative case reports, in which JHS/EDS-HT manifestations contribute to developing and maintaining disturbed eating behaviors and significant weight loss, are presented.
Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk
This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail. PMID:24351514
Akal, Ali; Göncü, Tugba; Boyaci, Nurefsan; Yılmaz, Ömer Faruk
This study presents a case of an 8-year-old boy with iris heterochromia and anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2. An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia in our patient. In the systemic examination, a white forelock and vitiligo on the arms and body were observed and neurosensory hearing loss was revealed, for which the patient used hearing aids. Identification and typing of patients with WS is crucial to address neurosensory hearing loss, glaucoma and fundus changes. While it might be challenging to communicate with a patient with speech and hearing problems, visual acuity should be examined carefully and probable amblyopia should be identified. Anterior segment changes and signs of glaucoma should also be evaluated in detail.
Sadeghi, Mehdi; Cohn, Edward S; Kelly, William J; Kimberling, William J; Tranebjoerg, Lisbeth; Möller, Claes
The aim was to define the natural history of hearing loss in Usher syndrome type IIa compared to non-IIa. People with Usher syndrome type II show moderate-to-severe hearing loss, normal balance and retinitis pigmentosa. Several genes cause Usher syndrome type II. Our subjects formed two genetic groups: (1) subjects with Usher syndrome type IIa with a mutation and/or linkage to the Usher IIa gene; (2) subjects with the Usher II phenotype with no mutation and/or linkage to the Usher IIa gene. Four hundred and two audiograms of 80 Usher IIa subjects were compared with 435 audiograms of 87 non-IIa subjects. Serial audiograms with intervals of > or = 5 years were examined for progression in 109 individuals Those with Usher syndrome type IIa had significantly worse hearing thresholds than those with non-IIa Usher syndrome after the second decade. The hearing loss in Usher syndrome type IIa was found to be more progressive, and the progression started earlier than in non-IIa Usher syndrome. This suggests an auditory phenotype for Usher syndrome type IIa that is different from that of other types of Usher syndrome II. Thus, this is to our knowledge one of the first studies showing a genotype-phenotype auditory correlation.
Wang, Xueling; Lin, Xiao-Jiang; Tang, Xiangrong; Chai, Yong-Chuan; Yu, De-Hong; Chen, Dong-Ye; Wu, Hao
The purpose of this study was to identify the genetic causes of a family presenting with multiple symptoms overlapping Usher syndrome type II (USH2) and Waardenburg syndrome type IV (WS4). Targeted next-generation sequencing including the exon and flanking intron sequences of 79 deafness genes was performed on the proband. Co-segregation of the disease phenotype and the detected variants were confirmed in all family members by PCR amplification and Sanger sequencing. The affected members of this family had two different recessive disorders, USH2 and WS4. By targeted next-generation sequencing, we identified that USH2 was caused by a novel missense mutation, p.V4907D in GPR98; whereas WS4 due to p.V185M in EDNRB. This is the first report of homozygous p.V185M mutation in EDNRB in patient with WS4. This study reported a Chinese family with multiple independent and overlapping phenotypes. In condition, molecular level analysis was efficient to identify the causative variant p.V4907D in GPR98 and p.V185M in EDNRB, also was helpful to confirm the clinical diagnosis of USH2 and WS4. Copyright © 2017 Elsevier B.V. All rights reserved.
Akram, M.; Gillani, S.F.U.S.; Awais, S.M.
To determine the association between shoulder impingement and morphological characteristics of acromion and the role of sub-acromial injection of methylprednisolone in the short-term treatment for relieving pain and improve functional disability of these patients. Study Design: A descriptive study. Place and Duration of Study: Department of Orthopedic Surgery and Traumatology Unit-I (DOST-I), Mayo Hospital, Lahore, between November 2013 to June 2014. Methodology: All patients presented in OPD with shoulder pain were included as subjects and evaluated by clinical test and categorised using X-ray scapula Y-view. Patients with impingement syndrome were correlated with Bigliani types and offered intra-lesional injection into sub-acromial space with 2ml of xylocaine 2% and 40 mg of methylprednisolone using 22 gauge needle. The effectiveness was assessed in terms of relieving pain and good functional outcomes; and rotator cuff tear was clinically assessed among impingement positive patient. The pain was assessed using visual analogue score before and after the administration of the injection. Demographic variables for frequencies and their associations were analysed using SPSS version 20.0. Significance level was p<0.05. Among the 101 cases, there was no case of tear of rotator cuff tendon on clinical assessment. Majority of the patients (58.4%) were females with mean age of 31.38 +-1.13 years. Majority 57 (56.4%) of the patients had acromion type II (curved), which was the most common cause of shoulder impingement. Most had moderate pain. Thirty-four patients required intralesional steroid, which relieved the pain in 31 of them. Conclusion: Shoulder impingement syndrome without tear of rotator cuff tendon was found in younger age group between 40 to 45 years, which was relieved by intralesional corticosteroid administration. These patients had type II (curved) acromion, according to Bigliani classification. (author)
Raj, Prince; Birua, Hirendra
Congenital pouch colon (CPC) or short colon syndrome is a rare type of anorectal malformation(ARM). Type V is the rarest form of CPC. We present a 1-day-old male child with type V CPC with prune belly syndrome and congenital anterior urethrocutaneous fistula (CAUF).
Full Text Available Mark C Scheper,1,2 Janneke E de Vries,1–3 Jeanine Verbunt,3,4 Raoul HH Engelbert1,2 1School of Physiotherapy, Amsterdam University of Applied Sciences, Amsterdam, 2Department of Rehabilitation, Academic Medical Center, University of Amsterdam, Amsterdam, 3Department of Rehabilitation Medicine, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht; 4Adelante, Center of expertise in Rehabilitation and Audiology, Hoensbroek, the Netherlands Abstract: Generalized joint hypermobility (GJH is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers–Danlos syndrome. However, within the Ehlers–Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers–Danlos syndrome hypermobility type (EDS-HT. Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1 and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2. In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3. Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the
Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul Hh
Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH is also a clinical sign that is frequently present in hereditary diseases of the connective tissue, such as the Marfan syndrome, osteogenesis imperfecta, and the Ehlers-Danlos syndrome. However, within the Ehlers-Danlos spectrum, a similar subcategory of patients having similar clinical features as HMS but lacking a specific genetic profile was identified: Ehlers-Danlos syndrome hypermobility type (EDS-HT). Researchers and clinicians have struggled for decades with the highly diverse clinical presentation within the HMS and EDS-HT phenotypes (Challenge 1) and the lack of understanding of the pathological mechanisms that underlie the development of pain and its persistence (Challenge 2). In addition, within the HMS/EDS-HT phenotype, there is a high prevalence of psychosocial factors, which again presents a difficult issue that needs to be addressed (Challenge 3). Despite recent scientific advances, many obstacles for clinical care and research still remain. To gain further insight into the phenotype of HMS/EDS-HT and its mechanisms, clearer descriptions of these populations should be made available. Future research and clinical care should revise and create consensus on the diagnostic criteria for HMS/EDS-HT (Solution 1), account for clinical heterogeneity by the classification of subtypes within the HMS/EDS-HT spectrum (Solution 2), and create a clinical core set (Solution 3).
Autosomal Recessive Polycystic Kidney Disease; Congenital Hepatic Fibrosis; Caroli's Disease; Polycystic Kidney Disease; Joubert Syndrome; Cerebro-Oculo-Renal Syndromes; COACH Syndrome; Senior-Loken Syndrome; Dekaban-Arima Syndrome; Cogan Oculomotor Apraxia; Nephronophthisis; Bardet-Biedl Syndrome; Alstrom Syndrome; Oral-Facial-Digital Syndrome
Ana Rosa Rincón-Sánchez
Full Text Available Ehlers-Danlos syndrome (EDS is a heterogeneous group of heritable connective tissue disorders whose primary clinical features include soft and extensible skin, articular hypermobility and tissue fragility. EDS type VIIC or ‘human dermatosparaxis’ is an autosomal recessive disease characterized by severe skin fragility and sagging redundant skin (major criteria with a soft, doughy texture, easy bruising, premature rupture of fetal membranes and large hernias (minor criteria. Dermatosparaxis (meaning ‘tearing of skin’, which has been described in several non-human species, is a disorder of the connective tissue resulting from a deficiency of the enzyme that cleaves the registration peptide off the N-terminal end of collagen after it has been secreted from fibroblasts. We describe a Mexican case from consanguineous parents with all the phenotypical characteristics previously described, plus skeletal abnormalities.
Rossor, Thomas; Lim, Ming; VanDenEshof, Kirandeep; Gringras, Paul
Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep. NT1 is linked to hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually associated with increased rates of overweight and obesity, and sometimes with increases in overnight blood pressure and increased rates of hypoventilation with raised CO 2 levels overnight. Many of these are predisposing factors for pseudotumor cerebri syndrome (PTCS). We present a case of a young girl with both NT1 and PTCS that responded well to treatment with acetazolamide after early identification, with improvement of headache and resolution of hypoventilation. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Alice D. Chang
Full Text Available We studied a 14 year-old boy with partial DiGeorge syndrome (DGS, status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT. Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF, and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF. This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.
Sun, Mingran; Ning, Jing; Xu, Weihong; Zhang, Han; Zhao, Kaishu; Li, Wenfu; Li, Guiying; Li, Shibo
Bartter syndrome (BS) type 1 is an autosomal recessive kidney disorder caused by loss‑of‑function mutations in the solute carrier family 12 member 1 (SLC12A1) gene. To date, 72 BS type 1 patients harboring SLC12A1 mutations have been documented. Of these 144 alleles studied, 68 different disease‑causing mutations have been detected in 129 alleles, and no mutation was detected in the remaining 15 alleles. The mutation types included missense/nonsense mutations, splicing mutations and small insertions and deletions ranging from 1 to 4 nucleotides. A large deletion encompassing a whole exon in the SLC12A1 gene has not yet been reported. The current study initially identified an undocumented homozygous frameshift mutation (c.1833delT) by Sanger sequencing analysis of a single infant with BS type 1. However, in a subsequent analysis, the mutation was detected only in the father's DNA. Upon further investigation using a next‑generation sequencing approach, a deletion in exons 14 and 15 in both the patient and patient's mother was detected. The deletion was subsequently confirmed by use of a long‑range polymerase chain reaction and was determined to be 3.16 kb in size based on sequencing of the junction fragment. The results of the present study demonstrated that pathogenic variants of SLC12A1 are heterogeneous. Large deletions appear to serve an etiological role in BS type 1, and may be more prevalent than previously thought.
Braunlin, Elizabeth; Steinberger, Julia; DeFor, Todd; Orchard, Paul; Kelly, Aaron S
Hematopoietic cell transplantation is a life-saving procedure, but one associated with increasing long-term cardiovascular risk requiring frequent long-term follow-up. This therapy has significantly lengthened survival in mucopolysaccharidosis type IH (Hurler syndrome), a disease with known coronary artery involvement. Metabolic syndrome-a constellation of central obesity, high blood pressure, low high-density lipoprotein cholesterol, elevated triglycerides, and fasting blood glucose-is associated with increased cardiovascular risk, and occurs when any 3 or more of these 5 components is present within a single individual. The incidence of metabolic syndrome and its components is poorly defined after transplantation for Hurler syndrome. Chart review of all long-term survivors of hematopoietic cell transplantation for Hurler syndrome ≥9 years of age for factors comprising the metabolic syndrome: obesity, high blood pressure, low high-density lipoprotein cholesterol, elevated triglycerides, and fasting blood glucose. Sixty-three patients were evaluated, 20 of whom had components of the metabolic syndrome available for review. There was no significant difference in age at transplantation, sex, number of transplants, pretransplant radiation, or percent engraftment between those with and without these data. Median follow-up after transplantation for the 20 patients with data was 14.3 years. Only 1 (5%) patient of this group fulfilled the criteria for metabolic syndrome. Fifty-three percent of the patients had 1 or more components of metabolic syndrome: the most common was high blood pressure occurring in 40%. Metabolic syndrome is uncommon in this cohort of long-term survivors of hematopoietic cell transplantation for Hurler syndrome but almost half of the patients had 1 or more components of the syndrome, with high blood pressure being the most common. Further studies are needed to develop guidelines in this diagnosis as well as other nonmalignant diseases of children
Ogbera Anthonia O
Full Text Available Abstract Background Elevated serum uric acid levels (SUA have been associated with an increased risk of cardiovascular diseases and the metabolic syndrome (MetS and are often reported to be higher in females than in males. The aim of this report is to determine the prevalence and clinical correlates of hyperuricaemia and also to evaluate associations with the MetS in people with type 2 diabetes mellitus (DM. Methods This was a cross-sectional study conducted in people with type 2 DM in Lagos, Nigeria. Hyperuricaemia was defined by cut-off values of > 7 mg/dl for men and > 6 mg/dl for women. The diagnosis of MetS was made using the new definition by the American Heart Association and other related bodies. Clinical and biochemical parameters were compared between subjects with hyperuricaemia and normouricaemia. Statistical analysis included usage of Student's t test, Pearson correlation coefficients, multivariate regression analysis and chi square. Results 601 patients with type 2 DM aged between 34-91 years were recruited for the study. The prevalence rates of hyperuricaemia and the MetS were 25% and 60% respectively. The frequency of occurrence of hyperuricaemia was comparable in both genders (59% vs 41%, p = 0.3. Although, the prevalence of the MetS in subjects with hyperuricaemia and normouricaemia was comparable (61 vs 56%, p = 0.1, a higher proportion of hyperuricaemic subjects had 3 or more components of the Mets compared with normouricaemic subjects. Possible predictors of hyperuricaemia include central obesity, smoking and elevated serum triglycerides (TG. SUA levels were found to be positively and significantly associated with serum TG (r = 0.2, p = 0.0001 and total cholesterol (r = 13, p = 0.001. Conclusion The prevalence of hyperuricaemia in subjects with type 2 DM is comparable in both genders and possible predictors of hyperuricaemia are potentially modifiable. SUA is positively and significantly associated with serum TG and total
Bujakowska, Kinga M; Consugar, Mark; Place, Emily; Harper, Shyana; Lena, Jaclyn; Taub, Daniel G; White, Joseph; Navarro-Gomez, Daniel; Weigel DiFranco, Carol; Farkas, Michael H; Gai, Xiaowu; Berson, Eliot L; Pierce, Eric A
Patients with Usher syndrome type I (USH1) have retinitis pigmentosa, profound congenital hearing loss, and vestibular ataxia. This syndrome is currently thought to be associated with at least six genes, which are encoded by over 180 exons. Here, we present the use of state-of-the-art techniques in the molecular diagnosis of a cohort of 47 USH1 probands. The cohort was studied with selective exon capture and next-generation sequencing of currently known inherited retinal degeneration genes, comparative genomic hybridization, and Sanger sequencing of new USH1 exons identified by human retinal transcriptome analysis. With this approach, we were able to genetically solve 14 of the 47 probands by confirming the biallelic inheritance of mutations. We detected two likely pathogenic variants in an additional 19 patients, for whom family members were not available for cosegregation analysis to confirm biallelic inheritance. Ten patients, in addition to primary disease-causing mutations, carried rare likely pathogenic USH1 alleles or variants in other genes associated with deaf-blindness, which may influence disease phenotype. Twenty-one of the identified mutations were novel among the 33 definite or likely solved patients. Here, we also present a clinical description of the studied cohort at their initial visits. We found a remarkable genetic heterogeneity in the studied USH1 cohort with multiplicity of mutations, of which many were novel. No obvious influence of genotype on phenotype was found, possibly due to small sample sizes of the genotypes under study. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Full Text Available The treatment of patients with complex regional pain syndrome (CRPS type 1 is challenging and unpredictable as the condition presents with vascular and neuropathic symptoms after nil or even minor injury to a peripheral nerve. The condition is one of a pain and motor dysfunction. The pathophysiology is not well understood and the relief of symptoms may change from being sympathetically mediated to sympathetically independent during the course of the disease. At any stage physiotherapy has been advocated as the corner stone and most important aspect of treatment in the rehabilitation of these individuals but unfortunately it has been difficult to execute when pain is exacerbated due to allodynia (unbearable to touch or move and hyperalgesia. Best results have been obtained if the patients are recognised and treated in the early or acute phase and it has been found that through careful assessment and analysis these patients can be recognised by previous events that have occurred in their initial case history. The treatment in the acute stage with physiotherapy modalities such as electrical stimulation and acupuncture will produce an early cessation of the symptoms and prevention of the disease developing into the fully blown CRPS type 1 with irreversible and possibly atrophic consequences. Case histories have been presented that illustrate these important aspects and demonstrate the value of early and the appropriate physiotherapy that may be more successful than other pharmacological and physical interventions in this disease.
Full Text Available Complex regional pain syndrome (CPRS, type 1 is a pain disorder that develops unpredictably and can follow a minor injury. A 12-year-old boy presented with severe pain in the feet and could not walk or stand weight bearing. Normal X-rays showed osteopenic changes and radiolucent lines, which appeared to be stress fractures. Three-phase bone scintigraphy showed no uptake in the left lower leg on the blood pool phase or on the immediate or delayed images. This indicated typical CPRS type 1 in children. The uptake in the right foot was increased and the stress fracture and other illness could not be differentiated. Computed tomography was done to exclude stress fractures. Only osteopenic changes in both calcaneus bones were found and there was no evidence of cortical stress fractures. Magnetic resonance images revealed oedema in the calcaneus and talus bones of both feet. The patient received epidural narcotic infusion with sympathetic blockage for 1 week combined with extensive physiotherapy. The blood pool phase of the bone scan became normal within 2 weeks, and increased uptake in both feet was noticed. The patient was followed up with MRI every 3 months and the bone marrow oedema disappeared after 6 months.
Domenick, Natalie; Cho, Jae S; Abu Hamad, Ghassan; Makaroun, Michel S; Chaer, Rabih A
Patients with vascular type Ehler-Danlos syndrome can develop aneurysms in unusual locations. We describe the case of a 33-year-old woman with vascular type Ehlers-Danlos syndrome who developed metachronous tibial artery aneurysms that were sequentially treated with endovascular means. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Bonneau, D; Raymond, F; Kremer, C; Klossek, J M; Kaplan, J; Patte, F
Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucociliary clearance in two sibs and we suggest Usher syndrome type I could be a primary ciliary disorder.
Westland, Rik; Hack, Wilfried W; van der Horst, Henricus J R; Uittenbogaard, Lukas B; van Hagen, Johanna M; van der Valk, Paul; Kamsteeg, Erik J; van den Heuvel, Lambert P; van Wijk, Joanna A E
Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 years of life, known as classic Bartter syndrome. However, in rare cases Bartter syndrome Type III has an antenatal presentation with polyhydramnios, premature delivery and severe dehydration in the first weeks of life. Associations between congenital anomalies of the kidney and urinary tract and Bartter syndrome are extremely rare. This case report presents a girl with Bartter syndrome Type III due to a homozygous CLCNKB mutation and bilateral congenital anomalies of the kidney and urinary tract. In addition, we describe the antenatal presentation as well as its perinatal management.
Ni, Christina; Zhang, Deming; Beyer, Lisa A; Halsey, Karin E; Fukui, Hideto; Raphael, Yehoash; Dolan, David F; Hornyak, Thomas J
The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. © 2012 John Wiley & Sons A/S.
Tsilou, Ekaterini T; Rubin, Benjamin I; Caruso, Rafael C; Reed, George F; Pikus, Anita; Hejtmancik, James F; Iwata, Fumino; Redman, Joy B; Kaiser-Kupfer, Muriel I
Usher syndrome types I and II are clinical syndromes with substantial genetic and clinical heterogeneity. We undertook the current study in order to identify ocular symptoms and signs that could differentiate between the two types. Sixty-seven patients with Usher syndrome were evaluated. Based on audiologic and vestibular findings, patients were classified as either Usher type I or II. The severity of the ocular signs and symptoms present in each type were compared. Visual acuity, visual field area, electroretinographic amplitude, incidence of cataract and macular lesions were not significantly different between Usher types I and II. However, the ages when night blindness was perceived and retinitis pigmentosa was diagnosed differed significantly between the two types. There seems to be some overlap between types I and II of Usher syndrome in regard to the ophthalmologic findings. However, night blindness appears earlier in Usher type I (although the difference in age of appearance appears to be less dramatic than previously assumed). Molecular elucidation of Usher syndrome may serve as a key to understanding these differences and, perhaps, provide a better tool for use in clinical diagnosis, prognosis and genetic counseling.
Full Text Available Lattice corneal dystrophy gelsolin type was first described in 1969 by Jouko Meretoja, a Finnish ophthalmologist. It is caused by an autosomal dominant mutation in gelsolin gene resulting in unstable protein fragments and amyloid deposition in various organs. The age of onset is usually after the third decade of life and typical diagnostic triad includes progressive bilateral facial paralysis, loose skin, and lattice corneal dystrophy. We report a case of a 53-year-old female patient referred to our Department of Ophthalmology by severe dry eye and incomplete eyelid closure. She had severe bilateral facial paresis, significant orbicularis, and perioral sagging as well as hypoesthesia of extremities and was diagnosed with Meretoja’s syndrome at the age of 50, confirmed by the presence of gelsolin mutation. At our observation she had bilateral diminished tear film break-up time and Schirmer test, diffuse keratitis, corneal opacification, and neovascularization in the left eye. She was treated with preservative-free lubricants and topical cyclosporine, associated with nocturnal complete occlusion of both eyes, and underwent placement of lacrimal punctal plugs. Ocular symptoms are the first to appear and our role as ophthalmologists is essential for the diagnosis, treatment, and monitoring of ocular alterations in these patients.
Proust-Lemoine, Emmanuelle; Guyot, Sylvie
Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Thomassen-Hilgersom Ilona L
Full Text Available Abstract Background Treatment of complex regional pain syndrome type I (CRPS-I is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I. Method A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment. Results For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I. Conclusions Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines.
Ghibellini, Giulia; Brancati, Francesco; Castori, Marco
In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. © 2015 Wiley Periodicals, Inc.
Konala, Praveen; Cassar-Pullicino, Victor N. [The Robert Jones and Agnes Hunt Orthopaedic Hospital, Department of Radiology, Oswestry (United Kingdom); Kiely, Nigel [The Robert Jones and Agnes Hunt Orthopaedic Hospital, Department of Orthopaedic Surgery, Oswestry (United Kingdom); Noakes, Charlotte [Oxford University Hospital, The Oxford Genetics Laboratories, Oxford (United Kingdom); Blair, Edward [Oxford University Hospital, Department of Clinical Genetics, Oxford (United Kingdom)
Trichorhinophalangeal syndrome type II is a rare genetic disorder with the few published case reports mainly reporting the radiographic skeletal manifestations. There are no published imaging reports of long bone cysts involving multiple bones in this condition. We report a unique case of bone cysts involving multiple long bones detected with MRI in a patient with trichorhinophalangeal syndrome type II complicated by a subsequent pathological fracture. It is possible that the bone cysts are a previously undescribed feature of this syndrome; however, the evidence is insufficient to establish a definite association. Chromosomal abnormality identified in this patient is consistent with trichorhinophalangeal syndrome type II with no unusual features. Although the nature of these bone cysts is unclear, they are one of the causes of the known increased fracture risk observed in this syndrome. (orig.)
Voermans, N.C.; Alfen, N. van; Pillen, S.; Lammens, M.M.Y.; Schalkwijk, J.; Zwarts, M.J.; Rooij, I.A.L.M. van; Hamel, B.C.J.; Engelen, B.G.M. van
OBJECTIVE: Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Muscle involvement is plausible based on recently discovered interactions between
DM), there is a multiple set of risk factors that commonly appear together forming what is now known as the 'Metabolic Syndrome' (MS). This 'clustering' of metabolic abnormalities that occur in the same individual appear to confer substantial ...
Manna, R; Modugno, I; Pala, M A; Caputo, S; Caradonna, E; Greco, A V
Ehlers-Danlos syndrome is currently regarded as a connective tissue dysplasia. Its genetic, biochemical, histological and clinical features are described, together with a personal case in a patient who presented the fundamental symptoms, plus polydactyly and bifid urethra. This association had not been hitherto reported in the literature. The case itself is classed as Ehlers-Danlos syndrome type V.
Dec 4, 2014 ... Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 1985713834, Iran. [Kahrizi K. ... Usher syndrome (USH) is an autosomal recessive disease .... missense variants on the protein structures, pathogen severity .... genes to a Spanish Usher syndrome type 2 cohort.
Full Text Available Introduction. The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls.
Shafaei, Azam; Marjani, Abdoljalal; Khoshnia, Masoud
The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls. The study included 60 patients with type 2 diabetes and 30 healthy individuals as control groups. Biochemical parameters and progranulin levels were determined. Subjects with metabolic syndrome showed significantly higher levels of triglyceride, waist circumference, BMI, systolic and diastolic blood pressure than subjects without metabolic syndrome and the control groups, while HDL-cholesterol level was significantly lower in subjects with metabolic syndrome. Fasting blood sugar was significantly higher in type 2 diabetic patients than in the control groups. Serum level of progranulin was slightly increased in subjects with metabolic syndrome. Serum progranulin level had no significant relationship with metabolic syndrome components. Serum progranulin was also not dependent on cardiometabolic risk factors for subjects with metabolic syndrome, but it could be considered for the management of type 2 diabetes mellitus. Further studies are recommended to explain the effect of progranulin on the pathogenesis of metabolic risk factors.
Meeths, Marie; Bryceson, Yenan T; Rudd, Eva
Griscelli syndrome type 2 (GS2) is an autosomal-recessive immunodeficiency caused by mutations in RAB27A, clinically characterized by partial albinism and haemophagocytic lymphohistocytosis (HLH). We evaluated the frequency of RAB27A mutations in 21 unrelated patients with haemophagocytic syndromes...
Marjani, A.; Mojerloo, M.
Objective: To assess the prevalence of the metabolic syndrome in subjects diagnosed with Type 2 diabetes in Gorgan, Iran. Methods: Data were collected from 200 subjects with Type 2 diabetes mellitus and they were categorized as with or without the metabolic syndrome. Metabolic syndrome was diagnosed using Adult Treatment Panel-III (ATP-III) guidelines. Results: The overall metabolic syndrome prevalence was 51.50%. The mean age of all the subjects was 53.65+-9.50 years. There were 122 females and 78 males of whom 65 females and 38 males had the metabolic syndrome. The mean duration of diabetes was 7.70+-1.29 years. Mean triglycerides were 185.15+-56.63 mg/dl, and fasting blood glucose 153 +-19.6 mg/dl. These levels were significantly higher in the subjects with type-2 diabetes with metabolic syndrome, but the mean HDL-cholesterol was 37.96+-5.09 mg/dl and this was lower (p< 0.001). Female and male subjects with metabolic syndrome had significantly longer (except HDL-cholesterol) duration of diabetes, higher Triglyceride, and fasting blood glucose levels (p < 0.001, p < 0.05). Conclusion: This study showed a high prevalence of the metabolic syndrome in subjects with type 2 diabetes. Females were more affected than males. (author)
Westland, R.; Hack, W.W.; van der Horst, H.J.; Uittenbogaard, L.B.; van Hagen, J.M.; van der Valk, P.; Kamsteeg, E.J.; Heuvel, L.P.W.J. van den; van Wijk, J.A.
Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2
Pardono, Eliete; van Bever, Yolande; van den Ende, Jenneke; Havrenne, Poti C; Iughetti, Paula; Maestrelli, Sylvia R P; Costa F, Orozimbo; Richieri-Costa, Antonio; Frota-Pessoa, Oswaldo; Otto, Paulo A
Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the
Full Text Available Stickler syndrome or hereditary progressive arthroophthalmopathy is a heterogeneous group of collagen tissue disorders, characterized by orofacial features, ophthalmological features (high myopia, vitreoretinal degeneration, retinal detachment, and presenile cataracts, hearing impairment, mild spondyloepiphyseal dysplasia, and/or early onset arthritis. Stickler syndrome type I (ocular form is caused by mutation in the COL2A1 gene. Ptosis and uveitis are relatively rare ophthalmological manifestations of this syndrome. We report an Indian boy having 2710C>T mutation in COL2A1 gene demonstrating short stature, ptosis, and uveitis with Stickler syndrome.
Reiners, J.; Wijk, E. van; Marker, T.; Zimmermann, U.; Jurgens, K.; Brinke, H. te; Overlack, N.; Roepman, R.; Knipper, M.; Kremer, J.M.J.; Wolfrum, U.
Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. USH is clinically and genetically heterogeneous with at least 11 chromosomal loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the different USH types exhibit almost the same phenotype in human,
Rong, Weining; Chen, Xue; Zhao, Kanxing; Liu, Yani; Liu, Xiaoxing; Ha, Shaoping; Liu, Wenzhou; Kang, Xiaoli; Sheng, Xunlun; Zhao, Chen
Usher syndrome (USH) is a group of disorders manifested as retinitis pigmentosa and bilateral sensorineural hearing loss, with or without vestibular dysfunction. Here, we recruited three Chinese families affected with autosomal recessive USH for detailed clinical evaluations and for mutation screening in the genes associated with inherited retinal diseases. Using targeted next-generation sequencing (NGS) approach, three new alleles and one known mutation in MYO7A gene were identified in the three families. In two families with USH type 1, novel homozygous frameshift variant p.Pro194Hisfs*13 and recurrent missense variant p.Thr165Met were demonstrated as the causative mutations respectively. Crystal structural analysis denoted that p.Thr165Met would very likely change the tertiary structure of the protein encoded by MYO7A. In another family affected with USH type 2, novel biallelic mutations in MYO7A, c.[1343+1G>A];[2837T>G] or p.[?];[Met946Arg], were identified with clinical significance. Because MYO7A, to our knowledge, has rarely been correlated with USH type 2, our findings therefore reveal distinguished clinical phenotypes associated with MYO7A. We also conclude that targeted NGS is an effective approach for genetic diagnosis for USH, which can further provide better understanding of genotype-phenotype relationship of the disease.
Full Text Available Usher syndrome (USH is a group of disorders manifested as retinitis pigmentosa and bilateral sensorineural hearing loss, with or without vestibular dysfunction. Here, we recruited three Chinese families affected with autosomal recessive USH for detailed clinical evaluations and for mutation screening in the genes associated with inherited retinal diseases. Using targeted next-generation sequencing (NGS approach, three new alleles and one known mutation in MYO7A gene were identified in the three families. In two families with USH type 1, novel homozygous frameshift variant p.Pro194Hisfs*13 and recurrent missense variant p.Thr165Met were demonstrated as the causative mutations respectively. Crystal structural analysis denoted that p.Thr165Met would very likely change the tertiary structure of the protein encoded by MYO7A. In another family affected with USH type 2, novel biallelic mutations in MYO7A, c.[1343+1G>A];[2837T>G] or p.[?];[Met946Arg], were identified with clinical significance. Because MYO7A, to our knowledge, has rarely been correlated with USH type 2, our findings therefore reveal distinguished clinical phenotypes associated with MYO7A. We also conclude that targeted NGS is an effective approach for genetic diagnosis for USH, which can further provide better understanding of genotype-phenotype relationship of the disease.
Gungunes, Askin; Sahin, Mustafa; Demirci, Taner; Ucan, Bekir; Cakir, Evrim; Arslan, Muyesser Sayki; Unsal, Ilknur Ozturk; Karbek, Basak; Calıskan, Mustafa; Ozbek, Mustafa; Cakal, Erman; Delibasi, Tuncay
Cushing's syndrome may be more frequent in some specific patient groups such as type 2 diabetes and obesity. The aim of this study was to investigate the prevalence of Cushing's syndrome in outpatients with type 2 diabetes with poor glycemic control despite at least 3-months insulin therapy. Outpatients with type 2 diabetes whose glycemic control is poor (Hb Alc value >7 %) despite receiving at least 3-months long insulin treatment (insulin alone or insulin with oral antidiabetics) were included. Patients with classic features of Cushing's syndrome were excluded. Overnight 1 mg dexamethasone suppression test (DST) was performed as a screening test. A total of 277 patients with type 2 diabetes whose glycemic control is poor (Hb Alc value >7 %) despite insulin therapy were included. Two of the 277 patients with type 2 diabetes were diagnosed with Cushing's syndrome (0.72 %). Hypertension was statistically more frequent in the patients with cortisol levels ≥1.8 μg/dL than the patients with cortisol levels Cushing's syndrome among patients with type 2 diabetes with poor glycemic control despite insulin therapy is much higher than in the general population. The patients with type 2 diabetes with poor glycemic control despite at least three months of insulin therapy should be additionally tested for Cushing's syndrome if they have high dose insülin requirements.
Full Text Available The article presents the results of researches of peculiarities of burnout syndrome formation in healthcare workers with different types of work motivation. It is discovered that the syndrome is formed for each motivational type as mechanism of psychological protection against the action of certain stressful factors, namely: for instrumental type – an excessive concentration on obtaining material rewards; for professional type – an excessive control of emotions in substantial professional communications and high psycho-emotional overload; for patriotic type – high level of dependence on social approval, a high level of communicative activity, a high level of psycho-emotional overload, for economical type – distrust, for lumpenized – any labor. Prevention of burnout syndrome in healthcare workers has to be realized taking into account peculiarities of psycho-traumatic factors depending on the type of work motivation.
Rabah M. Shawky
Jun 24, 2014 ... associated with Joubert Syndrome and related disorders ... types of the JSRD spectrum have been recently defined: (1) .... family history of a similar condition. ....  Holroyd S, Reiss A, Bryan N. Autistic features in Joubert.
Lhuaire, Martin; Jestin, Agnès; Boulagnon, Camille; Loock, Mélanie; Doco-Fenzy, Martine; Gaillard, Dominique; Diebold, Marie-Danièle; Avisse, Claude; Labrousse, Marc
Sirenomelia or "mermaid syndrome" is a rare congenital anomaly known since antiquity. This congenital anomaly is defined as a polymalformative syndrome that associates major muscle and skeleton abnormalities (unique lower limbs) with visceral abnormalities (unilateral or bilateral renal agenesis, anomalies of the abdominal vascularisation). This phenotype, typical of sirenomelia syndrome, may be more or less severe. The pathogenic mechanisms of this syndrome are still debated and its etiology remains unknown. We report here a new type of sirenomelia that we observed in a fetus belonging to the collection of the Department of Anatomy of Reims, which led us to perform a comprehensive review of the literature on the subject: this type has never been reported and cannot be classified according to the Stocker and Heifetz classification. Moreover, this case also presents a VACTERL association with Thomas syndrome. Copyright © 2013 Wiley Periodicals, Inc.
Colombo, L.; Sala, B.; Montesano, G.; Pierrottet, C.; De Cillà, S.; Maltese, P.; Bertelli, M.; Rossetti, L.
To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), axial length (AL), automated visual field (VF), and EDI OCT. Both retinal and choroidal measures were measured. Stati...
Valentin, Mev; Therkildsen, Christina; Veerla, Srinivas
Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.......Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects....
Stutz, B; Ahola, A J; Harjutsalo, V; Forsblom, C; Groop, P-H
In the general population, habitual coffee consumption is inversely associated with the metabolic syndrome, a syndrome that is rather common also in patients with type 1 diabetes. However, whether coffee intake is beneficially related to the metabolic syndrome also in type 1 diabetes, is not known. We, therefore, studied the potential association between coffee consumption and the metabolic syndrome in a large population of individuals with type 1 diabetes. Furthermore, we investigated whether coffee consumption is associated with insulin resistance (estimated glucose disposal rate, eGDR), kidney function (estimated glomerular filtration rate, eGFR), and low-grade chronic inflammation (high-sensitivity C-reactive protein, hsCRP). Data from 1040 participants in the Finnish Diabetic Nephropathy Study were included in these cross-sectional analyses. Metabolic syndrome was assumed if at least 3 of the following cardiovascular risk factors were present: central obesity, high blood pressure, low HDL-cholesterol concentration, high triglyceride concentration, and hyperglycaemia. Subjects were categorized based on self-reported daily coffee intake: non-consumers (metabolic syndrome. Moreover, any level of coffee consumption was associated with increased risk of the blood pressure-component. An increasing trend was observed in the eGFR with increasing coffee consumption. In type 1 diabetes, high coffee intake is associated with the metabolic syndrome, and especially its blood pressure-component. Copyright © 2018. Published by Elsevier B.V.
Chun, Stephen G; Pedro, Patrick; Yu, Mihae; Takanishi, Danny M
Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency. PMID:21966332
Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.
Our patient had normal psychomotor development. His father was similarly affected suggesting autosomal dominant inheritance. The patient had red brown hair, lymphedema of lower limbs and kidney stones which were not reported before with this syndrome. Most probably these additional features are associations with ...
Majority had three coronary artery disease (CAD) risk factors: obesity 86%, elevated LDL 73% and hypertension 60%. Therapy in use was OHA 43%, insulin 42%, insulin and OHA 1%; prophylactic aspirin 14.7% and statins 8.4%. Thirty four (35.8%) were classified as acute coronary syndrome (ACS); 29 ( 30.5%) acute ...
Miner, I. D.
Describes the experiences of individuals with Usher Syndrome, discusses the lack of appropriate services and the failure of professionals to provide sufficient information on the condition, and stresses the importance of access to information and the acquisition of new skills before the visual impairment becomes severe. (Author/CR)
Corey, Linda A; Pellock, John M; Kjeldsen, Marianne J
not appear to play an important role in determining risk for frontal, occipital or temporal lobe epilepsy. These results suggest that, while genetic factors contribute to risk for major syndrome types, determined when possible, their contribution to risk for localization-related syndrome sub......Although there is strong evidence that genetic factors contribute to risk for epilepsy, their role in the determination of syndrome type is less clear. This study was undertaken to address this question. Information related to epilepsy was obtained from twins included in 455 monozygotic and 868...... dizygotic pairs ascertained from population-based twin registries in Denmark, Norway and the United States. Syndrome type was determined based on medical record information and detailed clinical interviews and classified using the International Classification Systems for the Epilepsies and Epileptic...
Full Text Available Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47, XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.
Chen, Kaitian; Zhan, Yuan; Wu, Xuan; Zong, Ling; Jiang, Hongyan
Waardenburg syndrome mutations are most often recurrent or de novo. The rate of familial recurrence is low and families with several affected children are extremely rare. In this study, we aimed to clarify the underlying hereditary cause of Waardenburg syndrome type I in two siblings in a Chinese family, with a mother affected by prelingual mild hearing loss and a father who was negative for clinical symptoms of Waardenburg syndrome and had a normal hearing threshold. Complete characteristic features of the family members were recorded and genetic sequencing and parent-child relationship analyses were performed. The two probands were found to share double mutations in the PAX3/GJB2 genes that caused concurrent hearing loss in Waardenburg syndrome type I. Their mother carried the GJB2 c.109G > A homozygous mutation; however, neither the novel PAX3 c.592delG mutation, nor the Waardenburg syndrome phenotype, was observed in either parent. These previously unreported digenic mutations in PAX3/GJB2 resulted in deafness associated with Waardenburg syndrome type I in this family. To our knowledge, this is the first report describing germinal mosaicism in Waardenburg syndrome. This concept is important because it complicates genetic counseling of this family regarding the risk of recurrence of the mutations in subsequent pregnancies. Copyright © 2017 Elsevier B.V. All rights reserved.
Ahola, Aila J; Thorn, Lena M; Saraheimo, Markku; Forsblom, Carol; Groop, Per-Henrik
Both depression and the metabolic syndrome are frequently found among patients with type 1 diabetes, but their potential association has not yet been investigated. In this paper the relationship between depression and the metabolic syndrome among patients with type 1 diabetes was evaluated. A total of 1226 patients participating in the Finnish Diabetic Nephropathy Study between 2003 and 2009 were included. Depression was defined as use of antidepressive medication or Beck Depression Inventory (BDI) score ≥16. The metabolic syndrome was defined using the criteria established by the International Diabetes Federation Task Force on Epidemiology and Prevention (IDF); National Heart, Lung, and Blood Institute (NHLBI); American Heart Association (AHA); World Heart Federation (WHF); International Atherosclerosis Society (IAS); and International Association for the Study of Obesity (IASO). The metabolic syndrome was more frequently observed among depressed patients (57% versus 46%, P = 0.008). Of the individual components of the metabolic syndrome, waist, triglyceride, and HDL components were more frequently fulfilled among patients with depression. The BDI score increased with the number of components of the metabolic syndrome present. The BDI score was independently associated with the waist component (odds ratio 1.03, 95% confidence interval 1.01-1.05) when adjusted for gender, age, socio-economic status, smoking, nephropathy, and HbA(1c). The metabolic syndrome is frequently found among depressed patients with type 1 diabetes. Whether this association influences the development of diabetic complications is not known.
Beckers, A B; Keszthelyi, D; Fikree, A; Vork, L; Masclee, A; Farmer, A D; Aziz, Q
Joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome hypermobility type (EDS-HT) is the most common hereditary non-inflammatory disorder of connective tissue, characterized by a wide range of symptoms, mainly joint hyperextensibility and musculoskeletal symptoms. A majority of patients also experiences gastrointestinal (GI) symptoms. Furthermore, JHS/EDS-HT has specifically been shown to be highly prevalent in patients with functional GI disorders, such as functional dyspepsia and irritable bowel syndrome. The aim of this review was to examine the nature of GI symptoms and their underlying pathophysiology in JHS/EDS-HT. In addition, we consider the clinical implications of the diagnosis and treatment of JHS/EDS-HT for practicing clinicians in gastroenterology. Observations summarized in this review may furthermore represent the first step toward the identification of a new pathophysiological basis for a substantial subgroup of patients with functional GI disorders. © 2017 John Wiley & Sons Ltd.
Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M
Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.
Full Text Available Wolfram syndrome is a rare autosomal recessive disorder characterized by a constellation of disorders also known as diabetes insipidus, diabetes mellitus (DM, optic atrophy, and deafness. Patients present with DM and optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, and renal outflow tract anomalies and other neurological manifestations later in life. We report a case of a 14-year-old boy who was diagnosed with insulin-dependent DM and subsequently discovered to have optic atrophy, sensorineural hearing loss, and cardiovascular defect with a positive family history. Such cases need to be evaluated thoroughly with respect to Wolfram syndrome and its associated anomalies.
Salerno, Francesco; Navickis, Roberta J; Wilkes, Mahlon M
Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes. Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose. Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period. This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of
Full Text Available Objective: To investigate the phenotype-genotype correlation in different genetic kinds of Bartter syndrome type 3 in children.Methods: Clinical and genetic data of 2 patients with different mutations in Bartter syndrome type 3 was analyzed while the prognosis was compared after a 6-year follow-up or 2-year follow-up, respectively.Results: Bartter syndrome is a kind of autosomal recessive inherited renal disorder. The manifestation and prognosis of Bartter syndrome change with mutation types, and severe mutation were often accompanied with unfavorable prognosis. Comprehensive therapy with ibuprofen, antisterone, captopril, and potassium have remarkable effect, while ibuprofen may improve growth retardation partly.Conclusion: Bartter syndrome should be considered when children have unreasonable continuous electrolyte disturbance, metabolic alkalosis and growth retardation.As a genetic disease, its clinical features depend on the mutation type. It can be ameliorated by electrolyte supplementation, prostaglandin synthetase inhibitors, angiotensin-converting enzyme inhibitors and potassium-sparing diuretic. Considering the following electrolyte disturbances, infections, growth retardation, kidney failure and even death, Bartter syndrome need lifelong treatment, early diagnosis and treatment is the most important.
Oshima, A.; Jaijo, T.; Aller, E.; Millan, J.M.; Carney, C.; Usami, S.; Moller, C.; Kimberling, W.J.
Mutations in the human gene encoding cadherin 23 (CDH23) cause Usher syndrome type 1D (USH1D) and nonsyndromic hearing loss. Individuals with Usher syndrome type I have profound congenital deafness, vestibular areflexia and usually begin to exhibit signs of RP in early adolescence. In the present study, we carried out the mutation analysis in all 69 exons of the CDH23 gene in 56 Usher type 1 probands already screened for mutations in MYO7A. A total of 18 of 56 subjects (32.1%) were observed to have one or two CDH23 variants that are presumed to be pathologic. Twenty one different pathologic genome variants were observed of which 15 were novel. Out of a total of 112 alleles, 31 (27.7%) were considered pathologic. Based on our results it is estimated that about 20% of patients with Usher syndrome type I have CDH23 mutations. PMID:18429043
Gera, D. N.; Ghuge, P. P.; Gandhi, S.; Vanikar, A. V.; Shrimali, J. D.; Kute, V. B.; Trivedi, H. L.
Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated...
The present thesis belongs to the research area disability research and deal with specific aspects of cognition in individuals with Usher syndrome type 1 and 2. The subject has been investigated and is discussed within an interdisciplinary framework, though the theories applied and described are derived from the area of cognitive psychology. Usher syndrome is a rare genetic condition causing a combination of visual and hearing impairment: deafblindness. There is a congenital hearing loss that...
Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias
To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PC...
Damen, G.W.J.A.; Pennings, R.J.E.; Snik, A.F.M.; Mylanus, E.A.M.
OBJECTIVES: The objectives of this descriptive, retrospective study were to evaluate quality of life, hearing, and vision in patients with Usher syndrome type I with and without cochlear implant. METHODS: Quality of life (QoL) of 14 patients with Usher type I (USH1) with a cochlear implant (CI)
DeAngelis, M M; McGee, T L; Keats, B J; Slim, R; Berson, E L; Dryja, T P
To search for patients with Usher syndrome type IC among those with Usher syndrome type I who reside in New England. Genotype analysis of microsatellite markers closely linked to the USH1C locus was done using the polymerase chain reaction. We compared the haplotype of our patients who were homozygous in the USH1C region with the haplotypes found in previously reported USH1C Acadian families who reside in southwestern Louisiana and from a single family residing in Lebanon. Of 46 unrelated cases of Usher syndrome type I residing in New England, two were homozygous at genetic markers in the USH1C region. Of these, one carried the Acadian USH1C haplotype and had Acadian ancestors (that is, from Nova Scotia) who did not participate in the 1755 migration of Acadians to Louisiana. The second family had a haplotype that proved to be the same as that of a family with USH1C residing in Lebanon. Each of the two families had haplotypes distinct from the other. This is the first report that some patients residing in New England have Usher syndrome type IC. Patients with Usher syndrome type IC can have the Acadian haplotype or the Lebanese haplotype compatible with the idea that at least two independently arising pathogenic mutations have occurred in the yet-to-be identified USH1C gene.
Scheper, Mark C; de Vries, Janneke E; Verbunt, Jeanine; Engelbert, Raoul HH
Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in ≥4 joints over a period ≥3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition, GJH
Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Albertini, Giorgio; Camerota, Filippo
Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It has recently been shown that muscle weakness occurs frequently in EDS, and that fatigue is a common and clinically important symptom. The…
Scheper, Mark C.; de Vries, Janneke E.; Verbunt, Jeanine; Engelbert, Raoul H. H.
Generalized joint hypermobility (GJH) is highly prevalent among patients diagnosed with chronic pain. When GJH is accompanied by pain in >= 4 joints over a period >= 3 months in the absence of other conditions that cause chronic pain, the hypermobility syndrome (HMS) may be diagnosed. In addition,
Logadottir, Yr; Delbro, Dick; Fall, Magnus; Gjertsson, Inger; Jirholt, Pernilla; Lindholm, Catharina; Peeker, Ralph
Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls. Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count. IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C. Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Hakim, Alan; De Wandele, Inge; O'Callaghan, Chris; Pocinki, Alan; Rowe, Peter
Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Uribe-Wiechers, Ana Cecilia; Janka-Zires, Marcela; Almeda-Valdés, Paloma; López-Gutiérrez, Joel; Gómez-Pérez, Francisco J
The development of metabolic syndrome has been described in patients with type 1 diabetes mellitus as the disease progresses over time. The purpose of this study is to assess the relationship between metabolic syndrome, albuminuria, and glomerular filtration rate, as well as to determine the prevalence of metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus. We conducted a cross-sectional study that included patients with type 1 diabetes mellitus who were diagnosed over 10 years ago and who are seen at the Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was determined by using the National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. A total of 81 individuals were studied. The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02). Glomerular filtration rate was lower in patients with metabolic syndrome (95.3 ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After classifying the population according to the number of metabolic syndrome criteria, a progressive increase in albuminuria and a progressive decrease in glomerular filtration rate were found with each additional metabolic syndrome criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and treatment with angiotensin receptor blockers or angiotensin converting enzyme inhibitors, we found that age, time from diagnosis, triglycerides, and HDL-cholesterol were independent factors associated with glomerular filtration rate (R2 = 0.286; p diabetes mellitus. Metabolic syndrome was present in 18.5% of this group of Mexican individuals with type 1 diabetes
Full Text Available Michael J Davies,1 Katherine W Merton,1 Ujjwala Vijapurkar,2 Dainius A Balis,2 Mehul Desai2 1Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 2Janssen Research & Development, LLC, Raritan, NJ, USA Objective: Metabolic syndrome refers to a collection of risk factors associated with the development of cardiovascular disease and type 2 diabetes mellitus (T2DM. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight and blood pressure (BP in a broad range of patients with T2DM. This post hoc analysis assessed the effects of canagliflozin on the components of metabolic syndrome in patients with T2DM and metabolic syndrome.Methods: This analysis was based on data from 2 head-to-head studies of canagliflozin in patients with T2DM on background metformin versus glimepiride (study 1 and background metformin plus sulfonylurea versus sitagliptin 100 mg (study 2. Changes from baseline in glycemic efficacy, anthropometric measures, BP, and lipids were evaluated with canagliflozin versus glimepiride and sitagliptin at week 52 in patients who met ≥2 of the criteria for metabolic syndrome (in addition to T2DM: triglycerides ≥1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C <1.0 mmol/L (men or <1.3 mmol/L (women; waist circumference ≥102 cm (non-Asian men, ≥88 cm (non-Asian women, >90 cm (Asian men, or >80 cm (Asian women; diagnosis of hypertension or meeting BP-related criteria (systolic BP ≥130 mmHg or diastolic BP ≥85 mmHg. Safety was assessed based on adverse event reports.Results: In study 1, canagliflozin 100 and 300 mg provided similar and greater HbA1c reductions versus glimepiride, respectively. In study 2, canagliflozin 300 mg provided greater HbA1c lowering versus sitagliptin 100 mg. Canagliflozin also reduced fasting plasma glucose, body weight, body mass index, waist circumference, BP, and triglycerides, and increased HDL-C and low-density lipoprotein cholesterol versus
Zhou, Qi; Lenger, Chaeli; Smith, Richard; Kimberling, William J; Ye, Ming; Lehmann, Ordan; MacDonald, Ian
To identify the genetic defect in a Hutterite population from northern Alberta with Usher syndrome type I. Complete ophthalmic examinations were conducted on two boys and two girls from two related Hutterite families diagnosed with Usher syndrome type I. DNA from patients and their parents was first evaluated for a mutation in exon 10 of the protocadherin-related 15 (PCDH15) gene (c.1471delG), previously reported in southern Alberta Hutterite patients with Usher syndrome (USH1F). Single nucleotide polymorphic linkage analysis was then used to confirm another locus, and DNA was analyzed with the Usher Chip v4.0 platform. Severe hearing impairment, unintelligible speech, and retinitis pigmentosa with varying degrees of visual acuity and visual field loss established a clinical diagnosis of Usher syndrome type I. The patients did not carry the exon 10 mutation in the PCDH15 gene; however, with microarray analysis, a previously reported mutation (c.52C>T; p.Q18X) in the myosin VIIA (MYO7A) gene was found in the homozygous state in the affected siblings. The finding of a MYO7A mutation in two related Hutterite families from northern Alberta provides evidence of genetic heterogeneity in Hutterites affected by Usher syndrome type I.
Full Text Available Objectives The aim of this study was to investigate the prevalence of metabolic syndrome, in children with type one diabetes mellitus (T1DM for the first time in a population in the Middle East, and assess the influence of type of insulin therapy, daily dosage of insulin, family history of type 2 diabetes, gender and level of HbA1c on the prevalence of metabolic syndrome. Methods This cross-sectional study was conducted on children with T1DM aged 2 years during years 2013 to 2014. Waist circumference, blood pressure, height and weight of children with diabetes, for calculation of body mass index (BMI, were measured by one physician. Fasting blood glucose and lipids were also measured. According to the age-modified standards of the ATPIII, metabolic syndrome was defined. All data were analyzed using the SPSS 18 software. Results In this study, 87 children with diabetes (48 females and 39 males aged 12.38 ± 4.2 were enrolled. Overall, 40.9% of our patients had hypertension, 55.2% had hypertriglyceridemia, 36.8% had low high-density lipoprotein (HDL and 6.9% of patients had abdominal obesity. Furthermore, 29.9% of these children had metabolic syndrome, which did not have a significant association with the type of insulin regimen (P = 0.97, nor the daily dosage of insulin (P = 0.234, however the serum concentration of HbA1c had a significant correlation with metabolic syndrome (P = 0.027. Conclusions This study provides evidence indicating high prevalence of metabolic syndrome in children with T1DM in southern Iran. Preventive programs aimed towards decreasing the risk factors of metabolic syndrome and interpretation of a healthier diet and physical activity for children with T1DM should be considered in our country.
Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir
Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia.
Full Text Available Turcot syndrome is an autosomal recessive disorder clinically characterized by the occurrence of primary tumors of the central nervous system and adenomatous colonic polyps during the first or second decades of life, with a spectrum of clinical features such as “café-au-lait” spots, axillary freckling, and hyperpigmented spots. Currently its prevalence globally and in Colombia remains unknown. We present the case of a 20-year-old male with a clinical presentation of both glioblastoma multiforme and multiple adenomatous colonic polyps. The molecular genetics study revealed a mutation in KrasAsp12 gene and altered expression of HMSH2 and HMSH6 proteins encoded by the DNA mismatch repair genes in two of the colonic polyps. Even though this clinical presentation may suggest a shorter survival rate, this patient is still alive after seven months of treatment. A literature review complements this report.
Full Text Available The diagnosis of child maltreatment leading to head injury is challenging. Here, we present the case of a 3-month-old female infant who presented with focal seizures that lasted for several minutes. After admission, she began to show intermittent clusters of head nods, irritable crying, arching, writhing, stiffening, and jerking of both arms. These results and electroencephalography findings were attributed as the diagnosis of infantile spasms (IS. Brain computed tomography and magnetic resonance imaging (MRI revealed the presence of chronic subdural hematoma mixed with acute ischemic injuries. Examination of the eye fundus confirmed the presence of retinal hemorrhage. Therefore, all evidence pointed to a diagnosis of shaken baby syndrome (SBS. Based on this case, we suggest that physicians should consider a diagnosis of SBS for children with new-onset IS and that should be evaluated, diagnosed, and treated as promptly as possible.
Wang, Hong-Han; Feng, Yong; Li, Hai-Bo; Wu, Hong; Mei, Ling-Yun; Wang, Xing-Wei; Jiang, Lu; He, Chu-Feng
Bartter syndrome type IV, characterized by salt-losing nephropathies and sensorineural deafness, is caused by mutations of BSND or simultaneous mutations of both CLCNKA and CLCNKB. GJB2 is the primary causative gene for non-syndromic sensorineural deafness and associated with several syndromic sensorineural deafness. Owing to the rarity of Bartter syndrome, only a few mutations have been reported in the abovementioned causative genes. To investigate the underlying mutations in a Chinese patient with Bartter syndrome type IV, genetic analysis of BSND, CLCNKA, CLCNKB and GJB2 were performed by polymerase chain reaction and direct sequencing. Finally, double homozygous mutations c.22C > T (p.Arg8Trp) and c.127G > A (Val43Ile) were detected in exon 1 of BSND. Intriguingly, compound heterozygous mutations c.235delC (p.Leu79CysfsX3) and c.109G > A (p.Val37Ile) were also revealed in exon 2 of GJB2 in the same patient. No pathogenic mutations were found in CLCNKA and CLCNKB. Our results indicated that the homozygous mutation c.22C > T was the key genetic reason for the proband, and a digenic effect of BSND and GJB2 might contributed to sensorineural deafness. To our knowledge, it was the first report showing that the GJB2 gene mutations were detected in Bartter syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Sahu, Sabin; Singh, Sanjay Kumar
Usher syndrome, also known as retinitis pigmentosa-dysacusis syndrome, is an extremely rare genetic disorder, characterized by retinitis pigmentosa (RP) and congenital sensorineural hearing loss. It has been estimated to account for 3-6% of the congenitally deaf population, upto 8-33% of individuals with RP and half of all cases with combined deafness and blindness (Vernon M,1969; Boughman JA et al,1983). The prevalence of Usher syndrome have been reported to range from 3.5 to 6.2 per 100,000 in different populations (Vernon M,1969; Boughman JA et al,1983; Yan D et al, 2010). We report a case of Usher syndrome type I in an adult Nepalese male with typical congenital profound hearing loss, and night blindness secondary to retinitis pigmentosa. © NEPjOPH.
Pieke-Dahl, S; Moller, C; Kelley, P; Astuto, L; Cremers, C; Gorin, M; Kimberling, W
Usher syndrome is a group of autosomal recessive disorders that includes retinitis pigmentosa (RP) with hearing loss. Usher syndrome type II is defined as moderate to severe hearing loss with RP. The USH2A gene at 1q41 has been isolated and characterised. In 1993, a large Usher II family affected with a mild form of RP was found to be unlinked to 1q41 markers. Subsequent linkage studies of families in our Usher series identified several type II families unlinked to USH2A and USH3 on 3q25. Aft...
Moran, Lisa J; Misso, Marie L; Wild, Robert A; Norman, Robert J
BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women associated with impaired glucose tolerance (IGT), type 2 diabetes mellitus (DM2) and the metabolic syndrome. METHODS A literature search was conducted (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) identifying studies reporting prevalence or incidence of IGT, DM2 or metabolic syndrome in women with and without PCOS. Data were presented as odds ratio (OR) [95% confidence interval (CI)] with fixed- and random-effects meta-analysis by Mantel-Haenszel methods. Quality testing was based on Newcastle-Ottawa Scaling and The Cochrane Collaboration's risk of bias assessment tool. Literature searching, data abstraction and quality appraisal were performed by two investigators. RESULTS A total of 2192 studies were reviewed and 35 were selected for final analysis. Women with PCOS had increased prevalence of IGT (OR 2.48, 95% CI 1.63, 3.77; BMI-matched studies OR 2.54, 95% CI 1.44, 4.47), DM2 (OR 4.43, 95% CI 4.06, 4.82; BMI-matched studies OR 4.00, 95% CI 1.97, 8.10) and metabolic syndrome (OR 2.88, 95% CI 2.40, 3.45; BMI-matched studies OR 2.20, 95% CI 1.36, 3.56). One study assessed IGT/DM2 incidence and reported no significant differences in DM2 incidence (OR 2.07, 95% CI 0.68, 6.30). One study assessed conversion from normal glucose tolerance to IGT/DM2 (OR 2.4, 95% CI 0.7, 8.0). No studies reported metabolic syndrome incidence. CONCLUSIONS Women with PCOS had an elevated prevalence of IGT, DM2 and metabolic syndrome in both BMI and non-BMI-matched studies. Few studies have determined IGT/DM2 or metabolic syndrome incidence in women with and without PCOS and further research is required.
Full Text Available Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1% who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%, which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.
Yoshimura, Hidekane; Iwasaki, Satoshi; Nishio, Shin-Ya; Kumakawa, Kozo; Tono, Tetsuya; Kobayashi, Yumiko; Sato, Hiroaki; Nagai, Kyoko; Ishikawa, Kotaro; Ikezono, Tetsuo; Naito, Yasushi; Fukushima, Kunihiro; Oshikawa, Chie; Kimitsuki, Takashi; Nakanishi, Hiroshi; Usami, Shin-Ichi
Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.
Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J
Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Andrini, Olga; Keck, Mathilde; Briones, Rodolfo; Lourdel, Stéphane; Vargas-Poussou, Rosa; Teulon, Jacques
The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the genetically based nomenclature. All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism, but Bartter syndrome type 3 has the most heterogeneous presentation, extending from severe to very mild. A relatively large number of CLCNKB mutations have been reported, including gene deletions and nonsense or missense mutations. However, only 20 CLCNKB mutations have been functionally analyzed, due to technical difficulties regarding ClC-Kb functional expression in heterologous systems. This review provides an overview of recent progress in the functional consequences of CLCNKB mutations on ClC-Kb chloride channel activity. It has been observed that 1) all ClC-Kb mutants have an impaired expression at the membrane; and 2) a minority of the mutants combines reduced membrane expression with altered pH-dependent channel gating. Although further investigation is needed to fully characterize disease pathogenesis, Bartter syndrome type 3 probably belongs to the large family of conformational diseases, in which the mutations destabilize channel structure, inducing ClC-Kb retention in the endoplasmic reticulum and accelerated channel degradation. Copyright © 2015 the American Physiological Society.
Full Text Available Ehlers-Danlos Syndrome Hypermobility Type/Joint Hypermobility Syndrome (JHS/EDS-HT is an hereditary disorder of the connective tissue mainly manifesting with generalized joint hypermobility and skin hyperextensibility with an involvement of the connective tissue matrix proteins. Collagen alterations may influence the quality of movement in these patients but also movement has a role for the collagen quality: motion has a prevention role in the formation of contractures and adhesions. A poor sense of proprioception correlated with the collagenous connective tissues alterations could explain why people with JHS/EDS-HT become injured, having a lack of sensation of the joint at the end of the range. Rehabilitation approach may consider all these aspects.
Lu, Yanqin; Wang, Yanzhou; Rauch, Frank; Li, Hu; Zhang, Yao; Zhai, Naixiang; Zhang, Jian; Ren, Xiuzhi; Han, Jinxiang
Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are rare genetic disorders that are typically inherited in an autosomal dominant manner. Few cases of OI/EDS overlap syndrome have been documented. Described here is a 30-year-old Chinese male with OI type III and EDS. Sequencing of genomic DNA revealed a heterozygous COL1A1 mutation (c.671G>A, p.Gly224Asp) that affected the N-anchor domain of the alpha 1 chain of collagen type I. Ultrastructural analysis of a skin biopsy specimen revealed thin collagen fibers with irregular alignment of collagen fibers. These findings have expanded the genotypic spectrum of the OI/EDS overlap syndrome.
Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Kashyap, Rahul; Kashani, Kianoush; Jentzer, Jacob C
To evaluate the clinical features and outcomes of acute cardiorenal syndrome type-5 in patients with severe sepsis and septic shock. Historical cohort study of all adult patients with severe sepsis and septic shock admitted to the intensive care units (ICU) at Mayo Clinic Rochester from January 1, 2007 through December 31, 2014. Patients with prior renal or cardiac dysfunction were excluded. Patients were divided into groups with and without cardiorenal syndrome type-5. Acute Kidney Injury (AKI) was defined by both serum creatinine and urine output criteria of the AKI Network and the cardiac injury was determined by troponin-T levels. Outcomes included in-hospital mortality, ICU and hospital length of stay, and one-year survival. Of 602 patients meeting the study inclusion criteria, 430 (71.4%) met criteria for acute cardiorenal syndrome type-5. Patients with cardiorenal syndrome type-5 had higher severity of illness, greater vasopressor and mechanical ventilation use. Cardiorenal syndrome type-5 was associated higher unadjusted in-hospital mortality, ICU and hospital lengths of stay, and lower one-year survival. When adjusted for age, gender, severity of illness and mechanical ventilation, cardiorenal syndrome type-5 was independently associated with 1.7-times greater odds of in-hospital mortality (p = .03), but did not predict one-year survival (p = .06) compared to patients without cardiorenal syndrome. In sepsis, acute cardiorenal syndrome type-5 is associated with worse in-hospital mortality compared to patients without cardiorenal syndrome.
Johannessen, Elise Christine; Reiten, Helle Sundnes; Løvaas, Helene
Purpose To investigate shoulder function, pain and Health-Related Quality of life (HRQoL) among adults with joint hypermobility syndrome/Ehlers-Danlos syndrome-hypermobility type (JHS/EDS-HT), compared with the general population (controls). Method In a cross-sectional study using postal survey...
Jabbari Azad, Farahzad; Ardalan, Maryam; H.Rafati, Ali
Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl...
Wessels, M.W.; Hollander, N.S.; Cohen-Overbeek, T.E.; Lesnik Oberstein, M.S.; Nash, R.M.; Wladimiroff, J.W.; Niermeijer, M.F.; Willems, P.J.
The group of acrofacial dysostosis (AFD) syndromes is very heterogeneous and contains many different entities. In 1990, Rodriguez et al. [1990: Am J Med Genet 35:484-489] described a new type of AFD characterized by severe mandibular hypoplasia, phocomelia and oligodactyly of the upper limbs,
Alizadeh Dehnavi, R.; Beishuizen, E.D.; Ree, M.A. van de; Le Cessie, S.; Huisman, M.V.; Kluft, C.; Princen, H.M.G.; Tamsma, J.T.
Background: The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2. Methods: Vascular phenotype was determined using the following
Tan, E.C.T.H.; Janssen, A.J.W.M.; Roestenberg, P.M.H.; Heuvel, L.P.W.J. van den; Goris, R.J.A.; Rodenburg, R.J.T.
Reactive oxygen species (ROS) are known to be involved in the pathophysiology of complex regional pain syndrome type I (CRPS I). Since the mitochondrial respiratory chain is a major source of ROS, we hypothesized that mitochondria play a role in the pathophysiology of CRPS I. The hypothesis was
Tan, E.C.T.H.; Tacken, M.C.; Groenewoud, J.M.M.; Goor, H. van; Frolke, J.P.M.
INTRODUCTION: Complex Regional Pain Syndrome Type I (CRPS I) is a continuation of symptoms and signs due to a pathological exaggerated reaction in an extremity of the human body after an injury or operation. Although the clinical picture of CRPS I in the majority of patients is well known, the
Frank J. P. M. Huygen
Full Text Available Background: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1 is still a matter of debate. Peripheral afferent, efferent and central mechanisms are supposed. Based on clinical signs and symptoms (e.g. oedema, local temperature changes and chronic pain local inflammation is suspected.
Bodde, Marlies I.; Dijkstra, Pieter U.; Schrier, Michiel; van den Dungen, Johannes; den Dunnen, Wilfred E.; Geertzen, Joannes
Background: Literature on complex regional pain syndrome type I (CRPS-I) discussing the decision to amputate or not, the level of amputation, or the timing of the amputation is scarce: We evaluated informed decision-making regarding amputation for CRPS-I. Methods: We describe our findings in a
Svačina, Š.; Matoulek, M.; Svobodová, S.; Visokai, V.; Lipská, L.; Plavcová, Marie; Zvárová, Jana
Roč. 29, 4 suppl. (2003), s. 359 ISSN 0338-1684. [International Diabetes Federation Congress /18./. 24.08.2003-29.08.2003, Paris] R&D Projects: GA MZd NB6635; GA MŠk LN00B107 Keywords : diabetes type 2 * metabolic syndrome * colorectal cancer Subject RIV: BB - Applied Statistics, Operational Research
Gasparini, P; De Fazio, A; Croce, A I; Stanziale, P; Zelante, L
We report an Italian family affected by Usher type III syndrome. Linkage study, performed using markers corresponding to the Usher loci already mapped, clearly showed linkage with markers on chromosome 3q24-25. Our data further support the presence of an Usher III locus on chromosome 3, as recently reported in a Finnish population.
Gasparini, P; De Fazio, A; Croce, A I; Stanziale, P; Zelante, L
We report an Italian family affected by Usher type III syndrome. Linkage study, performed using markers corresponding to the Usher loci already mapped, clearly showed linkage with markers on chromosome 3q24-25. Our data further support the presence of an Usher III locus on chromosome 3, as recently reported in a Finnish population.
Pennings, R.J.E.; Brinke, H. te; Weston, M.D.; Claassen, A.M.W.; Orten, D.J.; Weekamp, H.; Aarem, A. van; Huygen, P.L.M.; Deutman, A.F.; Hoefsloot, L.H.; Cremers, F.P.M.; Cremers, C.W.R.J.; Kimberling, W.J.; Kremer, J.M.J.
Usher syndrome type II (USH2) is characterised by moderate to severe high-frequency hearing impairment, progressive visual loss due to retinitis pigmentosa and intact vestibular responses. Three loci are known for USH2, however, only the gene for USH2a (USH2A) has been identified. Mutation analysis
Gieteling, Esther W.; van Rijn, Monique A.; de Jong, Bauke M.; Hoogduin, Johannes M.; Renken, Remco; van Hilten, Jacobus J.; Leenders, Klaus L.
The pathogenesis of dystonia in Complex Regional Pain Syndrome type 1 (CRPS-1) is unclear. In primary dystonia, functional magnetic resonance imaging (fMRI) has revealed changes in cerebral networks during execution of movement. The aim of this study was to determine cerebral network function in
Hagspiel, Klaus D.; Bonatti, Hugo; Sabri, Saher; Arslan, Bulent; Harthun, Nancy L.
Ehlers-Danlos syndrome type IV is a life-threatening genetic connective tissue disorder. We report a 24-year-old woman with EDS-IV who presented with metachronous bilateral aneurysms/pseudoaneurysms of the posterior tibial arteries 15 months apart. Both were treated successfully with transarterial coil embolization from a distal posterior tibial approach.
Wahlqvist, Moa; Moller, Claes; Moller, Kerstin; Danermark, Berth
Introduction: The objectives of the study reported here were to describe the physical and psychological health of persons with Usher syndrome Type II (USH2) and to explore any differences in terms of gender. Methods: The participants were recruited from the Swedish Usher database. In the first step, 122 persons received the questionnaire by mail,…
Miner, I. D.
Usher syndrome, Type I, requires multiple adaptations throughout the life cycle because each stage of life has tasks and losses associated with deafness and progressive retinitis pigmentosa. This article examines the issues raised at each stage, using clinical vignettes from persons who have this condition and their families. (Author/DB)
Hartel, B.P.; Nierop, J.W.I. van; Huinck, W.J.; Rotteveel, L.J.C.; Mylanus, E.A.M.; Snik, A.F.M.; Kunst, H.P.M.; Pennings, R.J.E.
OBJECTIVES: Usher syndrome type IIa (USH2a) is characterized by congenital moderate to severe hearing impairment and retinitis pigmentosa. Hearing rehabilitation starts in early childhood with the application of hearing aids. In some patients with USH2a, severe progression of hearing impairment
Geertzen, JHB; de Bruijn-Kofman, AT; de Bruijn, HP; van de Wiel, HBM; Dijkstra, PU
Objective: To determine to what extent stressful life events and psychological dysfunction play a role in the pathogenesis of Complex Regional Pain Syndrome type I (CRPS). Design: A comparative study between a CRPS group and a control group. Stressful life events and psychological dysfunction
Bodde, Marlies I.; Schrier, Ernst; Krans, Hilde K.; Geertzen, J.H.B.; Dijkstra, Pieter U.
Purpose: Although controversial, an amputation for longstanding and therapy-resistant Complex Regional Pain Syndrome Type I (CRPS-I) may improve quality of life and pain intensity. Resilience, the way people deal with adversity in a positive way may be related to these positive outcomes. This study
Full Text Available Abstract Background This study was performed to assess the prevalence of dry eye syndrome and diabetic retinopathy (DR in type 2 diabetic patients and their contributing factors. Methods 199 type 2 diabetic patients referred to Yazd Diabetes Research Center were consecutively selected. All Subjects were assessed by questionnaire about other diseases and drugs. Dry eye syndrome was assessed with Tear break up time tests and Schirmer. All the subjects underwent indirect ophthalmoscopy and retinal color photography. DR was graded according to early Treatment Diabetic Retinopathy (ETDRS criteria. Results Of 199 subjects, 108 patients (54.3% suffer from dry eye syndrome. Although dry eye syndrome was more common in older and female patients, this association was not significant. But there was significantly association between dry eye syndrome and duration of diabetes (P = 0.01. Dry eye syndrome was more frequent in diabetic patients with DR (P = 0.02. DR was found in 140 patients (70.35%, which included 34 patients (17.1% with mild non proliferative DR (NPDR, 34 patients (17.1% with moderate NPDR, 22 patients (11.1% with severe NPDR and 25 patients (25.1% with proliferative DR (PDR. There were significant relation between age, sex and duration of diabetes and DR. Conclusion In this study the prevalence of dry eye syndrome was 54.3%. Diabetes and dry eyes appear to have a common association. Further studies need to be undertaken to establish an etiologic relationship. However, examination for dry eye should be an integral part of the assessment of diabetic eye disease.
Full Text Available BACKGROUND Hepatorenal syndrome is a pre-renal like dysfunction that generally onsets in cirrhotic patients presenting ascites. MATERIALS AND METHODS We investigated the improvement of renal function in subjects with hepatorenal syndrome after terlipressin administration and the survival times after this treatment. 30 patients affected by cirrhosis, with diagnosis of type I hepatorenal syndrome were treated with intravenous terlipressin plus albumin (group A or with albumin alone (group B. Liver function, renal function, sodium plasma level and plasma renin activity were monitored. RESULTS Patients of group A showed a significant improvement (p < 0.001 of renal function valued by creatinine rate compared with the results obtained in group B. The probability of survival was higher in the group A (p < 0.0001. CONCLUSIONS Our results seem to confirm that the administration of terlipressin plus albumin improves renal function in patients with cirrhosis and type I hepatorenal syndrome and that a reversal of hepatorenal syndrome is strongly associated with an improved survival.
Puricelli, Elena; Bettinelli, Alberto; Borsa, Nicolò; Sironi, Francesca; Mattiello, Camilla; Tammaro, Fabiana; Tedeschi, Silvana; Bianchetti, Mario G
Little information is available on a long-term follow-up in Bartter syndrome type I and II. Clinical presentation, treatment and long-term follow-up (5.0-21, median 11 years) were evaluated in 15 Italian patients with homozygous (n = 7) or compound heterozygous (n = 8) mutations in the SLC12A1 (n = 10) or KCNJ1 (n = 5) genes. Thirteen new mutations were identified. The 15 children were born pre-term with a normal for gestational age body weight. Medical treatment at the last follow-up control included supplementation with potassium in 13, non-steroidal anti-inflammatory agents in 12 and gastroprotective drugs in five patients. At last follow-up, body weight and height were within normal ranges in the patients. Glomerular filtration rate was Bartter syndrome had a lower renin ratio (P Bartter syndrome. Patients with Bartter syndrome type I and II tend to present a satisfactory prognosis after a median follow-up of more than 10 years. Gallstones might represent a new complication of antenatal Bartter syndrome.
Hope, Lena; Juul-Kristensen, Birgit; Løvaas, Helene; Løvvik, Camilla; Maeland, Silje
To investigate the prevalence and severity of subjective health complaints and describe illness perception in a population of Joint Hypermobility Syndrome or Ehlers-Danlos Syndrome-Hypermobile Type. This study was a postal survey with a questionnaire battery on demographic data, subjective health complaints inventory, and illness perception. A total of 110 individuals diagnosed with Joint Hypermobility Syndrome or Ehlers-Danlos Syndrome-Hypermobile Type from two specialized hospitals in Norway were offered participation. Further, 140 gender- and age-matched healthy controls from statistics Norway representing the general population were sent the questionnaire for reference. Overall response rate was 30.4% (n = 76), with 44.5% (n = 49) in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type and 19.3% (n = 27) in controls. Subjective health complaints were significantly higher in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type - than in the controls (32.06 vs. 11.08; p Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type had low understanding of their illness and symptoms (understanding, mean: 3.93, SD 2.88), and reported to have moderate personal and treatment control over their illness. Adults with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type reported higher frequency and severity of subjective health complaints than the matched controls from the general adult population in Norway. Furthermore, Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type reported low understanding of their illness and associated symptoms, and moderate belief that their illness can be kept under control through self-management or treatment. This may indicate one of the reasons why prognosis for these patients is poor. Implications for rehabilitation Awareness of the complexity of the subjective health complaints and inquiry into illness perception could contribute with valuable information about these
Betterle, Corrado; Garelli, Silvia; Coco, Graziella; Burra, Patrizia
Type 3 autoimmune polyendocrine syndrome (APS-3) is defined by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison's disease; this is a frequent combination. We report the case of a 55 years old female patient with APS-3, with seven clinical or latent autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves' disease, autoimmune leukopenia, latent autoimmune diabetes of the adult (LADA), autoimmune gastritis, ulcerative colitis, Sjögren's and anti-phospholipid syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent (131)I therapy for hyperthyroidism and later started substitutive thyroid therapy with l-thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren's syndrome. In this article we report a complex case of APS-3, characterized by the association of seven different autoimmune diseases, which required a complex therapeutic strategy.
White, William B; Cannon, Christopher P; Heller, Simon R
BACKGROUND: To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes...... with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. METHODS: We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring...... of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. CONCLUSIONS: Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin...
Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and
Moin, S.; Gondal, G.M.G.
To measure the relation of creatinine clearance in type-2 diabetic patients with different components of metabolic syndrome and to quantify the relationship of frequency of incident CKD with increasing number of metabolic syndrome components while controlling for age, gender and duration of diabetes. Cross-sectional descriptive study. Patients having type-2 Diabetes for more than 5 years were enrolled. Information regarding age, gender, duration of diabetes, type of diabetes, treatment taking, complete fasting lipid profile, fasting blood glucose, Body Mass Index (BMI), 24 hours urinary proteins and creatinine clearance, co-existent risk factors like hypertension and ischemic heart disease was taken. Patients were divided into groups having one to all five metabolic syndrome traits. Progressive increase in the metabolic syndrome traits was compared with decline in creatinine clearance. Pearson correlation test and multiple logistic regression were applied to determine correlation with significance at r and p <0.05. Out of 104 evaluated female and male patients, 70% had hypertension, ischemic heart disease and a family history of diabetes. While 20% had normal creatinine clearance, 37% had a creatinine clearance between 60-90 ml/min, 19% had a creatinine clearance of 30-59 ml/min, 18% had a creatinine clearance of less than 30 ml/min and 10% were already in stage 5 CKD. The decline in renal function was more severe in subjects evaluated who had a higher number of features of the metabolic syndrome. Age was the only significant determinant of development of CKD (p=0.05). The renal function progressively declined with 3 or more features of the metabolic syndrome. (author)
Tekin, M; Bodurtha, J N; Nance, W E; Pandya, A
Klein-Waardenburg syndrome or Waardenburg syndrome type 3 (WS-III; MIM 148820) is characterized by the presence of musculoskeletal abnormalities in association with clinical features of Waardenburg syndrome type 1 (WS-I). Since the description of the first patient in 1947 (D. Klein, Arch Klaus Stift Vererb Forsch 1947: 22: 336-342), a few cases have been reported. Only occasional families have demonstrated autosomal-dominant inheritance of WS-III. In a previous report, a missense mutation in the paired domain of the PAX3 gene has been described in a family with dominant segregation of WS-III. In this report, we present a second family (mother and son) with typical clinical findings of WS-III segregating with a heterozygous 13-bp deletion in the paired domain of the PAX3 gene. Although homozygosity or compound heterozygosity has also been documented in patients with severe limb involvement, a consistent genotype-phenotype correlation for limb abnormalities associated with heterozygous PAX3 mutations has not previously been apparent. Heterozygous mutations could either reflect a unique dominant-negative effect or possibly the contribution of other unlinked genetic modifiers in determining the phenotype.
Gera, D N; Ghuge, P P; Gandhi, S; Vanikar, A V; Shrimali, J D; Kute, V B; Trivedi, H L
Aortic dissection (AD) is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS) without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors.
D N Gera
Full Text Available Aortic dissection (AD is a potentially life-threatening medical emergency usually encountered in the elderly. Here, we report a 9-year-old child who was incidentally detected to have asymptomatic chronic type B dissecting aneurysm of aorta when he presented with relapse of Hemolytic uremic syndrome (HUS without any genetic abnormalities like Marfan or Ehler-Danlos syndrome. To the best of our knowledge, this is the first case of AD associated with HUS in a child without any known associated genetic or inherited risk factors.
Ectodermal dysplasias (EDs) are a group of genodermatoses characterized by malformations of tissues derived from the ectoderm, including the skin, its appendages (hair, nails, sweat glands), teeth, and the breasts. Ectodermal dysplasia syndactyly syndrome (EDSS) is a rare, newly described type of ED involving syndactyly. We report 2 Yemeni siblings with typical EDSS manifestations, including bilateral, partial cutaneous syndactyly of the fingers and toes; sparse, coarse, brittle scalp hair, eyebrows, and eyelashes; and conical, widely spaced teeth with enamel notches. In addition, the siblings presented with other features hitherto not described for this syndrome, such as adermatoglyphia, onychogryphosis, hypoplastic widely spaced nipples, hypoplastic thumbs, and red scalp hair.
Full Text Available Complex regional pain syndrome type 1 (CRPS-1 is a chronic pain syndrome characterized by severe pain, swelling, autonomic dysfunction and dystrophic changes in affected extremity. RSDS is a rare disease in children and usually occurs after trauma, however, without trauma may also occur. We were detected CRPS-1 activated by cold and stress and characterized by recurrent attacks in the bilateral upper extremities in 14 year-old girl, which is similar to Raynaud’s phenomenon. We present this case with the literature because of its rarity and atypical course.
Classen, John B
There is an epidemic in children of metabolic syndrome, obesity, type 2 diabetes and other individual diseases that form the components of metabolic syndrome. Poor diet and low exercise can not explain many facets of the epidemic including the onset in children 6 month of age, the protective effect of obesity on the incidence of type 1 diabetes and the epidemic of type 2 diabetes/metabolic syndrome in grass fed horses. Poor diet and exercise also do not explain the epidemic of type 1 diabetes in children that resembles the epidemic of type 2 diabetes/metabolic syndrome. Several papers have been published to indicate that the epidemics of type 1 and type 2 diabetes/metabolic syndrome in children are linked and are polar opposite responses to iatrogenic inflammation. Several lines of research support this. Data from different races indicates that there is an inverse relationship between developing type 1 diabetes and type 2 diabetes. Races with high risk of developing type 2 diabetes have a decreased risk of developing type 1 diabetes. Data from Italy confirmed an inverse association between obesity and type 1 diabetes. Further studies indicate the inverse relationship between type 1 diabetes and type 2 diabetes/obesity is due to cortisol production. Data indicates those with low cortisol responses have a predilection for type 1 diabetes and other autoimmune disorders following inflammation, while those with high cortisol/ immune suppressive responses develop type 2 diabetes/metabolic syndrome/obesity which resembles a Cushingoid state but are spared in the autoimmune disorders. Japanese children produce much more cortisol following immunization than Caucasian children. The later explains why discontinuation of BCG vaccination was associated with a decrease in type 1 diabetes in European children and a decrease in type 2 diabetes in Japanese children. Both the epidemics of type 1 diabetes and metabolic syndrome correlate with an increase in immunization. Finally
Veissi, Masoud; Anari, Razieh; Amani, Reza; Shahbazian, Hajieh; Latifi, Seyed Mahmoud
Metabolic syndrome as a cardiovascular disease predictor, is proposed to be reduced by following a Mediterranean diet. This study was aimed to explore the relationships between metabolic syndrome and Mediterranean diet in type 2 diabetes mellitus patients. A cross-sectional study was performed on 158 type 2 diabetes mellitus patients 28-75 years old (mean age: 54.3±9.6 yrs). Fasting glucose and lipid profile were measured. Blood pressure and anthropometric characteristics of each participant were recorded. Food frequency questionnaires were evaluated using an 11-item score to determine the adherence to Mediterranean diet. Totally, 55.4% of participants had a good adherence to Mediterranean diet. The risk of metabolic syndrome in women was significantly higher than in men (OR=8.65, CI 95%=2.88-25.99; pMediterranean diet (p=0.167). Results demonstrated no association between Mediterranean diet adherence and metabolic syndrome in type 2 diabetes mellitus patients. However, nuts, legumes and seeds might have greater benefits for diabetics. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Ahmed, A.; Khan, T.E.; Yasmeen, T.; Awan, S.; Islam, N.
Objectives: To determine the frequency of metabolic syndrome in type 2 diabetes according to three commonly used operational definitions (World Health Organization(WHO), National Cholesterol Education Program Adult Treatment Panel( NCEP ATP III) and International Diabetes Federation( IDF)). To evaluate the agreement between these classifications in the Pakistani cohort. Methods: Data was collected retrospectively of 210 patients with type 2 diabetes visiting outpatient clinics of one of the large tertiary care hospitals at Karachi, Pakistan between June 2008 to November 2008. Results: The prevalence of metabolic syndrome was found to be 81.4% (WHO), 86.7 %( IDF) and 91.9 %( NCEP ATPIII). The degree of agreement (kappa statistic) was found to be highest among IDF and NCEP ATPIII (0.728) as compared to (0.436 and 0.417) between WHO and ATP and WHO and IDF respectively. The most significant predictors for metabolic syndrome were found out to be female gender OR= 8.74 95% CI 1.51-50.53, low HDL cholesterol levels OR= 0.89 95% CI 0.84-0.94 and high systolic blood pressure OR= 1.06 95% CI 1.009-1.11. Conclusion: Our study results suggested that NCEP ATPIII and IDF are the most reliable criteria for diagnosing metabolic syndrome in type 2 diabetic patients, with NECP capturing more patients in comparison to IDF definition. The alarmingly high frequency of metabolic syndrome in type 2 diabetes found in this study suggests that primary prevention strategies should be initiated earlier and early in this ethnic group and our health care system should be geared up to cope with this deadly quartet. (author)
Whitaker John K
Full Text Available Abstract Background Inferior conjunctivochalasis is common, but is rarely severe enough to require conjunctival excision. This report describes a patient with severe conjunctivochalasis who was subsequently diagnosed with Ehlers Danlos Syndrome, Classic Type. Case presentation A patient suffering from foreign body sensation, frequent blinking and bilateral inferior conjunctivochalasis was referred and treated by topical ocular lubrication. However, no improvement was observed prompting potential excision of conjunctivochalasis. Following patient consultation and clinical diagnosis including hypermobile joints and skin elasticity, poor wound healing and wide scar morphology, Ehlers-Danlos syndrome was confirmed in the patient. Conclusion This case highlights the need for direct patient questioning and provides the first reported association between conjunctiovochalasis and Ehlers-Danlos syndrome.
Full Text Available Aminoglycoside-induced renal toxicity is well known and may manifest with nonoliguric renal failure or renal tubular dysfunction. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome, or distal renal tubular acidosis. We discuss a patient who developed severe renal tubular dysfunction secondary to short-term therapy with Amikacin, resulting in refractory hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, and polyuria. This constellation of biochemical abnormalities mimic Type 5 Bartter′s syndrome, where there is activating mutation of the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule. In this case this activation of the calcium sensing receptor was triggered by amikacin. This phenomenon has been described with gentamicin though never with amikacin. Recovery of the tubular dysfunction took 15 days following cessation of the offending drug, Amikacin.
Nordestgaard, Ask Tybjærg; Thomsen, Mette; Nordestgaard, Børge Grønne
convincingly with obesity, metabolic syndrome, type 2 diabetes, body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol or glucose levels. Per-allele meta-analysed odds ratios for type 2 diabetes were 1....../diastolic blood pressure, triglycerides and total cholesterol and with low high-density lipoprotein cholesterol, but not with glucose levels. In genetic analyses, 9-10 vs 0-3 coffee-intake alleles were associated with 29% higher coffee intake. However, genetically derived high coffee intake was not associated...... to 78,021 additional individuals from the DIAGRAM consortium. RESULTS: Observationally, high coffee intake was associated with low risk of obesity, metabolic syndrome and type 2 diabetes. Further, high coffee intake was associated with high body mass index, waist circumference, weight, height, systolic...
Padoin, Alexandre Vontobel; Galvão Neto, Manoel; Moretto, Myriam; Barancelli, Fabiano; Schroer, Caroline Eckerdt; Mottin, Cláudio Corá
Dumping syndrome is one of ten most common complications in morbidly obese patients operated. Recent studies in relation to type 2 diabetes mellitus (DM2) in patients submitted to gastric bypass led us to examine the different outcomes in this group of patients. Our objective was to determine the difference in the prevalence of dumping syndrome in patients with DM2 submitted to gastric bypass. In this retrospective study, 49 diabetic and 54 non-diabetic morbidly obese patients were submitted to gastric bypass and followed up at 3, 6, and 12 months after surgery. The occurrence of dumping was determined by the patient's medical chart, where it was considered positive if recorded in at least one of three evaluations. The 103 patients evaluated had a mean BMI of 49.5 +/- 9.3 kg/m(2) and mean age of 38 +/- 9.7 years, with 75.7% being women. The prevalence of dumping syndrome in this population was 24.3%. The prevalence of dumping was greater in patients with DM2 (44.9%) when compared to the control group (5.6%; p DM2 as the only variable associated with dumping syndrome. Dumping syndrome is a common postoperative complication in gastric bypass. Patients with DM2 show a greater postoperative prevalence of dumping.
Clinical characteristics of abnormal savda syndrome type in human immunodeficiency virus infection and acquired immune deficiency syndrome patients: A cross-sectional investigation in Xinjiang, China.
Peierdun, Mi-ji-ti; Liu, Wen-xian; Renaguli, Ai-ze-zi; Nurmuhammat, Amat; Li, Xiao-chun; Gulibaier, Ka-ha-er; Ainivaer, Wu-la-mu; Halmurat, Upur
To investigate the distribution of abnormal hilit syndromes in traditional Uighur medicine (TUM) among human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) patients, and to find out the clinical characteristics of abnormal savda syndrome type HIV/AIDS patients. Between June and July in 2012, 307 eligible HIV/AIDS patients from in-patient department and out-patient clinics of Xinjiang Uighur Autonomous Region the Sixth People's Hospital in Urumqi were investigated. TUM syndrome differentiation was performed by a senior TUM physician. Each participant completed a Sign and Symptom Check-List for Persons Living with HIV/AIDS (SSC-HIV) questionnaire. Depression was evaluated by using Hamilton Rating Scale for Depression Questionnaire. Blood specimen was collected from each participant to test the levels of blood chemicals. Of 307 HIV/AIDS patients, 189 (61.6%) were abnormal savda syndrome type, 118 (38.4%) were non-abnormal-savda syndrome type. Mean CD4 counts of abnormal savda syndrome type patients was (227.61±192.93) cells/µL, and the prevalence of anemia, thrombocytopenia, and elevated cystatin C were 49.7%, 28.6%, and 44.7%, which were significantly higher than those in the non-abnormal-savda syndrome type patients (26.3%, 16.0% and 25.0%,PHIV/AIDS-related symptoms such as fatigue (42.3%), back aches (40.7%), lack of appetite (33.9%), night sweats (31.7%) were more common among abnormal savda syndrome patients (PHIV/AIDS patients, and they present a more sever clinical manifestation.
Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies. PMID:22342811
Yang, Shu-zhi; Yuan, Hui-jun; Bai, Lin-na; Cao, Ju-yang; Xu, Ye; Shen, Wei-dong; Ji, Fei; Yang, Wei-yan
To investigate detailed clinical features of a Chinese pedigree with Waardenburg syndrome type 2. Members of this pedigree were interviewed to identify personal or family medical histories of hearing loss, the use of aminoglycosides, and other clinical abnormalities by filling questionnaire. The audiological and other clinical evaluations of the proband and other members of this family were conducted, including pure-tone audiometry, immittance and auditory brain-stem response and ophthalmological, dermatologic, hair, temporal bone CT examinations. This family is categorized as Waardenburg syndrome type 2 according to its clinical features. It's an autosomal dominant disorder with incomplete penetrance. The clinical features varied greatly among family members and characterized by sensorineural hearing loss, heterochromia irides, freckle on the face and premature gray hair. Hearing loss can be unilateral or bilateral, congenital or late onset in this family. This Chinese family has some unique clinical features comparing with the international diagnostic criteria for Waardenburg syndrome. This study may provide some evidences to amend the diagnostic criteria for Waardenburg syndrome in Chinese population.
Full Text Available Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n=61, 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.
Skodova, Zuzana; Lajciakova, Petra; Banovcinova, Lubica
The aim of this study was to examine the effect of Type D personality, along with other personality traits (resilience and sense of coherence), on burnout syndrome and its counterpart, engagement, among students of nursing, midwifery, and psychology. A cross-sectional study was conducted on 97 university students (91.9% females; M age = 20.2 ± 1.49 years). A Type D personality subscale, School Burnout Inventory, Utrecht Work Engagement Scale, Sense of Coherence Questionnaire, and Baruth Protective Factor Inventory were used. Linear regression models, Student's t test, and Pearson's correlation analysis were employed. Negative affectivity, a dimension of Type D personality, was a significant personality predictor for burnout syndrome (β = .54; 95% CI = [0.33, 1.01]). The only significant personality predictor of engagement was a sense of coherence. Students who were identified as having Type D personality characteristics scored significantly higher on the burnout syndrome questionnaire (t = -2.58, p burnout. © The Author(s) 2016.
Rombaut, Lies; Deane, Janet; Simmonds, Jane; De Wandele, Inge; De Paepe, Anne; Malfait, Fransiska; Calders, Patrick
Physiotherapy plays a fundamental role in managing adults with the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). However, it is a challenge for both the patient and the physiotherapist as the condition is poorly understood and treatment for JHS/EDS-HT is currently undefined. Insight into current practice is, therefore, necessary in order to establish baseline knowledge in this area and in the long term to improve the standard of patient care. Therefore, the purpose of this study was to evaluate current physiotherapists' knowledge of JHS/EDS-HT and to gain insight into current physiotherapy practice with emphasis on assessment, management, and treatment efficacy. Three hundred twenty-five Flemish physiotherapists participated in the study by filling out electronically a modified version of the "Hypermobility and Hypermobility Syndrome Questionnaire" (HHQ), which covered theoretical constructs such as general knowledge, assessment, management, and learning in relation to generalized joint hypermobility and JHS/EDS-HT. The results show that physiotherapists report a low level of confidence with regard to assessment and management of JHS/EDS-HT. Knowledge of hypermobility and JHS/EDS-HT is weak, especially regarding the features associated with JHS/EDS-HT. Many treatment approaches are used by physiotherapists with the majority showing preference for education, reassurance, muscle strengthening, proprioceptive and core stability training. Almost all approaches were perceived as being clinically effective by the physiotherapists, highlighting a lack of consensus. In conclusion, this study in Flemish physiotherapists confirms that JHS/EDS-HT is under-recognized, not well known and deemed difficult to treat. Further education is required and sought by the physiotherapists surveyed, and future research is needed. © 2015 Wiley Periodicals, Inc.
Heckenlively, J R; Chang, B; Erway, L C; Peng, C; Hawes, N L; Hageman, G S; Roderick, T H
Usher syndrome is a group of diseases with autosomal recessive inheritance, congenital hearing loss, and the development of retinitis pigmentosa, a progressive retinal degeneration characterized by night blindness and visual field loss over several decades. The causes of Usher syndrome are unknown and no animal models have been available for study. Four human gene sites have been reported, suggesting at least four separate forms of Usher syndrome. We report a mouse model of type I Usher syndr...
Wijk, E. van; Pennings, R.J.E.; Brinke, H. te; Claassen, A.M.W.; Yntema, H.G.; Hoefsloot, L.H.; Cremers, F.P.M.; Cremers, C.W.R.J.; Kremer, J.M.J.
The USH2A gene is mutated in patients with Usher syndrome type IIa, which is the most common subtype of Usher syndrome and is characterized by hearing loss and retinitis pigmentosa. Since mutation analysis by DNA sequencing of exons 1-21 revealed only ~63% of the expected USH2A mutations, we
Chen, Ye-meng; Li, Hui; Zheng, Xin; Zhang, Qun-ce; Wang, Tian-fang
Whiplash injury is a relatively common injury of clinical acupuncture and moxibustion in the United States. The mechanism and clinical manifestation of whiplash injuries as well as its pathogenesis described in TCM were analyzed in this present article. The authors introduced the TCM syndrome differentiation of whiplash injuries and claimed that both the location and the stage of disease should be considered. For the different injury locations, the meridian musculature differentiation was applied to classify the whiplash injuries as Taiyang, Yangming, Shaoyang and Shaoyin Meridian syndromes. Considering the duration of the injury, qi stagnation and blood stasis types were classified in the acute stage and phlegm accumulation, insufficiency of the liver and kidney and qi and blood deficiencies types were classified during the chronic stage. An acupuncture protocol for whiplash injuries and typical cases were also introduced.
Alagramam, K N; Yuan, H; Kuehn, M H; Murcia, C L; Wayne, S; Srisailpathy, C R; Lowry, R B; Knaus, R; Van Laer, L; Bernier, F P; Schwartz, S; Lee, C; Morton, C C; Mullins, R F; Ramesh, A; Van Camp, G; Hageman, G S; Woychik, R P; Smith, R J; Hagemen, G S
We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.
Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L
Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.
Full Text Available Ehlers-Danlos syndrome hypermobility type a. k. a. joint hypermobility syndrome (JHS/EDS-HT is a hereditary musculoskeletal disorder associating generalized joint hypermobility with chronic pain. Anecdotal reports suggest a prominent role for kinesiophobia in disease manifestations, but no study has systematically addressed this point. Objective. To investigate the impact of kinesiophobia and its relationship with pain, fatigue, and quality of life in JHS/EDS-HT. Design. Cross-sectional study. Subjects/Patients. 42 patients (40 female and 2 male with JHS/EDS-HT diagnosis following standardized diagnostic criteria were selected. Methods. Disease features were analyzed by means of specific questionnaires and scales evaluating kinesiophobia, pain, fatigue, and quality of life. The relationships among variables were investigated using the Spearman bivariate analysis. Results. Kinesiophobia resulted predominantly in the patients’ sample. The values of kinesiophobia did not correlate with intensity of pain, quality of life, and (or the single component of fatigue. A strong correlation was discovered between kinesiophobia and general severity of fatigue. Conclusions. In JHS/EDS-HT, the onset of pain-avoiding strategies is related to the presence of pain but not to its intensity. The clear-cut correlation between kinesiophobia and severity of fatigue suggests a direct link between musculoskeletal pain and fatigue. In JHS/EDS-HT, the underlying mechanism is likely to be facilitated by primary disease characteristics, including hypotonia.
Eker, Hatice Koçak; Derinkuyu, Betül Emine; Ünal, Sevim; Masliah-Planchon, Julien; Drunat, Séverine; Verloes, Alain
Baraitser-Winter syndrome (BRWS) is a rare condition affecting the development of the brain and the face. The most common characteristics are unusual facial appearance including hypertelorism and ptosis, ocular colobomas, hearing loss, impaired neuronal migration and intellectual disability. BRWS is caused by mutations in the ACTB and ACTG1 genes. Cerebro-fronto-facial syndrome (CFFS) is a clinically heterogeneous condition with distinct facial dysmorphism, and brain abnormalities. Three subtypes are identified. We report a female infant with striking facial features and brain anomalies (included polymicrogyria) that fit into the spectrum of the CFFS type 3 (CFFS3). She also had minor anomalies on her hands and feet, heart and kidney malformations, and recurrent infections. DNA investigations revealed c.586C>T mutation (p.Arg196Cys) in ACTB. This mutation places this patient in the spectrum of BRWS. The same mutation has been detected in a polymicrogyric patient reported previously in literature. We expand the malformation spectrum of BRWS/CFFS3, and present preliminary findings for phenotype-genotype correlation in this spectrum. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Brugnara, Milena; Gaudino, Rossella; Tedeschi, Silvana; Syrèn, Marie-Louise; Perrotta, Silverio; Maines, Evelina; Zaffanello, Marco
We report the case of an infant boy with polyuria and a familial history of central diabetes insipidus. Laboratory blood tests disclosed hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Plasma magnesium concentration was slightly low. Urine analysis showed hypercalciuria, hyposthenuria, and high excretion of potassium. Such findings oriented toward type III Bartter syndrome (BSIII). Direct sequencing of the CLCNKB gene revealed no disease-causing mutations. The water deprivation test was positive. Magnetic resonance imaging showed a lack of posterior pituitary hyperintensity. Finally, direct sequencing of the AVP-NPII gene showed a point mutation (c.1884G>A) in a heterozygous state, confirming an autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). This condition did not explain the patient's phenotype; thus, we investigated for Gitelman syndrome (GS). A direct sequencing of the SLC12A3 gene showed c.269A>C and c.1205C>A new mutations. In conclusion, the patient had a genetic combination of GS and adFNDI with a BSIII-like phenotype.
Lee, Yeon Hee; Cho, Whi Youl; Kim, Myung Soon; Hong, In Soo; Sung, Ki Joon; Yang, Jae Seung [Wonju College of Medicine, Yonsei University, Wonju (Korea, Republic of)
Apert syndrome (Acrocephalosyndactyly type 1) is a rare congenital anomaly characterized by craniosynosis and symmetric-syndactyly of both extremities. Radiological examination of the skull shows hydrocephalus due to aqueductal stenosis. In the facial bones, the hypoplastic maxilla and relatively prominent mandible are observed associated with other anomalies such as cleft palate. Radiologic examination of both hands and feet show bony or subcutaneous syndactylism and typical mitten hands and webbed toes.
Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo
Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism. PMID:27081571
Hite, S.H.; Krivit, W.; Haines, S.J.; Whitley, C.B.
We present the imaging findings in a patient with mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) who developed holocord syringomyelia. This represents the only reported case of syrinx formation in a child with MPS VI. Clinical, neurologic and spinal magnetic resonance imaging findings are presented. The patient has maintained a stable clinical and neurologic course over the period following allogeneic bone marrow transplant. (orig.). With 3 figs
Conclusions: Our data showed that firstly higher vitamin D status is inversely associated with fasting glycemia, and secondly serum 25(OHD3 predicts MeS risk in the subjects with T2D. Demonstrating the association of hypovitaminosis D with disorders of glucose metabolism and higher risk for development of further complications, notably CVD, may lead to a new target for preventive efforts at the population level. Keywords: Vitamin D, Type 2 diabetes, Metabolic syndrome, Cardiovascular disease
Full Text Available We describe a case of a 26 years old man who presented with adrenocortical insufficiency followed by hypoparathyroidism and subsequently mucocutaneous candidiasis. He also had nail dystrophy, cataract and alopecia, but no other endocrinopathies. He was diagnosed as a case of autoimmune polyendocrine syndrome type 1(APS 1. APS1 is a rare endocrine disorder and only a few cases have been reported from Bangladesh. IMC J Med Sci 2016; 10(1: 33-35
Lee, Yeon Hee; Cho, Whi Youl; Kim, Myung Soon; Hong, In Soo; Sung, Ki Joon; Yang, Jae Seung
Apert syndrome (Acrocephalosyndactyly type 1) is a rare congenital anomaly characterized by craniosynosis and symmetric-syndactyly of both extremities. Radiological examination of the skull shows hydrocephalus due to aqueductal stenosis. In the facial bones, the hypoplastic maxilla and relatively prominent mandible are observed associated with other anomalies such as cleft palate. Radiologic examination of both hands and feet show bony or subcutaneous syndactylism and typical mitten hands and webbed toes
Ruzic, B.; Bosnar, B.; Beleznay, O.
Case report of a very rare case of Holt-Oram-Syndrome (in a seven months old baby) associated with tricuspid atresia (itself a rare condition of isolated congenital heart desease) and anomalous return of pulmonary vein into the right atrium. According to the classification based on anatomy, our case corresponds to type Ia. The diagnosis was confirmed clinically, electrocardiographically, radiologically and angiographically. (orig.) [de
Bjørnshave, Ann; Hermansen, Kjeld
The incidence of the metabolic syndrome (MetS) and type 2 diabetes (T2D) is increasing worldwide. Evidence supports a negative relationship between the consumption of dairy products and risk of MetS and T2D. Dairy proteins are known to have a directly beneficial effect on hypertension, dyslipidemia, and hyperglycemia, but a detailed understanding of the underlying mechanisms is missing. It has been confirmed by observations that the insulinotropic effect of dairy proteins is associated with t...
Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo
Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism.
Yoshida, Yu; Doi, Rieko; Adachi, Kaori; Nanba, Eiji; Kodani, Isamu; Ryoke, Kazuo
Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant disorder characterized by hair hypopigmentation, abnormal iris pigmentation, and congenital hearing loss. WS1 is caused by mutations in paired box gene 3 (PAX3). We identified a novel PAX3 mutation (c.1107 C>G, p.Ser369Arg) in a Japanese WS1 patient showing abnormal right iris pigmentation, right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism.
Colombo, L; Sala, B; Montesano, G; Pierrottet, C; De Cillà, S; Maltese, P; Bertelli, M; Rossetti, L
To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), axial length (AL), automated visual field (VF), and EDI OCT. Both retinal and choroidal measures were measured. Statistical analysis was performed to correlate choroidal thickness with age, BCVA, IOP, AL, VF, and RT. Comparison with data about healthy people and nonsyndromic RP patients was performed. Results. Mean subfoveal choroidal thickness (SFCT) was 248.21 ± 79.88 microns. SFCT was statistically significant correlated with age (correlation coefficient -0.7248179, p patients (p = 0.2138). Conclusions. Our study demonstrated in vivo choroidal thickness reduction in patients with Usher Syndrome type 2. These data are important for the comprehension of mechanisms of disease and for the evaluation of therapeutic approaches.
Quade, Annegret; Wiesmann, Martin; Weis, Joachim; Kurth, Ingo; Jalaie, Houman; Rohrbach, Marianne; Häusler, Martin
Patients with the kyphoscoliotic type of Ehlers-Danlos syndrome have an increased risk of vascular complications such as aortic dissection and perforation. Cerebral ischemia has only rarely been documented. This 13-year-old girl with the kyphoscoliotic type of Ehlers-Danlos syndrome experienced a large right middle cerebral artery distribution infarction. Full intravenous heparinization was started in response to presumed arterial dissection. Magnetic resonance imaging studies including magnetic resonance angiography and digital subtraction angiography, however, did not confirm dissection but suggested with cerebral vasculitis extending from the intradural right internal carotid artery to the M2 branches of the middle cerebral artery. Combined steroid and cyclophosphamide therapy was associated with clinical improvement. Two months later she died from hemorrhagic shock caused by a two-sided spontaneous rupture of the aortic artery. Cerebral vasculitis should be included in the differential diagnosis of vascular complications in kyphoscoliotic type of Ehlers-Danlos syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA, intraocular pressure (IOP, axial length (AL, automated visual field (VF, and EDI OCT. Both retinal and choroidal measures were measured. Statistical analysis was performed to correlate choroidal thickness with age, BCVA, IOP, AL, VF, and RT. Comparison with data about healthy people and nonsyndromic RP patients was performed. Results. Mean subfoveal choroidal thickness (SFCT was 248.21±79.88 microns. SFCT was statistically significant correlated with age (correlation coefficient −0.7248179, p<0.01. No statistically significant correlation was found between SFCT and BCVA, IOP, AL, VF, and RT. SFCT was reduced if compared to healthy subjects (p<0.01. No difference was found when compared to choroidal thickness from nonsyndromic RP patients (p=0.2138. Conclusions. Our study demonstrated in vivo choroidal thickness reduction in patients with Usher Syndrome type 2. These data are important for the comprehension of mechanisms of disease and for the evaluation of therapeutic approaches.
Lee, Sunghee; Lee, Seung Ku; Kim, Jong Yeol; Cho, Namhan; Shin, Chol
To examine whether the use of Sasang constitutional (SC) types, such as Tae-yang (TY), Tae-eum (TE), So-yang (SY), and So-eum (SE) types, increases the accuracy of risk prediction for metabolic syndrome. From 2001 to 2014, 3529 individuals aged 40 to 69 years participated in a longitudinal prospective cohort. The Cox proportional hazard model was utilized to predict the risk of developing metabolic syndrome. During the 14 year follow-up, 1591 incident events of metabolic syndrome were observed. Individuals with TE type had higher body mass indexes and waist circumferences than individuals with SY and SE types. The risk of developing metabolic syndrome was the highest among individuals with the TE type, followed by the SY type and the SE type. When the prediction risk models for incident metabolic syndrome were compared, the area under the curve for the model using SC types was significantly increased to 0.8173. Significant predictors for incident metabolic syndrome were different according to the SC types. For individuals with the TE type, the significant predictors were age, sex, body mass index (BMI), education, smoking, drinking, fasting glucose level, high-density lipoprotein (HDL) cholesterol level, systolic and diastolic blood pressure, and triglyceride level. For Individuals with the SE type, the predictors were sex, smoking, fasting glucose, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level, while the predictors in individuals with the SY type were age, sex, BMI, smoking, drinking, total cholesterol level, fasting glucose level, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level. In this prospective cohort study among 3529 individuals, we observed that utilizing the SC types significantly increased the accuracy of the risk prediction for the development of metabolic syndrome.
Vieira, Bruna Angelo; Luft, Vivian Cristine; Schmidt, Maria Inês; Chambless, Lloyd Ellwood; Chor, Dora; Barreto, Sandhi Maria; Duncan, Bruce Bartholow
The prevalence of the metabolic syndrome is rising worldwide. Its association with alcohol intake, a major lifestyle factor, is unclear, particularly with respect to the influence of drinking with as opposed to outside of meals. We investigated the associations of different aspects of alcohol consumption with the metabolic syndrome and its components. In cross-sectional analyses of 14,375 active or retired civil servants (aged 35–74 years) participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we fitted logistic regression models to investigate interactions between the quantity of alcohol, the timing of its consumption with respect to meals, and the predominant beverage type in the association of alcohol consumption with the metabolic syndrome. In analyses adjusted for age, sex, educational level, income, socioeconomic status, ethnicity, smoking, body mass index, and physical activity, light consumption of alcoholic beverages with meals was inversely associated with the metabolic syndrome (≤4 drinks/week: OR = 0.85, 95%CI 0.74–0.97; 4 to 7 drinks/week: OR = 0.75, 95%CI 0.61–0.92), compared to abstention/occasional drinking. On the other hand, greater consumption of alcohol consumed outside of meals was significantly associated with the metabolic syndrome (7 to 14 drinks/week: OR = 1.32, 95%CI 1.11–1.57; ≥14 drinks/week: OR = 1.60, 95%CI 1.29–1.98). Drinking predominantly wine, which occurred mostly with meals, was significantly related to a lower syndrome prevalence; drinking predominantly beer, most notably when outside of meals and in larger quantity, was frequently associated with a greater prevalence. In conclusion, the alcohol—metabolic syndrome association differs markedly depending on the relationship of intake to meals. Beverage preference—wine or beer—appears to underlie at least part of this difference. Notably, most alcohol was consumed in metabolically unfavorable type and timing. If further investigations
Mazzocco, Michele M. M.
This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…
Bain, Anna; Stewart, Munro; Mwamure, Peter; Nirmalaraj, Kingsley
A 57-year-old Caucasian woman with known autoimmune hypothyroidism diagnosed in 2006 presented to hospital with flu-like symptoms and circulatory collapse. She reported weight loss and gradual increase in her skin pigmentation over a 1-year period. Aggressive fluid resuscitation was instituted. Hormonal tests showed primary adrenal insufficiency. Appropriate steroid replacement was started with rapid clinical response. Subsequent antibody tests confirmed the diagnosis of autoimmune polyglandular type 2 (Schmidt's) syndrome. The adrenal crisis had been precipitated by influenza virus type B infection. 2015 BMJ Publishing Group Ltd.
Wang, C; Kim, E; Attaie, A; Smith, T N; Wilcox, E R; Lalwani, A K
Waardenburg Syndrome (WS) is an autosomal-dominant disorder phenotypically characterized by sensorineural hearing loss and pigmentary disturbances. Presence of dystopia canthorum is indicative of WS type 1 and results from defects in the PAX3 gene, whereas normally located medial canthi is characteristic of type 2 WS (WS2) and is associated with defects in the microphthalmia-associated transcription factor (MIFT) gene. Here a neutral polymorphism is reported in the PAX3 gene (T315K) in a family with WS2. Copyright 1998 Academic Press Limited
Preeti, Jois; Alexandre, Mebazaa; Pupalan, Iyngkaran; Merlin, Thomas C.; Claudio, Ronco
The most important advancements in the Cardiorenal syndrome (CRS) are its definition and subsequent classifications. When the predominant pathology and pathophysiology is the heart, i.e. chronic heart failure (CHF), and where any renal impairment (RI) subsequent to this is secondary, the classification is type 2 CRS. There are unique differences in the pathophysiology and progression of individual subclasses. It is important to understand the evolution of CHF and consequences of subsequent RI as they are becoming increasingly prevalent, aggravate morbidity and mortality and limit many therapeutic options. In this paper we discuss the significance of the type 2 CRS patients in the context of the thematic series. PMID:27280302
Rylski, Bartosz; Bavaria, Joseph E; Beyersdorf, Friedhelm; Branchetti, Emanuela; Desai, Nimesh D; Milewski, Rita K; Szeto, Wilson Y; Vallabhajosyula, Prashanth; Siepe, Matthias; Kari, Fabian A
Data on outcomes after Stanford type A aortic dissection in patients with Marfan syndrome are limited. We investigated the primary surgery and long-term results in patients with Marfan syndrome who suffered aortic dissection. Among 1324 consecutive patients with aortic dissection type A, 74 with Marfan syndrome (58% men; median age, 37 years [first and third quartiles, 29 and 48 years]) underwent surgical repair (85% acute dissections; 68% DeBakey I; 55% composite valved graft, 30% supracoronary ascending replacement, 15% valve-sparing aortic root replacement; 12% total arch replacement; 3% in-hospital mortality) at 2 tertiary centers in the United States and Europe over the past 25 years. The rate of aortic reintervention with resternotomy was 24% (18 of 74) and of descending aorta (thoracic+abdominal) intervention was 30% (22 of 74) at a median follow-up of 8.4 years (first and third quartiles, 2.2 and 12.7 years). Freedom from need for aortic root reoperation in patients who underwent primarily a composite valved graft or valve-sparing aortic root replacement procedure was 95±3%, 88±5%, and 79±5% and in patients who underwent supracoronary ascending replacement was 83±9%, 60±13%, 20±16% at 5, 10, and 20 years. Secondary aortic arch surgery was necessary only in patients with initial hemi-arch replacement. Emergency surgery for type A dissection in patients with Marfan syndrome is associated with low in-hospital mortality. Failure to extend the primary surgery to aortic root or arch repair leads to a highly complex clinical course. Aortic root replacement or repair is highly recommended because supracoronary ascending replacement is associated with a high need (>40%) for root reintervention.
Zeng, Lei; Zeng, Cheng; Tao, Li-Li
To observe the therapeutic efficacy of Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation or unipolar electrocoagulation drilling technique under laparoscope for treating clomiphene-resistant polycystic ovary syndrome (PCOS). Forty infertility patients with clomiphene-resistant PCOS were assigned to two groups using stratified random sampling method according to age, infertility time, and body mass index, 20 in each group. Patients in Group A were treated with Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation, while those in Group B were treated with Chinese medical syndrome typing and treatment combined unipolar electrocoagulation drilling technique. After operation Chinese herbal treatment was administered to all patients according to syndrome typing. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), androgen (T), estradiol (E2), and prolactin (PRL) were determined before and after operation. The ovulation was monitored. The pregnancy rate and the pregnancy outcomes were recorded after operation. There was no statistical difference in the 3-month spontaneous ovulation rate or the 1-year pregnancy rate (P > 0.05). The levels of LH, T, and PRL were significantly lower after operation than before operation in the two groups (P typing and treatment combined cold needle puncture drainage operation or unipolar electrocoagulation drilling technique could effectively promote the ovulation. The two methods showed similar therapeutic effects.
Bertolasi, Laura; Frasson, Emma; Cappelletti, Jee Yun; Vicentini, Silvana; Bordignon, Monia; Graziottin, Alessandra
To investigate whether botulinum neurotoxin type A improves vaginismus and study its efficacy with repeated treatments. Outpatients were referred because standard cognitive-behavioral and medical treatment for vaginismus and vulvar vestibular syndrome failed. From this group, we prospectively recruited consecutive women (n=39) whose diagnostic electromyogram (EMG) recordings from the levator ani muscle showed hyperactivity at rest and reduced inhibition during straining. These women were followed for a mean (+/-standard deviation) of 105 (+/-50) weeks. Recruited patients underwent repeated cycles of botulinum neurotoxin type A injected into the levator ani under EMG guidance and EMG monitoring thereafter. At enrollment and 4 weeks after each cycle, women were asked about sexual intercourse; underwent EMG evaluation and examinations to grade vaginal resistance according to Lamont; and completed a visual analog scale (VAS) for pain, the Female Sexual Function Index Scale, a quality-of-life questionnaire (Short-Form 12 Health Survey), and bowel and bladder symptom assessment. At 4 weeks after the first botulinum neurotoxin type A cycle, the primary outcome measures (the possibility of having sexual intercourse, and levator ani EMG hyperactivity) both improved, as did the secondary outcomes, Lamont scores, VAS, Female Sexual Function Index Scales, Short-Form 12 Health Survey, and bowel-bladder symptoms. These benefits persisted through later cycles. When follow-up ended, 63.2% of the patients completely recovered from vaginismus and vulvar vestibular syndrome, 15.4% still needed reinjections (censored), and 15.4% had dropped out. Botulinum neurotoxin type A is an effective treatment option for vaginismus secondary to vulvar vestibular syndrome refractory to standard cognitive-behavioral and medical management. After patients received botulinum neurotoxin type A, their sexual activity improved and reinjections provided sustained benefits. III.
Fishman, Gerald A; Bozbeyoglu, Simge; Massof, Robert W; Kimberling, William
To evaluate the natural course of visual field loss in patients with Type 2 Usher syndrome and different patterns of visual field loss. Fifty-eight patients with Type 2 Usher syndrome who had at least three visual field measurements during a period of at least 3 years were studied. Kinetic visual fields measured on a standard calibrated Goldmann perimeter with II4e and V4e targets were analyzed. The visual field areas in both eyes were determined by planimetry with the use of a digitalizing tablet and computer software and expressed in square inches. The data for each visual field area measurement were transformed to a natural log unit. Using a mixed model regression analysis, values for the half-life of field loss (time during which half of the remaining field area is lost) were estimated. Three different patterns of visual field loss were identified, and the half-life time for each pattern of loss was calculated. Of the 58 patients, 11 were classified as having pattern type I, 12 with pattern type II, and 14 with pattern type III. Of 21 patients whose visual field loss was so advanced that they could not be classified, 15 showed only a small residual central field (Group A) and 6 showed a residual central field with a peripheral island (Group B). The average half-life times varied between 3.85 and 7.37 for the II4e test target and 4.59 to 6.42 for the V4e target. There was no statistically significant difference in the half-life times between the various patterns of field loss or for the test targets. The average half-life times for visual field loss in patients with Usher syndrome Type 2 were statistically similar among those patients with different patterns of visual field loss. These findings will be useful for counseling patients with Type 2 Usher syndrome as to their prognosis for anticipated visual field loss.
Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique
Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.
Wiviott, Stephen D; de Lemos, James A; Morrow, David A
The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.
Zein, Wadih M; Falsini, Benedetto; Tsilou, Ekaterina T; Turriff, Amy E; Schultz, Julie M; Friedman, Thomas B; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Muskett, Julie A; Rehman, Atteeq U; Morell, Robert J; Griffith, Andrew J; Sieving, Paul A
Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG. Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Sadeghi, André M; Cohn, Edward S; Kimberling, William J; Halvarsson, Glenn; Möller, Claes
The purpose of this study was to compare the genotype/phenotype relationship between siblings with identical USH2A pathologic mutations and the consequent audiologic phenotypes, in particular degree of hearing loss (HL). Decade audiograms were also compared among two groups of affected subjects with different mutations of USH2A. DNA samples from patients with Usher syndrome type II were analysed. The audiological features of patients and affected siblings with USH2A mutations were also examined to identify genotype-phenotype correlations. Genetic and audiometric examinations were performed in 18 subjects from nine families with Usher syndrome type IIA. Three different USH2A mutations were identified in the affected subjects. Both similarities and differences of the auditory phenotype were seen in families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found the group of affected subjects with different pathological mutations. Our results indicate that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables, such as modifying genes, epigenetics or environmental factors which may be of importance for better understanding the etiology of Usher syndrome.
Fernández, Raquel M; Núñez-Ramos, Raquel; Enguix-Riego, M Valle; Román-Rodríguez, Francisco José; Galán-Gómez, Enrique; Blesa-Sánchez, Emilio; Antiñolo, Guillermo; Núñez-Núñez, Ramón; Borrego, Salud
Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases. © 2013 Wiley Periodicals, Inc.
Choi, Joong Hyuk; Moon, Sung-Kyun; Lee, Ki Hwang; Lew, Ho Min; Chang, Yoon-Hee
Waardenburg syndrome (WS) is a rare, autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary disturbances of the skin, hair, and iris, and other developmental defects such as lateral displacement of both medial canthi and lacrimal puncta called dystopia canthorum. While mutations of the PAX3 (paired box) gene have been identified in about 99% of WS type 1 cases, WS type 2 is a heterogeneous group, with about 15% of cases caused by mutations in microphthalmia associated transcription factor (MITF). We have experienced three cases of typical WS type 2 in a Korean family, for whom full ocular examination and genetic studies were performed. The genetic studies revealed no mutation in either PAX3 or MITF genes. The genetic basis, as yet unknown for most cases of WS type 2, might be found with further investigation.
Boettcher, Claudia; Brosig, Burkhard; Zimmer, Klaus P; Wudy, Stefan A
Wolfram syndrome (also known as DIDMOAD = diabetes insipidus, diabetes mellitus, optic atrophy, deafness) is an autosomal recessive disorder characterized by the association of childhood non-immune insulin-dependent diabetes mellitus (DM) with progressive bilateral optic atrophy. Additional symptoms including signs of severe neurodegeneration and psychiatric illness are likely to evolve over time resulting in premature death. We report on two siblings of Turkish origin from our diabetes clinic who were diagnosed with Wolfram syndrome after 6 years and 2 years duration of DM, respectively. Subtle symptoms such as attitude changes, growing reading difficulties in the history of children or adolescents with antibody negative and ketone negative DM should alert the treating physician and lead to re-evaluation of the diagnosis, keeping in mind that not all juvenile DM is type 1 DM.
Full Text Available Ehlers-Danlos syndrome type VIII (EDS-VIII is a very rare autosomal dominant disease characterized by early-onset periodontitis associated with features of Ehlers-Danlos syndrome. We report a 32-year-old man whose chronic leg ulcer led to the diagnosis of EDS-VIII. He had severe periodontitis with complete loss of permanent teeth and skin fragility with thin skin, atrophic scars, and brownish atrophic pretibial plaques. Leg ulcer is not a prominent feature of EDS-VIII. We suggest adding EDS-VIII to the list of rare diseases accounting for chronic leg ulcers, if this case report prompts others to report leg ulcers associated with EDS-VIII.
Preza, Paul M; Hurtado, Abdías; Armas, Victoria; Cárcamo, César P
This study sought to evaluate the incidence of cardiorenal syndrome (CRS) type 1 in a coronary care unit and its association with hospital mortality within 30 days of admission, as well as other epidemiological characteristics. The medical records of all the patients who were hospitalized with the diagnosis of acute heart failure in a 4-year period were reviewed. CRS type 1 was characterized by the presence of acute heart failure and an elevation of serum creatinine ≥0.3mg/dL in comparison to the baseline creatinine calculated by the MDRD75 equation and/or the elevation of ≥50% of the admission serum creatinine within a 48 h period. The incidence of CRS type 1 was 27.87%, 95% CI: 20.13-36.71 (34 of 122). There was a higher frequency of CRS type 1 in those patients who were admitted with the diagnosis of cardiogenic shock (adjusted RR 2.02, 95% CI: 1.20-3.93, p=0.0378) and in those with higher hemoglobin levels (p=0.0412). The CRS type 1 was associated with an increase of 30-day mortality (HR: 4.11, 95% CI: 1.20-14.09, p=0.0244). The incidence of CRS type 1 in the coronary care unit found in our study is similar to those found in foreign studies. The history of stroke and the higher values of hemoglobin were associated with a higher incidence of cardiorenal syndrome type 1. Patients with CRS type 1 had a higher hospital mortality within 30 days of admission. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.
Di Stefano, G; Celletti, C; Baron, R; Castori, M; Di Franco, M; La Cesa, S; Leone, C; Pepe, A; Cruccu, G; Truini, A; Camerota, F
Patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia. In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres. Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio. While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms. WHAT DOES THIS STUDY ADD?: In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain. © 2016 European Pain Federation - EFIC®
Castori, Marco; Dordoni, Chiara; Morlino, Silvia; Sperduti, Isabella; Ritelli, Marco; Valiante, Michele; Chiarelli, Nicola; Zanca, Arianna; Celletti, Claudia; Venturini, Marina; Camerota, Filippo; Calzavara-Pinton, Piergiacomo; Grammatico, Paola; Colombi, Marina
Cutaneous manifestations are a diagnostic criterion of Ehlers-Danlos syndrome, hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). These two conditions, originally considered different disorders, are now accepted as clinically indistinguishable and often segregate as a single-familial trait. EDS-HT and JHS are still exclusion diagnoses not supported by any specific laboratory test. Accuracy of clinical diagnosis is, therefore, crucial for appropriate patients' classification and management, but it is actually hampered by the low consistency of many applied criteria including the cutaneous one. We report on mucocutaneous findings in 277 patients with JHS/EDS-HT with both sexes and various ages. Sixteen objective and five anamnestic items were selected and ascertained in two specialized outpatient clinics. Feature rates were compared by sex and age by a series of statistical tools. Data were also used for a multivariate correspondence analysis with the attempt to identify non-causal associations of features depicting recognizable phenotypic clusters. Our findings identified a few differences between sexes and thus indicated an attenuated sexual dimorphism for mucocutaneous features in JHS/EDS-HT. Ten features showed significantly distinct rates at different ages and this evidence corroborated the concept of an evolving phenotype in JHS/EDS-HT also affecting the skin. Multivariate correspondence analysis identified three relatively discrete phenotypic profiles, which may represent the cutaneous counterparts of the three disease phases previously proposed for JHS/EDS-HT. These findings could be used for revising the cutaneous criterion in a future consensus for the clinical diagnosis of JHS/EDS-HT. © 2015 Wiley Periodicals, Inc.
Scheper, M C; Pacey, V; Rombaut, L; Adams, R D; Tofts, L; Calders, P; Nicholson, L L; Engelbert, R H H
Lowered pressure-pain thresholds have been demonstrated in adults with Ehlers-Danlos syndrome hypermobility type (EDS-HT), but whether these findings are also present in children is unclear. Therefore, the objectives of the study were to determine whether generalized hyperalgesia is present in children with hypermobility syndrome (HMS)/EDS-HT, explore potential differences in pressure-pain thresholds between children and adults with HMS/EDS-HT, and determine the discriminative value of generalized hyperalgesia. Patients were classified in 1 of 3 groups: HMS/EDS-HT, hypermobile (Beighton score ≥4 of 9), and healthy controls. Descriptive data of age, sex, body mass index, Beighton score, skin laxity, and medication usage were collected. Generalized hyperalgesia was quantified by the average pressure-pain thresholds collected from 12 locations. Confounders collected were pain locations/intensity, fatigue, and psychological distress. Comparisons between children with HMS/EDS-HT and normative values, between children and adults with HMS/EDS-HT, and corrected confounders were analyzed with multivariate analysis of covariance. The discriminative value of generalized hyperalgesia employed to differentiate between HMS/EDS-HT, hypermobility, and controls was quantified with logistic regression. Significantly lower pressure-pain thresholds were found in children with HMS/EDS-HT compared to normative values (range -22.0% to -59.0%; P ≤ 0.05). When applying a threshold of 30.8 N/cm 2 for males and 29.0 N/cm 2 for females, the presence of generalized hyperalgesia discriminated between individuals with HMS/EDS-HT, hypermobility, and healthy controls (odds ratio 6.0). Children and adults with HMS/EDS-HT are characterized by hypermobility, chronic pain, and generalized hyperalgesia. The presence of generalized hyperalgesia may indicate involvement of the central nervous system in the development of chronic pain. © 2016, American College of Rheumatology.
Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Dordoni, Chiara; Ritelli, Marco; Venturini, Marina; Castori, Marco; Colombi, Marina
Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients.
Morlino, Silvia; Dordoni, Chiara; Sperduti, Isabella; Venturini, Marina; Celletti, Claudia; Camerota, Filippo; Colombi, Marina; Castori, Marco
Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two overlapping heritable disorders (JHS/EDS-HT) recognized by separated sets of diagnostic criteria and still lack a confirmatory test. This descriptive research was aimed at better characterizing the clinical phenotype of JHS/EDS-HT with focus on available diagnostic criteria, and in order to propose novel features and assessment strategies. One hundred and eighty-nine (163 females, 26 males; age: 2-73 years) patients from two Italian reference centers were investigated for Beighton score, range of motion in 21 additional joints, rate and sites of dislocations and sprains, recurrent soft-tissue injuries, tendon and muscle ruptures, body mass index, arm span/height ratio, wrist and thumb signs, and 12 additional orthopedic features. Rough rates were compared by age, sex, and handedness with a series of parametric and non-parametric tools. Multiple correspondence analysis was carried out for possible co-segregations of features. Beighton score and hypermobility at other joints were influenced by age at diagnosis. Rate and sites of joint instability complications did not vary according to age at diagnosis except for soft-tissue injuries. No major difference was registered by sex and dominant versus non-dominant body side. At multiple correspondence analysis, selected features tend to co-segregate in a dichotomous distribution. Dolichostenomelia and arachnodactyly segregated independently. This study pointed out a more protean musculoskeletal phenotype than previously considered according to available diagnostic criteria for JHS/EDS-HT. Our findings corroborated the need for a re-thinking of JHS/EDS-HT on clinical grounds in order to find better therapeutic and research strategies. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a hereditary connective tissue disorder affecting every bodily system. It is largely underdiagnosed by many practitioners, with the result of a considerable delay in diagnosis and, consequently, in the onset of adequate management schedule and treatment. Patients may also experience to be misbelieved, erroneously considered affected by a psychiatric or psychosomatic disorders, and rejected by the medical profession, which can lead to feelings of anger and resentment. Patient journeys are often long and complicated, but if doctors allowed the patient time to tell the full story, and were more prepared to think holistically, there may be a far more positive outcome. Here, the patients' perspective is presented with a narrative medicine approach, illustrating the tri-dimensional experience of a JHS/EDS-HT patient, who is also a Bowen Practitioner and a medical writer/educator. Narrative medicine would be invaluable in working with JHS/EDS-HT so that the patient can tell the story, and offer the practitioner a whole picture of her/his suffering and, often, the key for understanding the cause(s). Once this has been achieved, it might be possible to build upon a more positive and therapeutic dialogue which would result in better treatment and more effective management. It is also important for doctors to communicate with JHS/EDS-HT experts who will ultimately improve the patient journey and treatment outcomes of such a complex connective tissue disorder. © 2015 Wiley Periodicals, Inc.
Seyedahmadi, Babak Jian; Rivolta, Carlo; Keene, Julia A; Berson, Eliot L; Dryja, Thaddeus P
A screen of the entire coding region of the USH2A gene in 129 unrelated patients with Usher syndrome type II (USH2) and in 146 unrelated patients with non-syndromic autosomal recessive retinitis pigmentosa (ARRP) uncovered 54 different sequence variations, including 18 likely pathogenic mutations (13 frameshift, three nonsense, and two missense), 12 changes of uncertain pathogenicity (11 missense changes and one in-frame deletion), and 24 non-pathogenic rare variants or polymorphisms. Of the 18 likely pathogenic mutations, nine were novel. Among the USH2 patients, 50 (39%) had one or two likely pathogenic mutations. The most common mutant allele in USH2 patients was E767fs, which was found in 29 patients, including one homozygote. Among the ARRP patients, we found 17 (12%) with one or two likely pathogenic mutations. The most common mutant allele in ARRP patients was C759F and it was found in 10 patients. The C759F allele was also found in two USH2 patients; in neither of them was a change in the other allele found. The second most common mutant allele in both patient groups was L1447fs (found in 6/50 USH2 patients and 6/17 ARRP patients). Of the 50+17=67 patients with identified USH2A mutations, only one mutation in one allele was found in 41+12=53 (79%); the reason for the high proportion of patients with only one identified mutation is obscure. Our results indicate that USH2A mutations are found in about 7% of all cases of RP in North America, a frequency similar to the RPGR gene (8%) and the rhodopsin gene (10%).
Jaijo, Teresa; Oshima, Aki; Aller, Elena; Carney, Carol; Usami, Shin-ichi; Millán, José M; Kimberling, William J
PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation. Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15. Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8%) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2%). Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.
Full Text Available Background. Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT, is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods. The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results. Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.
Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano
Background . Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods . The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results . Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.
Full Text Available Objective To investigate the relationship between Eczema TCM syndrome types and TCM constitutional. Methods 100 cases of eczema were randomly selected and numbered, then sum up the results of report after using DSO1- A system that collect lingual, facial and sphygmic to identify the types of TCM constitution. Finally, the results were analyzed. Results The results show that the nine types of moderate physical quality account for 58.3% of spreading damp-heat pattern , Phlegm-dampness constitution 25.7% of the pattern of spleen vacuity with damp-heat, and yin deficiency 32.1% of the pattern of blood vacuity and wind-dryness. Conclusion There was a correlation between Eczema TCM syndrome types and TCM constitutional. Spreading damp-heat pattern was associated with moderate physical quality. The pattern of spleen vacuity with damp-heat was connected to Phlegm-dampness constitution. The pattern of blood vacuity and wind-dryness had relation with yin deficiency.
Makharia, Govind K; Tandon, Nikhil; Stephen, Neil de Jesus Rangel; Gupta, Siddhartha Datta; Tandon, Rakesh K
Chronic diarrhea and steatorrhea occur frequently in patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been reported earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia, one of whom had symptomatic protein-losing enteropathy.
Jukkola, A; Kauppila, S; Risteli, L; Vuopala, K; Risteli, J; Leisti, J; Pajunen, L
We describe the clinical findings and biochemical features of a male child suffering from a so far undescribed lethal connective tissue disorder characterised by extreme hypermobility of the joints, lax skin, cataracts, severe growth retardation, and insufficient production of type I and type III procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy syndrome, and geroderma osteodysplastica, as these disorders show some symptoms and signs shared with our patient. The chi...
De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane
The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Kim, Jeong Gyun; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Jeong Eun
Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure.
Full Text Available Ehlers-Danlos syndrome (EDS is a group of connective tissue disorders which are divided into various distinguishable phenotypes. The type of EDS determines the potential obstetric complications. Due to the spectrum of clinical manifestation and overlap between phenotypes, there are no standardised obstetric management guidelines. Existing literature illustrates different obstetric management in hypermobility type of EDS, including uneventful term vaginal deliveries as well as preterm cesarean section deliveries. This paper discusses obstetric management of a woman with EDS hypermobility type. Cesarean section was deemed the most appropriate delivery method in this patient due to the possible complications including risk of joint dislocation and pain morbidity. No obstetric complications were experienced, and good maternal and neonatal outcomes were achieved.
Kim, Jeong Gyun; Cho, Won-Sang; Kim, Jeong Eun
Ehlers-Danlos syndrome (EDS) is a rare inherited connective disease. Among several subgroups, type IV EDS is frequently associated with spontaneous catastrophic bleeding from a vascular fragility. We report on a case of carotid-cavernous fistula (CCF) in a patient with type IV EDS. A 46-year-old female presented with an ophthalmoplegia and chemosis in the right eye. Subsequently, seizure and cerebral infarction with micro-bleeds occurred. CCF was completely occluded with transvenous coil embolization without complications. Thereafter, the patient was completely recovered. Transvenous coil embolization can be a good treatment of choice for spontaneous CCF with type IV EDS. However, every caution should be kept during invasive procedure. PMID:24653803
Full Text Available Mirizzi syndrome (MS is an impacted stone in the cystic duct or Hartmann’s pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests.
Hartel, B P; Agterberg, M J H; Snik, A F; Kunst, H P M; van Opstal, A J; Bosman, A J; Pennings, R J E
Usher syndrome is the leading cause of hereditary deaf-blindness. Most patients with Usher syndrome type IIa start using hearing aids from a young age. A serious complaint refers to interference between sound localisation abilities and adaptive sound processing (compression), as present in today's hearing aids. The aim of this study was to investigate the effect of advanced signal processing on binaural hearing, including sound localisation. In this prospective study, patients were fitted with hearing aids with a nonlinear (compression) and linear amplification programs. Data logging was used to objectively evaluate the use of either program. Performance was evaluated with a speech-in-noise test, a sound localisation test and two questionnaires focussing on self-reported benefit. Data logging confirmed that the reported use of hearing aids was high. The linear program was used significantly more often (average use: 77%) than the nonlinear program (average use: 17%). The results for speech intelligibility in noise and sound localisation did not show a significant difference between type of amplification. However, the self-reported outcomes showed higher scores on 'ease of communication' and overall benefit, and significant lower scores on disability for the new hearing aids when compared to their previous hearing aids with compression amplification. Patients with Usher syndrome type IIa prefer a linear amplification over nonlinear amplification when fitted with novel hearing aids. Apart from a significantly higher logged use, no difference in speech in noise and sound localisation was observed between linear and nonlinear amplification with the currently used tests. Further research is needed to evaluate the reasons behind the preference for the linear settings. © 2016 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.
Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias
To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.
Yoshimura, Hidekane; Miyagawa, Maiko; Kumakawa, Kozo; Nishio, Shin-Ya; Usami, Shin-Ichi
Usher syndrome type 1 (USH1) is the most severe of the three USH subtypes due to its profound hearing loss, absent vestibular response and retinitis pigmentosa appearing at a prepubescent age. Six causative genes have been identified for USH1, making early diagnosis and therapy possible through DNA testing. Targeted exon sequencing of selected genes using massively parallel DNA sequencing (MPS) technology enables clinicians to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using MPS along with direct sequence analysis, we screened 227 unrelated non-syndromic deaf children and detected recessive mutations in USH1 causative genes in five patients (2.2%): three patients harbored MYO7A mutations and one each carried CDH23 or PCDH15 mutations. As indicated by an earlier genotype-phenotype correlation study of the CDH23 and PCDH15 genes, we considered the latter two patients to have USH1. Based on clinical findings, it was also highly likely that one patient with MYO7A mutations possessed USH1 due to a late onset age of walking. This first report describing the frequency (1.3-2.2%) of USH1 among non-syndromic deaf children highlights the importance of comprehensive genetic testing for early disease diagnosis.
Paul Alfaro Fernández
Full Text Available Objective: To determine the relationship between public employees’ type of work and the development of metabolic syndrome. Materials and methods: Descriptive cross-sectional observational study. The sample consisted of employees of the National Electoral Board (JNE, Lima office, who underwent their 2013 occupational medical evaluation and were assessed according to the Adult Treatment Panel III (ATP - III criteria, as amended in 2005. Data collection was obtained from the employees’ occupational medical records. Results: Three hundred twenty-two (322 employees were evaluated. The metabolic syndrome prevalence was 2.17%. The administrative sector was affected in 2.28% (p = 1.0 compared to the non-administrative sector which showed no cases. The highest prevalence of metabolic syndrome was found in 30 - 39 years old employees (3.7% (p=0.495. The study showed statistical significance in relation to male gender (p= 0.019. Conclusions: In administrative employees of the JNE, there was no relationship between the
Wimalawansa, Sunil J
The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH) 2 D 3 , especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and
Pieke-Dahl, S; Möller, C G; Kelley, P M; Astuto, L M; Cremers, C W; Gorin, M B; Kimberling, W J
Usher syndrome is a group of autosomal recessive disorders that includes retinitis pigmentosa (RP) with hearing loss. Usher syndrome type II is defined as moderate to severe hearing loss with RP. The USH2A gene at 1q41 has been isolated and characterised. In 1993, a large Usher II family affected with a mild form of RP was found to be unlinked to 1q41 markers. Subsequent linkage studies of families in our Usher series identified several type II families unlinked to USH2A and USH3 on 3q25. After a second unlinked family with many affected members and a mild retinal phenotype was discovered, a genome search using these two large families showed another Usher II locus on 5q (two point lod = 3.1 at D5S484). To date, we have identified nine unrelated 5q linked families (maximum combined multipoint lod = 5.86) as well as three Usher II families that show no significant linkage to any known Usher loci. Haplotype analysis of 5q markers indicates that the new locus is flanked by D5S428 and D5S433. Review of ophthalmological data suggests that RP symptoms are milder in 5q linked families; the RP is often not diagnosed until patients near their third decade. Enamel hypoplasia and severe, very early onset RP were observed in two of the three unlinked families; dental anomalies have not been previously described as a feature of Usher type II.
Maraj, Hemant; Mohajer, Michelle; Bhattacharjee, Deepannita
We present the case of a 31-year-old woman with Ehler-Danlos syndrome (EDS) type 2. She had a previous caesarean section and went on to have an uncomplicated vaginal birth in her last pregnancy. To our knowledge, this is the first case of a successful vaginal birth after caesarean section in a patient with EDS. EDS is a multisystem disorder involving a genetic defect in collagen and connective-tissue synthesis and structure. It is a heterogeneous group of 11 different inherited disorders. Obs...
Full Text Available Introduction. Congenital long QT syndrome type 2 (LQTS2 is a rare inherited cardiac abnormality resulting in increased risk of polymorphic ventricular tachycardia (PVT. Case Description. A 21-year-old postpartum female presented with syncopal episode after phone alarm. She was noted to have PVT on telemetry monitoring in the emergency department. EKG revealed QTc of 530. The patient’s only medication was medroxyprogesterone. She ultimately received a dual chamber pacemaker with ICD. Discussion. LQTS2 is associated with alarm sounds as a precipitating factor. Postpartum hormonal shifts as well as medroxyprogesterone have significant effect on native QTc duration.
Astuto, Lisa M.; Weston, Michael D.; Carney, Carol A.; Hoover, Denise M.; Cremers, Cor W.R.J.; Wagenaar, Mariette; Moller, Claes; Smith, Richard J.H.; Pieke-Dahl, Sandra; Greenberg, Jacquie; Ramesar, Raj; Jacobson, Samuel G.; Ayuso, Carmen; Heckenlively, John R.; Tamayo, Marta
Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A–USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were info...
Full Text Available Background: Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait. Methods: We investigated three Saudi families with CAMRQ4. Blood samples were collected from the affected patients, their parents, and healthy siblings. DNA was extracted from whole blood, and whole-exome sequencing was performed. Findings were confirmed by segregation analysis, which was performed on other family members. Results: Thus far, 17 patients have been affected by CAMRQ4. Genetic analysis of all patients, including our current patients, showed a mutation in the aminophospholipid transporter, class I, type 8A, member 2 gene ( ATP8A2 . A series of common phenotypical features have been reported in these patients, with few exceptions. Ataxia, mental retardation, and hypotonia were present in all patients, consanguinity in 90% and abnormal movements in 50%. Moreover, 40% achieved ambulation at least once in their lifetime, 40% had microcephaly, whereas 30% were mute. Magnetic resonance imaging (MRI of the brain was normal in 60% of patients. Conclusions: We described the largest cohort of patients with CAMRQ4 syndrome and identified three novel mutations. CAMRQ4 syndrome should be suspected in patients presenting with ataxia, intellectual disability, hypotonia, microcephaly, choreoathetoid movements, ophthalmoplegia, and global developmental delay, even if brain MRI appears normal.
Alsahli, Saud; Alrifai, Muhammad Talal; Al Tala, Saeed; Mutairi, Fuad Al; Alfadhel, Majid
Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait. We investigated three Saudi families with CAMRQ4. Blood samples were collected from the affected patients, their parents, and healthy siblings. DNA was extracted from whole blood, and whole-exome sequencing was performed. Findings were confirmed by segregation analysis, which was performed on other family members. Thus far, 17 patients have been affected by CAMRQ4. Genetic analysis of all patients, including our current patients, showed a mutation in the aminophospholipid transporter, class I, type 8A, member 2 gene ( ATP8A2 ). A series of common phenotypical features have been reported in these patients, with few exceptions. Ataxia, mental retardation, and hypotonia were present in all patients, consanguinity in 90% and abnormal movements in 50%. Moreover, 40% achieved ambulation at least once in their lifetime, 40% had microcephaly, whereas 30% were mute. Magnetic resonance imaging (MRI) of the brain was normal in 60% of patients. We described the largest cohort of patients with CAMRQ4 syndrome and identified three novel mutations. CAMRQ4 syndrome should be suspected in patients presenting with ataxia, intellectual disability, hypotonia, microcephaly, choreoathetoid movements, ophthalmoplegia, and global developmental delay, even if brain MRI appears normal.
Ticiana Costa Rodrigues
Full Text Available The aim of this study was to evaluate the association between the family history (FH of type 2 diabetes and metabolic syndrome (MetS in a group of non-diabetic obese female subjects. A cross-sectional study was conducted in 239 female patients with obesity, regularly attending the Internal Medicine Division’s outpatient clinic (Hospital de Clínicas de Porto Alegre, Brazil. The inclusion criteria were patients with body mass index ?30 kg/m2 and absence of type 2 diabetes. The FH was considered positive if a first degree relative had a diagnosis of diabetes. Seventy-four of 239 patients evaluated (30% had a positive FH for type 2 diabetes. Patients with positive FH had higher waist/hip ratio and MetS more often than patients with negative FH. FH of type 2 diabetes was associated with MetS in this sample of non-diabetic obese female patients. Waist/hip ratio and fasting plasma glucose, markers of insulin resistance, were also associated with FH of type 2 diabetes. The simple question: “Do you have a FH of type 2 diabetes?” may help to identify the obese patients that should be better evaluated and intensively treated with the objective of preventing type 2 diabetes.
Chen, Kaitian; Zong, Ling; Liu, Min; Zhan, Yuan; Wu, Xuan; Zou, Wenting; Jiang, Hongyan
Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Full Text Available The influence of obesity on cardiometabolic health in the general population has been widely studied, but few studies are dealing with the problem of obesity in children and adolescents with type 1 diabetes. Aim: The aim of this study was to determine the presence of overweight, and obese persons with metabolic syndrome in children and adolescents with type 1 diabetes and to determine the conection of nutritional status with other risk factors for cardiovascular disease, such as dyslipidemia, glycoregulation, high blood pressure , insulin dose, age, illness, length of illness. Methods: The study included 197 children and adolescents with type 1 diabetes mellitus (103 females, 94 males. The average age of respondents was 12,71 years. Data on body weight, height, BMI was calculated according to the formula kg/m2. Standard laboratory procedures were determined, total cholesterol, LDL and HDL cholesterol, AST, GHbA1c, data on a daily dose of insulin, and type of insulin therapy, age at which the disease began, duration of disease, the possible existence of microvascular complications (microalbuminuria, retinopathy, neuropathy and hypertension were obtained. Results: There were 77,2% patients had normal weight, 14,2% were overweight, 3,4% were obese and 5,2% nutritional had metabolic syndrome. We found statistically significant conection between nutritional impairment and total cholesterol, tryglycerides, hypertension, length of disease and daily insuline dose. Conclusion: Due to the fact that people with type 1 diabetes are at high risk for the development of vascular complications, prevention, early detection and treatment of nutritional impairment as well as other cardiometabolic risk factors are imperative.
Delattre, Marie; Balestra, Fernando R.; Blanchoud, Simon; Finger, Susanne; Knott, Graham; Müller-Reichert, Thomas; Gönczy, Pierre
Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sperm cells, where such integrity is particularly critical. We identified C. elegans sas-1 in a genetic screen as a locus required for bipolar spindle assembly in the early embryo. Our analysis reveals that sperm-derived sas-1 mutant centrioles lose their integrity shortly after fertilization, and that a related defect occurs when maternal sas-1 function is lacking. We establish that sas-1 encodes a C2 domain containing protein that localizes to centrioles in C. elegans, and which can bind and stabilize microtubules when expressed in human cells. Moreover, we uncover that SAS-1 is related to C2CD3, a protein required for complete centriole formation in human cells and affected in a type of oral-facial-digital (OFD) syndrome. PMID:25412110
Lukas von Tobel
Full Text Available Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sperm cells, where such integrity is particularly critical. We identified C. elegans sas-1 in a genetic screen as a locus required for bipolar spindle assembly in the early embryo. Our analysis reveals that sperm-derived sas-1 mutant centrioles lose their integrity shortly after fertilization, and that a related defect occurs when maternal sas-1 function is lacking. We establish that sas-1 encodes a C2 domain containing protein that localizes to centrioles in C. elegans, and which can bind and stabilize microtubules when expressed in human cells. Moreover, we uncover that SAS-1 is related to C2CD3, a protein required for complete centriole formation in human cells and affected in a type of oral-facial-digital (OFD syndrome.
Shukla, Garima; Kaul, Bhavna; Gupta, Anupama; Goyal, Vinay; Behari, Madhuri
Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made. This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations. Copyright 2015, NMJI.
Issa, Sarah; Bondurand, Nadege; Faubert, Emmanuelle; Poisson, Sylvain; Lecerf, Laure; Nitschke, Patrick; Deggouj, Naima; Loundon, Natalie; Jonard, Laurence; David, Albert; Sznajer, Yves; Blanchet, Patricia; Marlin, Sandrine; Pingault, Veronique
Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss and pigmentation anomalies. The clinical definition of four WS types is based on additional features due to defects in structures mostly arising from the neural crest, with type I and type II being the most frequent. While type I is tightly associated to PAX3 mutations, WS type II (WS2) remains partly enigmatic with mutations in known genes (MITF, SOX10) accounting for only 30% of the cases. We performed exome sequencing in a WS2 index case and identified a heterozygous missense variation in EDNRB. Interestingly, homozygous (and very rare heterozygous) EDNRB mutations are already described in type IV WS (i.e., in association with Hirschsprung disease [HD]) and heterozygous mutations in isolated HD. Screening of a WS2 cohort led to the identification of an overall of six heterozygous EDNRB variations. Clinical phenotypes, pedigrees and molecular segregation investigations unraveled a dominant mode of inheritance with incomplete penetrance. In parallel, cellular and functional studies showed that each of the mutations impairs the subcellular localization of the receptor or induces a defective downstream signaling pathway. Based on our results, we now estimate EDNRB mutations to be responsible for 5%-6% of WS2. © 2017 Wiley Periodicals, Inc.
Sun, Lianhua; Li, Xiaohua; Shi, Jun; Pang, Xiuhong; Hu, Yechen; Wang, Xiaowen; Wu, Hao; Yang, Tao
Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detected PAX3 mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified with SOX10 and MITF mutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available, de novo mutations were frequently seen for SOX10 mutations (7/8) but not for MITF mutations (0/5, P = 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands with MITF mutations (7/10) but not in those with SOX10 mutations (0/13, P = 4.9 × 10 -4 ). Our results showed that mutations in SOX10 and MITF are two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the high de novo rate of the SOX10 mutations and the excessive freckle phenotype exclusively associated with the MITF mutations.
Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing
The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research.
Zong, Ling; Chen, Kaitian; Wu, Xuan; Liu, Min; Jiang, Hongyan
Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Acute kidney injury (AKI is a common complication of liver cirrhosis and mainly manifests as a rapidly elevated serum creatinine level, a reduced glomerular filtration rate, and oliguria or anuria. Type 1 hepatorenal syndrome (HRS-1 is a special type of AKI, and patients with untreated HRS-1 have an extremely high risk of death. Early diagnosis and treatment are of great importance. This paper summarizes the latest diagnostic criteria for hepatorenal syndrome (HRS type of AKI and research advances in the treatment of HRS-1.
Hemi chorea-hemiballism syndrome, which is most commonly related to non-ketotic hyperglycemia, is a rare type of chorea. Here, we present an unusual case of Hemi chorea-hemiballism syndrome who was not a known case of diabetes. This case highlights the importance of recognising underlying non-ketotic hyperglycemia, as control of hyperglycemia is helpful in the quick relief of symptoms.
Zheng, Lei; Yan, Yousheng; Chen, Xue; Zhang, Chuan; Zhang, Qinghua; Feng, Xuan; Hao, Shen
OBJECTIVE To detect potential mutation of SOX10 gene in a pedigree affected with Warrdenburg syndrome type II. METHODS Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Exons and flanking sequences of MITF, PAX3, SOX10, SNAI2, END3 and ENDRB genes were analyzed by chip capturing and high throughput sequencing. Suspected mutations were verified with Sanger sequencing. RESULTS A c.127C>T (p.R43X) mutation of the SOX10 gene was detected in the proband, for which both parents showed a wild-type genotype. CONCLUSION The c.127C>T (p.R43X) mutation of SOX10 gene probably underlies the ocular symptoms and hearing loss of the proband.
Rams, Anna; Żółciński, Marek; Zastrzeżyńska, Weronika; Polański, Stanisław; Serafin, Agnieszka; Wilańska, Joanna; Musiał, Jacek; Bazan-Socha, Stanisława
Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.
Lakshmipriya, Nagarajan; Gayathri, Rajagopal; Praseena, Kallingal; Vijayalakshmi, Parthasarathy; Geetha, Gunasekaran; Sudha, Vasudevan; Krishnaswamy, Kamala; Anjana, Ranjit Mohan; Henry, Jeyakumar; Mohan, Viswanathan
There is little data on the type of vegetable oil used and the prevalence of metabolic syndrome (MS) in Asian Indians. Food frequency questionnaire was used to document the type of cooking oil in 1875 adults in Chennai city. MS was assessed by new harmonizing criteria. The prevalence of MS was higher among sunflower oil users (30.7%) than palmolein (23.2%) and traditional oil (17.1%, p < 0.001) users. The higher prevalence of MS in sunflower oil group persisted even when stratified according to body mass index, except in obese groups. The risk of MS was further compounded by quantity of refined cereals consumed. Higher LA%E and linoleic acid/alpha-linolenic acid ratio in sunflower oil probably contributes to increased risk of MS.
Oleksiewicz, M.B.; Bøtner, Anette; Madsen, K.G.
Following the recent use of a live vaccine against porcine reproductive and respiratory syndrome virus (PRRSV) in Denmark, both American (vaccine) and European-type PRRSV now coexist in Danish herds. This situation highlighted a requirement for supplementary tests for precise virus-typing. As a r...
Tamagawa, Eri; Inaba, Hidefumi; Ota, Takayuki; Ariyasu, Hiroyuki; Kawashima, Hiromichi; Wakasaki, Hisao; Furuta, Hiroto; Nishi, Masahiro; Nakao, Taisei; Kaito, Hiroshi; Iijima, Kazumoto; Nakanishi, Koichi; Yoshikawa, Norishige; Akamizu, Takashi
Bartter syndrome (BS) is a disorder with normotensive hypokalemic alkalosis and hyperreninemic hyperaldosteronemia. BS affects infants or early childhood. Patients with BS type 3 harbor mutation in CLCNKB, Cl channel Kb. Gitelman syndrome (GS) is a disorder in childhood, with mutation in SLC12A3. Isolated adrenocorticotropin deficiency (IAD) causes secondary adrenal insufficiency. Neither elderly cases, nor cases with IAD were previously reported in BS. A 72-year-old man was admitted with acute adrenal crisis. He had been treated for IAD for 19 years. He had no trouble during perinatal period, delivery, and growth. After the recovery from adrenal crisis, laboratory tests revealed hypokalemia; 3.0 mEq/L (normal: 3.5-4.5), impaired renal function: eGFR; 37.6 mL/min/1.73 m2, normomagnesemia; 2.1 mg/dL (1.7-2.3), hyperreninemia; 59.4 ng/mL/h (0.2-2.7), hyperaldosteronemia; 23.5 ng/dL (3.0-15.9), and normal urinary ratio of calcium/creatinine. In diuretic tests, he showed a fine response to furosemide, and a mild response to thiazide. In genetic tests, no mutation of SLC12A3 was found and homozygous mutation: c.1830 G > A in CLCNKB was shown. Thus he was diagnosed as BS type 3. Current case presented with unusual features as BS type 3, 1) his late and mild clinical manifestation suggested GS rather than BS, 2) laboratory data and diuretics tests did not show typical features as BS, and 3) IAD and chronic renal failure altered electrolyte metabolism. In conclusion, current case implies that BS type 3 should be considered even in elderly cases with normotensive hypokalemia, and highlights importance of endocrinological and genetic examinations.
Full Text Available Abstract Ehlers Danlos syndrome (EDS athrocalasia type (type VII, is characterized by joint hypermobility, skin hyperextensibility and tissue fragility. No heart involvement has been reported. Two forms have been described: type VII A and VII B. The abnormally processed collagen α2(I and the skipping of the exon 6 in COL1A2 gene are typically detected in EDS type VII B. We describe a seven-year old female, with a phenotype consistent with EDS type VII B and a diagnosis further confirmed by biochemical and molecular analyses. Cardiac ultrasound showed normal data in the first year of life. When she was 5 years old, the patient developed mitral valve regurgitation, and aortic and tricuspidal insufficiency at 7 years of age. To our knowledge, this is the first report of cardiac valvular involvement in EDS VII B. This feature probably has been underreported for the limited follow-up of the patients. Echocardiography might be warranted in the clinical assessment of EDS VII patients.
Objective: To investigate and evaluate PTA and stenting for various types of Budd-Chiari syndrome (BCS). Methods: 89 patients with BCS were diagnosed and treated during 7 years. The interventional procedures included: Percutaneous balloon dilatation (PBD) of inferior vena cava (IVC), PBD and stent placement for IVC, hepatic vein angioplasty via trans jugular vein, hepatic vein angioplasty via transhepatic and trans jugular approach, accessory hepatic vein angioplasty, percutaneous dual balloon dilatation for IVC and hepatic vein, and percutanous dual stent placement for IVC and hepatic vein. Results: The achievement ratio of PTA and stent placement was 96% and the mortality was 0%. The serious complication of PTA and stent placement of BCS was penetration into the pericardium, endovascular stent migration into right atrium. Conclusion: 1. PTA is a reliable procedures in treating type I a, II and III BCS, and TIPPS is useful for type I b BCS. But PTA and stenting is necessary for patients with type IV BCS. 2. Thrombolysis is needed for patients with type III, IV BCS. 3. Guiding of Color Doppler Ultrasound can improve the success of percutanous hepatic vein and reduce complications. (authors)
Savonitto, Stefano; Morici, Nuccia; Nozza, Anna; Cosentino, Francesco; Perrone Filardi, Pasquale; Murena, Ernesto; Morocutti, Giorgio; Ferri, Marco; Cavallini, Claudio; Eijkemans, Marinus Jc; Stähli, Barbara E; Schrieks, Ilse C; Toyama, Tadashi; Lambers Heerspink, H J; Malmberg, Klas; Schwartz, Gregory G; Lincoff, A Michael; Ryden, Lars; Tardif, Jean Claude; Grobbee, Diederick E
To define the predictors of long-term mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome. A total of 7226 patients from a randomized trial, testing the effect on cardiovascular outcomes of the dual peroxisome proliferator-activated receptor agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2 years. The independent mortality predictors were defined using Cox regression analysis. The predictive information provided by each variable was calculated as percent of total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular death contributing for 73% of mortality. The mortality prediction model included N-terminal proB-type natriuretic peptide (adjusted hazard ratio = 1.68; 95% confidence interval = 1.51-1.88; 27% of prediction), lack of coronary revascularization (hazard ratio = 2.28; 95% confidence interval = 1.77-2.93; 18% of prediction), age (hazard ratio = 1.04; 95% confidence interval = 1.02-1.05; 15% of prediction), heart rate (hazard ratio = 1.02; 95% confidence interval = 1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio = 1.11; 95% confidence interval = 1.03-1.19; 8% of prediction), haemoglobin (hazard ratio = 1.01; 95% confidence interval = 1.00-1.02; 8% of prediction), prior coronary artery bypass (hazard ratio = 1.61; 95% confidence interval = 1.11-2.32; 7% of prediction) and prior myocardial infarction (hazard ratio = 1.40; 95% confidence interval = 1.05-1.87; 6% of prediction). In patients with type 2 diabetes mellitus and recent acute coronary syndrome, mortality prediction is largely dominated by markers of cardiac, rather than metabolic, dysfunction.
Full Text Available Abstract Background Loeys-Dietz syndrome (LDS is a rare autosomal dominant disorder showing the involvement of cutaneous, cardiovascular, craniofacial, and skeletal systems. In particular, LDS patients show arterial tortuosity with widespread vascular aneurysm and dissection, and have a high risk of aortic dissection or rupture at an early age and at aortic diameters that ordinarily are not predictive of these events. Recently, LDS has been subdivided in LDS type I (LDSI and type II (LDSII on the basis of the presence or the absence of cranio-facial involvement, respectively. Furthermore, LDSII patients display at least two of the major signs of vascular Ehlers-Danlos syndrome. LDS is caused by mutations in the transforming growth factor (TGF beta-receptor I (TGFBR1 and II (TGFBR2 genes. The aim of this study was the clinical and molecular characterization of two LDS patients. Methods The exons and intronic flanking regions of TGFBR1 and TGFBR2 genes were amplified and sequence analysis was performed. Results Patient 1 was a boy showing dysmorphic signs, blue sclerae, high-arched palate, bifid uvula; skeletal system involvement, joint hypermobility, velvety and translucent skin, aortic root dilatation, tortuosity and elongation of the carotid arteries. These signs are consistent with an LDSI phenotype. The sequencing analysis disclosed the novel TGFBR1 p.Asp351Gly de novo mutation falling in the kinase domain of the receptor. Patient 2 was an adult woman showing ascending aorta aneurysm, with vascular complications following surgery intervention. Velvety and translucent skin, venous varicosities and wrist dislocation were present. These signs are consistent with an LDSII phenotype. In this patient and in her daughter, TGFBR2 genotyping disclosed in the kinase domain of the protein the novel p.Ile510Ser missense mutation. Conclusion We report two novel mutations in the TGFBR1 and TGFBR2 genes in two patients affected with LDS and showing marked
Ben-Rebeh, Imen; Grati, Mhamed; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber
Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient's early childhood is of utmost importance, allowing better educational and therapeutic management.
Piane, Maria; Della Monica, Matteo; Piatelli, Gianluca; Lulli, Patrizia; Lonardo, Fortunato; Chessa, Luciana; Scarano, Gioacchino
We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome. At age 3 years, he became paralyzed due to a cerebrovascular malformation. Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the patient's lymphoblastoid cell line lysate showed the absence of the protein pericentrin. Subsequent molecular analysis identified a novel homozygous single base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in the development of cerebral vessels is suggested. Copyright 2009 Wiley-Liss, Inc.
Chen, H S; Liao, X B; Liu, Y L; He, C F; Zhang, H; Jiang, L; Feng, Y; Mei, L Y
Objective: To investigate the clinical chacteration and molecular pathology of Waardenburg syndrome type 2 in seven families, and provide genetic diagnosis and hereditary counseling for family members. Method: Clinical data of seven families with WS2（14 patients）were collected. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of microphthalmia associated transcription factor (MITF), sex-determining region Y-box 10(SOX10), snail family zinc finger 2 (SNAI2) and endothelin receptor type B（EDNRB）were analyzed by polymerase chain reaction and DNA sequencing. Then the raw data was analyzed. Result: The most common manifestations of WS2 are sensorineural hearing loss(10/14,71.4%), freckle(7/14, 50.0%)，heterochromia iridis(6/14, 42.9%) and premature greying(5/14,35.7%). All the deafness phenotype is congenital, bilateral profound sensorineural hearing loss. Freckles phenotype is different from cutaneous pigment abnormalities of WS in Westerners. The heterozygous mutation, c.328C>T in exon 3 of the MITF gene was detected in the proband and all patients of pedigree 2. However, no pathological mutation of the relevant genes (SOX10,SNAI2 and EDNRB) was detected in other pedigrees. Conclusion: There are obvious variations in clinical features of WS, while freckles may be a special subtype of cutaneous pigment disturbances. The MITF gene mutation, R110X,is therefore considered the disease causing mutation in pedigree WS02.However, there are novel disease causing genes or copy number variations in Waardenburg syndrome type 2, which require further research. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.
Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco
Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. © 2015 Wiley Periodicals, Inc.
Trabelsi, Mediha; Nouira, Malek; Maazoul, Faouzi; Kraoua, Lilia; Meddeb, Rim; Ouertani, Ines; Chelly, Imen; Benoit, Valérie; Besbes, Ghazi; Mrad, Ridha
Waardenburg syndrome (WS) is an auditory-pigmentary disease characterized by a clinical and genetic variability. WS is classified into four types depending on the presence or absence of additional symptoms: WS1, WS2, WS3 and WS4. Type 1 and 3 are mostly caused by PAX3 mutations, while type 2 and type 4 are genetically heterogeneous. The aims of this study are to confirm the diagnostic of WS1 by the sequencing of PAX3 gene and to evaluate the genotype phenotype correlation. A clinical classification was established for 14 patients WS, as proposed by the Waardenburg Consortium, and noted a predominance of type 1 and type 2 with 6 patients WS1, 7 patients WS2 and 1 patient WS3. A significant inter and intra-familial clinical heterogeneity was also observed. A sequencing of PAX3 gene in the 6 patients WS1 confirmed the diagnosis in 4 of them by revealing three novel mutations that modify two functional domains of the protein: the c.942delC; the c.933_936dupTTAC and the c.164delTCCGCCACA. These three variations are most likely responsible for the phenotype, however their pathogenic effects need to be confirmed by functional studies. The MLPA analysis of the 2 patients who were sequence negative for PAX3 gene revealed, in one of them, a heterozygous deletion of exons 5 to 9 confirming the WS1 diagnosis. Both clinical and molecular approaches led to the conclusion that there is a lack of genotype-phenotype correlation in WS1, an element that must be taken into account in genetic counseling. The absence of PAX3 mutation in one patient WS1 highlights the fact that the clinical classification is sometimes insufficient to distinguish WS1 from other types WS hence the interest of sequencing the other WS genes in this patient. Copyright © 2017 Elsevier B.V. All rights reserved.
Sankila, E M; Pakarinen, L; Kääriäinen, H; Aittomäki, K; Karjalainen, S; Sistonen, P; de la Chapelle, A
Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)
Roncalés-Samanes, P; de Arriba Muñoz, A; Lou Francés, G M; Ferrer Lozano, M; Justa Roldán, M L; Labarta Aizpun, J I
Polyglandular autoimmune syndromes are rare diseases based on autoimmune mechanisms in which endocrine and non-endocrine disorders coexist. In type 1 the characteristic manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. A case is presented of a patient with typical clinical sequence, along with other changes, and in whom a mutation in homozygosis, C322fsX372, was detected after performing a molecular analysis of autoimmunity regulator gene (AIRE). Inheritance is autosomal recessive, associated with mutations in the AIRE gene, which encodes a protein involved in autoimmunity and immunodeficiency. For diagnosis, At least two of the three major clinical manifestations are required for a diagnosis. However, only one of them is necessary in the study of relatives of affected patients. These syndromes must be diagnosed early, given their high morbidity and mortality. Every manifestation needs to be treated, in order to maintain the quality of life. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Wang, Huanhuan; Tang, Lifang; Zhang, Jingmin; Hu, Qin; Chen, Yingwei; Xiao, Bing
To determine the genetic cause for a patient featuring decreased pigmentation of the skin and iris, hearing loss and multiple congenital anomalies. Routine chromosomal banding was performed to analyze the karyotype of the patient and his parents. Single nucleotide polymorphism array (SNP array) was employed to identify cryptic chromosome aberrations, and quantitative real-time PCR was used to confirm the results. Karyotype analysis has revealed no obvious anomaly for the patient and his parents. SNP array analysis of the patient has demonstrated a 3.9 Mb deletion encompassing 3p13p14.1, which caused loss of entire MITF gene. The deletion was confirmed by quantitative real-time PCR. Clinical features of the patient have included severe bilateral hearing loss, decreased pigmentation of the skin and iris and multiple congenital anomalies. The patient, carrying a 3p13p14.1 deletion, has features of Tietz syndrome/Waardenburg syndrome type IIa. This case may provide additional data for the study of genotype-phenotype correlation of this disease.
Xiao, Yun; Luo, Jianfen; Zhang, Fengguo; Li, Jianfeng; Han, Yuechen; Zhang, Daogong; Wang, Mingming; Ma, Yalin; Xu, Lei; Bai, Xiaohui; Wang, Haibo
The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1. Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1). WS1 was diagnosed in a 4-year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis. A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic.
Alice Rachel Bandeira de Araújo
Full Text Available The autoimmune polyendocrinopathy syndrome type 1 (APS-1, also known as candidiasis ectodermal-autoimmune polyendocrinopathy-dystrophy (APECED, it is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE. Therefore, it is immunologically characterized by cell attack and / or antibodymediated generating the destruction of target organs. Furthermore, it is characterized by the pathognomonic triad chronic candidiasis, hypoparathyroidism and Addison's disease with many other endocrine and non-endocrine events. Soon, the diagnosis is made based on the presence of two of the three classic features and treatment aims to control the numerous deficiencies that patients may present. This literature review was aimed at understanding the involvement of AIRE gene in relation to immunological aspects present and, consequently, clinical manifestations of this disease. Thus, evidence of the need to broaden the discussion about this disease, in order to improve the quality of life of patients by early diagnosis and treatment and are in accordance with the clinical manifestations of each patient. Thereby, qualitative research involved scientific articles from electronic journals LILACS (Latin American and Caribbean, SCIELO (Scientific Electronic Library Online and NCBI (National Center for Biotechnology Information, between the years 2009 and 2016. Pursuant to, there is the relevance of this review, it is noted that, although the authors converge on views on this syndrome, there are still many unclear matters with regard to the mechanisms of the disease. This highlights the need to promote more discussion on this topic.
Chen, Jing; Yang, Shu-Zhi; Liu, Jun; Han, Bing; Wang, Guo-Jian; Zhang, Xin; Kang, Dong-Yang; Dai, Pu; Young, Wie-Yen; Yuan, Hui-Jun
Warrgenburg syndrome type 2 (WS2) is the most common autosomal dominantly-inherited syndrome with hearing loss. MITF (microphthalmia associated transcription factor)is a basic-helix-loop-helix-luecine zipper (bHLHZip) factor which regulates expression of tyrosinase, and is involved in melanocyte differentiation. Mutations in MITF associated with WS2 have been identified in some but not all affected families. Here, we report a three-generation Chinese family with a point mutation in the MITF gene causing WS2. The proband exhibits congenital severe sensorineural hearing loss, heterochromia iridis and facial freckles. One of family members manifests sensorineural deafness, and the other patients show premature greying or/and freckles. This mutation, heterozygous deletion c.639delA, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking normal interaction with its target DNA motif. This mutation is a novel mutation and the third case identified in exon 7 of MITF in WS2. Though there is only one base pair distance between this novel mutation and the other two documented cases and similar amino acids change, significant difference is seen in clinical phenotype, which suggests genetic background may play an important role.
Alin Laurentiu Tatu
Full Text Available The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS. Abnormalities of T cell-mediated immunity and humoral immunity have been described previously in the literature. Aims of work were to investigate the 22 years old patient with lupus erythematosus for three years and autoimune thyroiditis for one year, regardind other possible autoimmune conditions and to establish a treatment to control the diseases. The clinical exam revealed some circular hairless patches on the beard appeared about three months ago and white depigmented disseminated areas started one month ago and the laboratory investigations were performed. The modified laboratory findings were total IgE 530 UI/mL, Anti-SSA (anti-RO antibodies> 200 IU/mL, SSB negative, Antinuclear antibodies (ANA positive and fine speckled, Lupus anticoagulant testing positive, Anti-thyroid peroxidase antibodies 951 UI/ml, TSH 4,7 µUI/mL. The diagnosis of multiple autoimmune syndrome(MAS type 3 including Lupus erythematosus, autoimune Thyroiditis, Alopecia Areata and Vitiligo was established. Endocrine autoimmunities are associated with autoantibodies that react to specific antigens, whereas patients with collagen diseases synthesize immunoglobulins that recognize nonorgan-specific cellular targets, such as nucleoproteins and nucleic acids. Cellular autoimmunity is important in the pathogenesis MAS. The existence of one autoimmune disorder helps lead to the discovery of other autoimmune conditions.
Olczak-Kowalczyk, Dorota; Pyrżak, Beata; Dąbkowska, Maria; Pańczyk-Tomaszewska, Małgorzata; Miszkurka, Grażyna; Rogozińska, Izabela; Swoboda-Kopeć, Ewa; Gozdowski, Dariusz; Kalińska, Angelika; Piróg, Anna; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria
Diabetes and Nephrotic syndrome (NS) promote plaque-related gingivitis and yeast-like fungal infections. The study assesses the impact of Candida spp. and general disease- or treatment-related factors on plaque-related gingivitis severity in children and adolescents with Nephrotic syndrome /diabetes. Body mass index (BMI), BMI standard deviation score, and oral cavity (Plaque Index--PLI, Gingival Index--GI, mucosa status, presence and Candida enzymatic activity) were assessed in 96 patients (32 with NS: 30- immunosuppressive treatment, 35--type 1 diabetes, and 29 generally healthy), aged; 3-18 years. Laboratory included cholesterol and triglyceride measurements; in diabetic subjects- glycated haemoglobin, in NS: total protein, albumin, creatinine, haemoglobin, haematocrit, white cell count, urinary protein excretion. Medical records supplied information on disease duration and treatment. A statistical analysis was performed; Kendall Tau coefficient, chi-square test, t-test, and multiple regression analysis ( P Gingivitis occurred more frequently in patients with NS/diabetes. Gingivitis severity was correlated with PLI, age, and yeast enzyme activity in NS--to with immunosuppressive treatment with >1 drug, drug doses, treatment duration, lipid disorders, and BMI; in diabetes, with blood glucose and glycated haemoglobin >8%. Poor hygiene control is the main cause of gingivitis. Gingivitis severity is most likely related to age, lipid disorders and increase in body mass. Candida spp., in uncompensated diabetes and in those using immunosuppressive treatment, might intensify plaque-related gingivitis.
Guo, Can-Jie; Leung, Patrick S C; Zhang, Weici; Ma, Xiong; Gershwin, M Eric
Autoimmune Polyglandular Syndrome type 1 (APS-1) is a subtype of the autoimmune polyendocrine syndrome characterized by the simultaneous or sequential dysfunction of multiple endocrine or non-endocrine glands. A clinical diagnosis of APS-1 is typically based on the presence of at least two of three following criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. The first identified causative mutated gene for APS-1 is autoimmune regulator (AIRE) encoding a critical transcription factor, which is primarily expressed in the medullary thymic epithelial cells (mTECs) for generating central immune tolerance. A wide range of chronic, debilitating complications, with no obvious correlation with genetics, makes a diagnosis of APS-1 challenging early in the disease course. Managing APS-1 is difficult due to its complexity, especially the intricate relationships within manifestations and genetic mutations. The past decades have witnessed dramatic progress in elucidating the function of AIRE and conducting large-scale cohort studies in APS-1. However, no clear evidence-based guidelines have been established in APS-1. In this review, we provide a detailed critical overview of the study history, epidemiology, clinical features, and related mechanisms of autoimmunity in APS-1, as well as currently available therapies for this autoimmune disorder. Copyright © 2017 Elsevier B.V. All rights reserved.
Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder that causes ... and vision. There are three types of Usher syndrome: People with type I are deaf from birth ...
Reiners, Jan; van Wijk, Erwin; Märker, Tina; Zimmermann, Ulrike; Jürgens, Karin; te Brinke, Heleen; Overlack, Nora; Roepman, Ronald; Knipper, Marlies; Kremer, Hannie; Wolfrum, Uwe
Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. USH is clinically and genetically heterogeneous with at least 11 chromosomal loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the different USH types exhibit almost the same phenotype in human, the identified USH genes encode for proteins which belong to very different protein classes and families. We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network. Here, we investigated the relationship between the USH2 molecules and this USH1-protein network. We show a molecular interaction between the scaffold protein harmonin (USH1C) and the USH2A protein, VLGR1 (USH2C) and the candidate for USH2B, NBC3. We pinpoint these interactions to interactions between the PDZ1 domain of harmonin and the PDZ-binding motifs at the C-termini of the USH2 proteins and NBC3. We demonstrate that USH2A, VLGR1 and NBC3 are co-expressed with the USH1-protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells. In hair cells, these USH proteins are also localized in the signal uptaking stereocilia. Our data indicate that the USH2 proteins and NBC3 are further partners in the supramolecular USH-protein network in the retina and inner ear which shed new light on the function of USH2 proteins and the entire USH-protein network. These findings provide first evidence for a molecular linkage between the pathophysiology in USH1 and USH2. The organization of USH molecules in a mutual 'interactome' related to the disease can explain the common phenotype in USH.
Maria Betânia Pereira Toralles
Full Text Available The action of glucocorticoids is modulated by isoenzymes 11?-hidroxiesteróide desidrogenases (11?-HSD type 1 and 2. The knowledge concerning these isoenzymes contribute to the understanding of the regulatory mechanisms involved in several disease processes of the Cushing’s syndrome, such as obesity, osteoporosis and hypertension. With the aim at describing the action of isoenzymes 11?-HSD type 1 and 2 in the Cushing’s syndrome, a literature review was done from 1990 - 2006 using the Medline data base, searching for the following key-words: Cushing’s syndrome, glucocorticoids, 11?-hydroxysteroid dehydrogenase, hypertension, osteoporosis and obesity. Review studies, meta-analysis and original articles were selected and chosen on the basis of methodological aspects and relevance. The exact mechanism by which cortisol increases blood pressure is not completely understood, but it involves, among others factors, changes in the sodium homeostasis. The conversion of cortisone to cortisol through expression of 11?-HSD1 induces the differentiation of preadipoctyes to mature adipoctyes and such patients develop an increase in visceral fat. The prevalence of osteoporosis in adult patients with Cushing’s syndrome is approximately 50% and glucocorticoids play a strong effect on the bone and calcium metabolism. The isoenzymes 11?-HSD1 and 11?-HSD2 have an important function in these several pathophysiology processes; however the isoenzymes action in the pathophysiology of the Cushing’s syndrome need to be more investigated.
Cruz, António José; Castro, Alexandra
A 32-year-old woman with no significant medical history was sent to our consultation due to hypokalaemia (syndrome (GS) came negative. CLCNKB gene mutation analysis present in both GS and Bartter (BS) type 3 syndromes was positive. The patient is now being treated with potassium and magnesium oral supplements, ramipril and spironolactone with stable near-normal potassium and magnesium levels. This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3.
Full Text Available Background Subjects with metabolic syndrome (MetS have a greater risk for acquiring type 2 diabetes mellitus (type 2 DM. The MetS criteria usually used are those of the National Cholesterol Education Program Expert Panel (NCEP and Adult Treatment Panel III (ATP III and of the International Diabetes Federation (IDF. This study aimed to evaluate the modified NCEP-ATP III and IDF criteria as predictor of type 2 DM among subjects with MetS. Methods A cohort study was conducted among 4240 subjects with MetS. MetS was determined according to the modified NCEP-ATP III and IDF criteria. The study followed up 3324 non-diabetic subjects of the cohort study of non-communicable disease (NCD risk factors (NCD study during a 2-year period. Type 2 DM was determined from the diagnosis by health personnel or from fasting blood glucose of ≥126 mg/dL or blood glucose of ≥200 mg/dL, 2 hours after 75g glucose loading. Results The MetS prevalence based on modified NCEP ATP III and IDF criteria in non-DM subjects was 17.1% and 15.6%, respectively. The risk for DM in subjects with MetS using modified NCEP ATP III and IDF criteria was 4.7 (CI 95%: 3.4-6.5 and 4.1 (CI 95%: 3.0-5.7, respectively. Conclusions Both MetS criteria can be used as predictors of the occurrence of DM type 2, but the modified NCEP-ATP III is more properly applied than the IDF criteria in subjects with MetS. Screening programs and routine monitoring of MetS components are required for early detection of type 2 DM.
Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhu, Ganghua; Hu, Peng; Wu, Weijing
To explore the molecular etiology of two pedigrees affected with type II Waardenburg syndrome (WS2) and to provide genetic diagnosis and counseling. Blood samples were collected from the proband and his family members. Following extraction of genomic DNA, the coding sequences of PAX3, MITF, SOX10 and SNAI2 genes were amplified with PCR and subjected to DNA sequencing to detect potential mutations. A heterozygous deletional mutation c.649_651delAGA in exon 7 of the MITF gene has been identified in all patients from the first family, while no mutation was found in the other WS2 related genes including PAX3, MITF, SOX10 and SNAI2. The heterozygous deletion mutation c.649_651delAGA in exon 7 of the MITF gene probably underlies the disease in the first family. It is expected that other genes may also underlie WS2.
Jean Ann Maguire
Full Text Available Hermansky–Pudlak syndrome type 2 (HPS2 is a rare autosomal recessive disorder resulting from functional mutations in the adaptor-related protein complex 3, beta 1 subunit (AP3B1 gene. This gene plays a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. Here we describe the generation of an HPS2 iPS cell line (CHOPHPS2 using a Cre-excisable polycistronic STEMCCA lentivirus. This line was derived from human fibroblasts isolated from a patient carrying two mutations in the AP3B1 gene. The patient presented with severe neutropenia, ocular albinism, interstitial pulmonary fibrosis, hemorrhagic diathesis, and an absence of platelet-dense granules.
Anwar, Safa; Shikalgar, Nigar
Polycystic ovary syndrome (PCOS) is recognized as one of the most common endocrinopathies in women of reproductive age, associated with metabolic sequelae which includes increased risk factors for impaired glucose tolerance (IGT), type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). The adverse effects of DM2 affects a woman throughout her lifespan. Health care expenditure of DM2 highlights the need for prevention through appropriate screening, diagnosis and intervention. Lifestyle modification (LSM) programs that include diet and/or physical activity are suggested for patients characterized as prediabetic to delay the onset of adult DM2. Diet (i.e. low carbohydrate), combination of aerobic and resistance exercise with high intensity interval training (HIT) 150 to 175min/week with resistance exercise 2 to 3days/week and weight loss may be valuable supporters in the fight against IR, IGT and DM2 associated with PCOS. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Selicorni, Angelo; Guerneri, Silvana; Ratti, Antonia; Pizzuti, Antonio
An Italian family in which Waardenburg syndrome type II (WS2) segregates together with a der(8) chromosome from a (4p;8p) balanced translocation was studied. Cytogenetic analysis by painting and subtelomeric probe hybridization positioned the chromosome 8 breakpoint at p22-pter. Fluorescence in situ hybridization analysis with yeast artificial chromosomes from a contig spanning the 8p21-pter region refined the breakpoint in an interval of less than 170 kb between markers WI-3823 and D8S1819. The only cloned gene for WS2 is that for microphtalmia (MITF) on chromosome 3p. In this family, MITF mutations were excluded by sequencing the whole coding region. The 8p23 region may represent a third locus for WS2 (WS2C).
Yoshimura, Hidekane; Oshikawa, Chie; Nakayama, Jun; Moteki, Hideaki; Usami, Shin-Ichi
This study examines the CLRN1 gene mutation analysis in Japanese patients who were diagnosed with Usher syndrome type 3 (USH3) on the basis of clinical findings. Genetic analysis using massively parallel DNA sequencing (MPS) was conducted to search for 9 causative USH genes in 2 USH3 patients. We identified the novel pathogenic mutation in the CLRN1 gene in 2 patients. The missense mutation was confirmed by functional prediction software and segregation analysis. Both patients were diagnosed as having USH3 caused by the CLRN1 gene mutation. This is the first report of USH3 with a CLRN1 gene mutation in Asian populations. Validating the presence of clinical findings is imperative for properly differentiating among USH subtypes. In addition, mutation screening using MPS enables the identification of causative mutations in USH. The clinical diagnosis of this phenotypically variable disease can then be confirmed. © The Author(s) 2015.
Eun Jung Cha
Full Text Available Bartter syndrome (BS I–IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.
Cha, Eun Jung; Hwang, Won Min; Yun, Sung-Ro; Park, Moon Hyang
Bartter syndrome (BS) I-IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.
Full Text Available ObjectiveTo analyze the clinical data, laboratory parameters, infection rate, and serum procalcitonin (PCT and ET-1 levels of patients with cirrhotic ascites and type 1 hepatorenal syndrome (HRS and to investigate the roles of endotoxin and ET-1 in the development of HRS. MethodsBetween January 2009 and October 2012, 56 inpatients with cirrhotic ascites and type 1 HRS (HRS group and 60 inpatients with cirrhotic ascites who had normal renal function (non-HRS group were included in the study. Their general data, causes of liver cirrhosis, infection rates and types, Child-Pugh classification, systemic inflammatory response syndrome (SIRS score, and mean arterial pressure (MAP were recorded; blood samples were collected to evaluate liver and renal function and measure serum electrolyte, PCT, and ET-1 levels. The clinical data and laboratory parameters were compared between the two groups. Categorical data were analyzed by chi-square test; comparison of normally distributed continuous data between the two groups was made by independent-samples t test, and comparison of non-normally distributed continuous data between the two groups was made by Wilcoxon rank sum test. ResultsThe infection rate of HRS group (75.0% was significantly higher than that of non-HRS group (28.4% (χ2=11.91, P＜0.05. The PCT and ET-1 levels and SIRS score of HRS group ［8.72 (3.14, 31.68 ng/L, 13.04±2.82 pg/ml, and 2.1±1.1］ were significantly higher than those of non-HRS group ［0.11 (0.04, 0.45 ng/L, 5.76±1.68 pg/ml, and 0.6±0.6］ (P＜0.05. In addition, the HRS group had significantly higher serum urea, creatine, cystatin C, and K levels than the non-HRS group (P＜0.05, while the HRS group had significantly lower Na and Cl levels than the non-HRS group (P＜0.05. There were no significant differences in ALT and AST levels between the two groups (P＞005. ConclusionEndotoxin causes elevated expression of ET-1, and ET-1 induces renal perfusion deficiency by
Morimoto, Noriko; Mutai, Hideki; Namba, Kazunori; Kaneko, Hiroki; Kosaki, Rika; Matsunaga, Tatsuo
To examine and expand the genetic spectrum of Waardenburg syndrome type 1 (WS1). Clinical features related to Waardenburg syndrome (WS) were examined in a five-year old patient. Mutation analysis of genes related to WS was performed in the proband and her parents. Molecular modeling of EDNRB and the p.R319W mutant was conducted to predict the pathogenicity of the mutation. The proband showed sensorineural hearing loss, heterochromia iridis, and dystopia canthorum, fulfilling the clinical criteria of WS1. Genetic analyses revealed that the proband had no mutation in PAX3 which has been known as the cause of WS1, but had a homozygous missense mutation (p.R319W) in endothelin receptor type B (EDNRB) gene. The asymptomatic parents had the mutation in a heterozygote state. This mutation has been previously reported in a heterozygous state in a patient with Hirschsprung's disease unaccompanied by WS, but the patient and her parents did not show any symptoms in gastrointestinal tract. Molecular modeling of EDNRB with the p.R319W mutation demonstrated reduction of the positively charged surface area in this region, which might reduce binding ability of EDNRB to G protein and lead to abnormal signal transduction underlying the WS phenotype. Our findings suggested that autosomal recessive mutation in EDNRB may underlie a part of WS1 with the current diagnostic criteria, and supported that Hirschsprung's disease is a multifactorial genetic disease which requires additional factors. Further molecular analysis is necessary to elucidate the gene interaction and to reappraise the current WS classification. Copyright © 2017 Elsevier B.V. All rights reserved.
Cortés-González, Vianney; Zenteno, Juan Carlos; Guzmán-Sánchez, Martín; Giordano-Herrera, Verónica; Guadarrama-Vallejo, Dalia; Ruíz-Quintero, Narlly; Villanueva-Mendoza, Cristina
Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Alamgir, Muhammad Ahmad; Javid, Riaz Ahmad; Hameed, Abdul; Mustafa, Irum
Diabetes mellitus, hypertension, obesity and dyslipidemia are the integral components that constitute metabolic syndrome. It has emerged as cause of substantial mortality with gender difference. To compare the gender characteristics of metabolic syndrome in subjects of type 2 diabetes mellitus. This observational comparative prospective study was conducted in medical ward of BVH Bahawalpur over period of 6 month from January 2014 to June 2014. Sample size of 100 diagnosed cases of type 2 diabetics (comprising equal number of males and females) were collected. As defined by WHO and IDF, variables of metabolic syndrome studied were BMI, hypertension, hyperglycemia and hyperlipidemia. The lipid values were interpreted in normal or high risk category by applying NCEP ATPIII criterion. Fasting sample were collected for sugar and lipid profile. Anthropometric, demographic and biochemical data was tabulated. Continuous and categorical variables were displayed as mean ± standard deviation and percentage respectively. Student 't' test was use to assess the difference for the lipid profile at 5% significance level. Female patients were found to be overweight, hypertensive and had uncontrolled hyperglycemia as compared to male subjects. Their systolic blood pressure was 150±25.75 and diastolic was 90±17mm/hg. The mean blood glucose concentration was 246.64±105mg/dl. In age group 35-44 years, the mean triglycerides and cholesterol levels in females were 184.54±42.05 and 192.5±34mg/dl respectively. HDL-C was 33.2±5.19mg/dl. In females with age group of 45-54 years, the mean concentration of triglycerides, total cholesterol and HDL-C were 217.75±77.6mg/dl, 190.95±14.4mg/dl and 31.75±3.8mg/dl respectively, and all were in high risk category when compared to cut off values determined by NCEP/ADA. While in females of age group 55-64 years, the values of TGs, total cholesterol and HDL-C were 204±154.11mg/dl, 200.09± 47.8 mg/dl and 33.4±4.6mg/dl respectively and again
Full Text Available Abstract Background Spinal deformities in Ehlers-Danlos syndrome are usually progressive and may require operative treatment. There is limited number of studies describing late results of surgery in this disease. Methods This is a retrospective study of the records of 11 patients with Ehlers-Danlos syndrome type IV, treated surgically between 1990 and 2007. All patients underwent surgical treatment for spinal deformity. Duration of operation, type of instrumentation, intraoperative blood loss, complications and number of additional surgeries were noted. Radiographic measurement was performed on standing AP and lateral radiographs acquired before surgery, just after and at final follow up. Results The mean follow up period was 5.5 ± 2.9 years (range 1-10 years. The mean preoperative thoracic and lumbar curve were 109.5 ± 19.9° (range 83° - 142° and 75.6 ± 26.7° (range 40° - 108° respectively. Posterior spine fusion alone was performed on 6 patients and combined anterior and posterior fusion (one- or two stage on 5 cases. Posterior segmental spinal instrumentation was applied with use of hooks, screws and wires. The mean postoperative thoracic and lumbar curve improved to 79.3 ± 16.1° (range 56° - 105° and 58.5 ± 27.7° (range 10° - 95° respectively, with a slight loss of correction during follow up. The average thoracic and lumbar correction was 26.4 ± 14.9% (range 5.3 - 50.4% and 26.3 ± 21.2% (range 7.9 - 75%. Postoperatively, the mean kyphosis was 79.5 ± 40.3° (range 21° -170°, and lordosis was 50.8 ± 18.6° (range 20° -79°. Hyperkyphosis increased during follow up while lordosis remained stable. Mean Th12-L2 angle was -3.5 ±9.9° (range -19° - 15° postoperatively and did not change significantly during follow up. Conclusions Huge spinal deformities in patients with Ehlers-Danlos syndrome require complex and extensive surgery. There is a big risk of sagittal imbalance in this group.
Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the
Full Text Available Autosomal dominant hyper IgE syndrome (AD-HIES is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3. This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with Candida and Staphylococcus aureus. It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since S. aureus infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing S. aureus. Using multi-locus sequence typing (MLST, protein A (spa typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 13 found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL, and staphylococcal enterotoxins K and Q (SEK, SEQ. Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors.
Shi, Wan-Yin; Gu, Jian-Ping; Liu, Chang-Jian; Lou, Wen-Sheng; He, Xu
Typical iliac vein compression syndrome (IVCS) is characterized by compression of left common iliac vein (LCIV) by the overlying right common iliac artery (RCIA). We described an underestimated type of IVCS with dual compression by right and left common iliac arteries (LCIA) simultaneously. Thirty-one patients with IVCS were retrospectively included. All patients received trans-catheter venography and computed tomography (CT) examinations for diagnosing and evaluating IVCS. Late venography and reconstructed CT were used for evaluating the anatomical relationship among LCIV, RCIA and LCIA. Imaging manifestations as well as demographic data were collected and evaluated by two experienced radiologists. Sole and dual compression were found in 32.3% (n = 10) and 67.7% (n = 21) of 31 patients respectively. No statistical differences existed between them in terms of age, gender, LCIV diameter at the maximum compression point, pressure gradient across stenosis, and the percentage of compression level. On CT and venography, sole compression was commonly presented with a longitudinal compression at the orifice of LCIV while dual compression was usually presented as two types: one had a lengthy stenosis along the upper side of LCIV and the other was manifested by a longitudinal compression near to the orifice of external iliac vein. The presence of dual compression seemed significantly correlated with the tortuous LCIA (p = 0.006). Left common iliac vein can be presented by dual compression. This type of compression has typical manifestations on late venography and CT.
Walton, K D; Dubois, M; Llinás, R R
Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. The study addresses spontaneous MEG activity from 13 awake, adult patients (2 men, 11 women; age 15-62), with CRPS Type I of one extremity (duration range: 3months to 10years) and from 13 control subjects. All CRPS I patients demonstrated peaks in power spectrum in the delta (CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Ricci, L A; Hodapp, R M
The present study examined fathers' perceptions of, stress relating to and involvement with children with Down's syndrome (DS) (n = 30) versus those with other types of intellectual disability (ID) (n = 20). Fathers and mothers completed questionnaires about their children's personalities and maladaptive behaviours, their own parenting stress, and the fathers' level of involvement. Both fathers and mothers rated their children with DS as having more positive personality traits and fewer maladaptive behaviours. Possibly because of these positive perceptions, fathers of children with DS also reported less child-related stress, particularly in the areas of acceptability, adaptability and demandingness. The two groups of fathers were very similarly involved in child rearing. The personality, age and maladaptive behaviours of the children related to stress levels in the fathers of children with DS, while maladaptive behaviours, gender and the fathers' education levels related to stress levels in the fathers of children with other types of ID. These results highlight the importance of examining parental stress and involvement with children with different types of ID.
O'Sullivan, Eoin P
Antibodies against glutamic acid decarboxylase (GAD) are involved in the pathophysiology of stiff-person syndrome (SPS) and type 1 diabetes. GAD catalyses the conversion of glutamate to gamma-aminobutyric acid (GABA). GABA acts as a neurotransmitter between neurones, while in pancreatic beta cells it plays an integral role in normal insulin secretion, hence the clinical presentation of muscular spasms in SPS and insulin deficiency in diabetes. Despite this apparent major overlap in pathophysiology, SPS only rarely occurs in individuals with type 1 diabetes. We report the case of a 41-year-old man presenting with a simultaneous diagnosis of both these conditions. His case is unusual in that it is the first reported case in the literature of these conditions occurring in someone with celiac disease (CD) and dermatitis herpetiformis. We discuss why SPS and type 1 diabetes co-exist in only a minority of cases and speculate on the underlying mechanism of the association with CD and dermatitis herpetiformis in our patient.
Tian, Guilian; Lee, Richard; Ropelewski, Philip; Imanishi, Yoshikazu
The purpose of this study was to obtain an Usher syndrome type III mouse model with retinal phenotype. Speed congenic method was used to obtain Clrn1 exon 1 knockout (Clrn1-/-) and Clrn1N48K knockin (Clrn1N48K/N48K) mice under A/J background. To study the retinal functions of these mice, we measured scotopic and photopic ERG responses. To observe if there are any structural abnormalities, we conducted light and transmission electron microscopy of fixed retinal specimens. In 3-month-old Clrn1-/- mice, scotopic b-wave amplitude was reduced by more than 25% at the light intensities from -2.2 to 0.38 log cd·s/m2, but scotopic a-wave amplitudes were comparable to those of age-matched wild type mice at all the light intensities tested. In 9-month-old Clrn1-/- mice, scotopic b-wave amplitudes were further reduced by more than 35%, and scotopic a-wave amplitude also showed a small decline as compared with wild type mice. Photopic ERG responses were comparable between Clrn1-/- and wild type mice. Those electrophysiological defects were not associated with a loss of rods. In Clrn1N48K/N48K mice, both a- and b-wave amplitudes were not discernable from those of wild type mice aged up to 10 months. Mutations that are Clrn1-/- biallelic cause visual defects when placed under A/J background. The absence of apparent rod degeneration suggests that the observed phenotype is due to functional defects, and not due to loss of rods. Biallelic Clrn1N48K/N48K mutations did not cause discernible visual defects, suggesting that Clrn1- allele is more severely dysfunctional than ClrnN48K allele.
Zhu, Xiao-Dan; Shen, Zhong-Yang; Chen, Xin-Guo; Zang, Yun-Jin
To summarize the Patho-typing and the clinical manifestation of biliary cast syndrome (BCS) in patients after orthotopic liver transplantation. The clinical manifestation, findings,therapeutic means and efficacy of 103 patients with biliary cast syndrome after orthotopic liver transplantation were retrospectively analyzed. According to the injury level of biliary duct epithelium, patients were divided into different groups. All cases were followed up for twelve months. The place, degree and time after operation would be recorded when non-anastomotic biliary stricture was found. There were 59 BCS cases in the general hospital of armed police force of China. The incidence rate of BCS was 9.1%. Many BCS patients showed symptoms such as jaundice, deep urine color, gray stools, itch of skin and fever. Some were asymptomatic. In laboratory test, the liver functional enzyme in serum were increased, the total white cell count in peripheral blood was increased either. Cholangiography via T tube of biliary tract might show filling defect. According to the change degree of the biliary tract tree, there were four types filling defect concluded from all the presentation in BCS patients. Solid obturation of biliary tract were found by the check with optical fiber choledochoscope in all BCS patients, necrosis of biliary tract epithelium were observed in partial BCS patients. According to the injury level of biliary duct epithelium (gradually aggravated), BCS patients were divided into six groups (type I, type II, type III, type IV, type V and type VI). Fourteen cases were found in type I and 18 in type II. No clinical symptom was found in these two groups, a few indicators in serum (alanine aminotransferase ALT, total bilirubin TBIL, direct bilirubin DBIL) were in normal range, and others (gamma-glutamyl transferase GGT, alkaline phosphatase ALP) were heightened in 5 patients. There was no biliary cast (BC) found anymore in the period of follow-up in two groups. No stricture was
Merone, Lea; McDermott, Robyn
Obesity-fuelled metabolic syndrome and diabetes is now a global epidemic. There is increasing evidence that these and other chronic conditions have common inflammatory antecedents. There is an interest in nutritionally based anti-inflammatory treatments for type 2 diabetes and metabolic syndrome. The aim of this review is to examine the evidence from a 5-year period; 2011-2016, for nutritionally based anti-inflammatory treatments for the Metabolic Syndrome and Type 2 Diabetes Mellitus. A literature search produced a total number of 1377 records, of which 26 papers were evaluated. Literature was analysed and tabulated according to date, outcome measures and results. The evidence is strong for use of polyphenolic compounds, fish oils and vitamins in reducing inflammation biomarkers, however the impact on metabolic control is less evident. Copyright © 2017 Elsevier B.V. All rights reserved.
Kimberling, W J; Möller, C G; Davenport, S; Priluck, I A; Beighton, P H; Greenberg, J; Reardon, W; Weston, M D; Kenyon, J B; Grunkemeyer, J A
Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to chromosome 14q, and this second localization establishes the existence of a new and independent locus for Usher syndrome.
Full Text Available Defects in the rat sarcoma viral oncogene homolog (Ras/extracellular-signal-regulated kinase (ERK and the phosphatidylinositol 3-kinase (PI3K-mammalian target of rapamycin (mTOR signaling pathways are responsible for several neurodevelopmental disorders. These disorders are an important cause for intellectual disability; additional manifestations include autism spectrum disorder, seizures and brain malformations. Changes in synaptic function are thought to underlie the neurological conditions associated with these syndromes. We therefore studied morphology and in vivo synaptic transmission of the calyx of Held synapse, a relay synapse in the medial nucleus of the trapezoid body (MNTB of the auditory brainstem, in mouse models of Tuberous sclerosis (TSC, Fragile X syndrome (FXS, Neurofibromatosis type 1 (NF1 and Costello syndrome (CS. Calyces from both Tsc1+/- and from Fmr1 knock-out (KO mice showed increased volume and surface area compared to wild-type (WT controls. In addition, in Fmr1 KO animals a larger fraction of calyces showed complex morphology. In MNTB principal neurons of Nf1+/- mice the average delay between EPSPs and APs was slightly smaller compared to wild-type controls, which could indicate an increased excitability. Otherwise, no obvious changes in synaptic transmission or short-term plasticity were observed during juxtacellular recordings in any of the four lines. Our results in these four mutants thus indicate that abnormalities of mTOR or Ras signaling do not necessarily result in changes in in vivo synaptic transmission.
I. V. Zapuskalov
Full Text Available This article analyzes the current state of the problem of the correction of anophthalmic syndrome. Evaluated various methods of formation of the locomotor stump after removal of the eyeball, gave a detailed description of different types of materials for the fabrication of orbital implant, as well as reflect the basic principles of prevention of complications.
Hendriks, Steven H.; van Dijk, Peter R.; Groenier, Klaas H.; Houpt, Peter; Bilo, Henk J. G.; Kleefstra, Nanne
BACKGROUND: Previous studies have shown that the carpal tunnel syndrome seems to occur more frequently in patients with diabetes mellitus and might be associated with the duration of diabetes mellitus, microvascular complications and degree of glycaemic control. Primary aim was to determine if type
Guillem, Maria S; Climent, Andreu M; Millet, José; Berne, Paola; Ramos, Rafael; Brugada, Josep; Brugada, Ramon
The diagnosis of Brugada syndrome based on the ECG is hampered by the dynamic nature of its ECG manifestations. Brugada syndrome patients are only 25% likely to present a type 1 ECG. The objective of this study is to provide an ECG diagnostic criterion for Brugada syndrome patients that can be applied consistently even in the absence of a type 1 ECG. We recorded 67-lead body surface potential maps from 94 Brugada syndrome patients and 82 controls (including right bundle branch block patients and healthy individuals). The spatial propagation direction during the last r' wave and the slope at the end of the QRS complex were measured and compared between patients groups. Receiver-operating characteristic curves were constructed for half of the database to identify optimal cutoff values; sensitivity and specificity for these cutoff values were measured in the other half of the database. A spontaneous type 1 ECG was present in only 30% of BrS patients. An orientation in the sagittal plane ECG recordings can enable a robust identification of BrS even without the presence of a type 1 ECG. © 2016 Wiley Periodicals, Inc.
Ethan, Danna; Rennis, Lesley; Samuel, Lalitha; Seidel, Erica J.; Basch, Corey H.
Objective: Type 2 diabetes, prediabetes, and metabolic syndrome are increasingly relevant health problems for United States (US) college-aged students and their family members. This study's aim was to determine the extent to which these chronic conditions were covered in leading college-level personal health textbooks and to what degree the…
Kemler, MA; Reulen, JPH; Barendse, GAM; van Kleef, M; de Vet, HCW; van den Wildenberg, FAJM
Background: A randomized trial was performed to assess the effect of spinal cord stimulation (SCS) on detection and pain thresholds for pressure, warmth, and cold and on the extent of mechanical hyperalgesia in patients with chronic complex regional pain syndrome type I. Methods: Fifty-four chronic
Møller, Katrine Dragsbæk; Neergaard, Jesper; Laursen, Janne Marie
The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM...
Weston, M.D.; Luijendijk, M.W.J.; Humphrey, K.D.; Moller, C.G.; Kimberling, W.J.
Usher syndrome type II (USH2) is a genetically heterogeneous autosomal recessive disorder with at least three genetic subtypes (USH2A, USH2B, and USH2C) and is classified phenotypically as congenital hearing loss and progressive retinitis pigmentosa. The VLGR1 (MASS1) gene in the 5q14.3-q21.1 USH2C
DeFina, Laura F; Vega, Gloria Lena; Leonard, David; Grundy, Scott M
To determine risk for type 2 diabetes in subjects with fasting glucose levels in the ranges of normoglycemia, mild hyperglycemia, and intermediate hyperglycemia and to assess the effect of obesity and metabolic syndrome on this risk. Incidence of type 2 diabetes mellitus was evaluated in 28,209 relatively healthy subjects participating in the Cooper Center Longitudinal Study. They were included in the study if they had more than 1 fasting plasma glucose measurement, anthropometry, and other parameters of interest. Three subgroups were identified: normoglycemic (obesity, and metabolic syndrome status. Incident diabetes was assessed at the earliest clinic visit at which the individual exhibited a blood glucose level of more than 7.0 mmol/L or reported a diagnosis of diabetes. Thirty-one percent of men and 15.9% of women had mild hyperglycemia and 11.9% of men and 3.6% of women had intermediate hyperglycemia. Yearly conversion rates to diabetes were low in individuals with normoglycemia and mild hyperglycemia but were strikingly higher in those with intermediate hyperglycemia. In subjects with intermediate hyperglycemia, presence of obesity and/or metabolic syndrome doubled conversion rates to diabetes. This study showed a marked difference in outcomes in subjects with mild and intermediate hyperglycemia. Moreover, obesity and metabolic syndrome were associated with strikingly elevated risk for diabetes in subjects with intermediate hyperglycemia. Thus intermediate hyperglycemia plus obesity/metabolic syndrome seemingly justifies intensive clinical intervention for prevention of both diabetes and cardiovascular disease.
Ekvall, Sara; Sjörs, Kerstin; Jonzon, Anders; Vihinen, Mauno; Annerén, Göran; Bondeson, Marie-Louise
Neurofibromatosis-Noonan syndrome (NFNS) is a rare condition with clinical features of both neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). All three syndromes belong to the RASopathies, which are caused by dysregulation of the RAS-MAPK pathway. The major gene involved in NFNS is NF1, but co-occurring NF1 and PTPN11 mutations in NFNS have been reported. Knowledge about possible involvement of additional RASopathy-associated genes in NFNS is, however, very limited. We present a comprehensive clinical and molecular analysis of eight affected individuals from three unrelated families displaying features of NF1 and NFNS. The genetic etiology of the clinical phenotypes was investigated by mutation analysis, including NF1, PTPN11, SOS1, KRAS, NRAS, BRAF, RAF1, SHOC2, SPRED1, MAP2K1, MAP2K2, and CBL. All three families harbored a heterozygous NF1 variant, where the first family had a missense variant, c.5425C>T;p.R1809C, the second family a recurrent 4bp-deletion, c.6789_6792delTTAC;p.Y2264Tfs*6, and the third family a splice-site variant, c.2991-1G>A, resulting in skipping of exon 18 and an in-frame deletion of 41 amino acids. These NF1 variants have all previously been reported in NF1 patients. Surprisingly, both c.6789_6792delTTAC and c.2991-1G>A are frequently associated with NF1, but association to NFNS has, to our knowledge, not previously been reported. Our results support the notion that NFNS represents a variant of NF1, genetically distinct from NS, and is caused by mutations in NF1, some of which also cause classical NF1. Due to phenotypic overlap between NFNS and NS, we propose screening for NF1 mutations in NS patients, preferentially when café-au-lait spots are present. © 2013 Wiley Periodicals, Inc.
Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F
Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.
Jaschinski, Wolfgang; König, Mirjam; Mekontso, Tiofil M; Ohlendorf, Arne; Welscher, Monique
This office field study investigated the effects of different types of spectacle lenses habitually worn by computer users with presbyopia and in the beginning stages of presbyopia. Computer vision syndrome was assessed through reported complaints and ergonomic conditions. A questionnaire regarding the type of habitually worn near-vision lenses at the workplace, visual conditions and the levels of different types of complaints was administered to 175 participants aged 35 years and older (mean ± SD: 52.0 ± 6.7 years). Statistical factor analysis identified five specific aspects of the complaints. Workplace conditions were analysed based on photographs taken in typical working conditions. In the subgroup of 25 users between the ages of 36 and 57 years (mean 44 ± 5 years), who wore distance-vision lenses and performed more demanding occupational tasks, the reported extents of 'ocular strain', 'musculoskeletal strain' and 'headache' increased with the daily duration of computer work and explained up to 44 per cent of the variance (rs = 0.66). In the other subgroups, this effect was smaller, while in the complete sample (n = 175), this correlation was approximately rs = 0.2. The subgroup of 85 general-purpose progressive lens users (mean age 54 years) adopted head inclinations that were approximately seven degrees more elevated than those of the subgroups with single vision lenses. The present questionnaire was able to assess the complaints of computer users depending on the type of spectacle lenses worn. A missing near-vision addition among participants in the early stages of presbyopia was identified as a risk factor for complaints among those with longer daily durations of demanding computer work. © 2015 The Authors. Clinical and Experimental Optometry © 2015 Optometry Australia.
Abbott, Jamie A; Guth, Ethan; Kim, Cindy; Regan, Cathy; Siu, Victoria M; Rupar, C Anthony; Demeler, Borries; Francklyn, Christopher S; Robey-Bond, Susan M
Histidyl-tRNA synthetase (HARS) is a highly conserved translation factor that plays an essential role in protein synthesis. HARS has been implicated in the human syndromes Charcot-Marie-Tooth (CMT) Type 2W and Type IIIB Usher (USH3B). The USH3B mutation, which encodes a Y454S substitution in HARS, is inherited in an autosomal recessive fashion and associated with childhood deafness, blindness, and episodic hallucinations during acute illness. The biochemical basis of the pathophysiologies linked to USH3B is currently unknown. Here, we present a detailed functional comparison of wild-type (WT) and Y454S HARS enzymes. Kinetic parameters for enzymes and canonical substrates were determined using both steady state and rapid kinetics. Enzyme stability was examined using differential scanning fluorimetry. Finally, enzyme functionality in a primary cell culture was assessed. Our results demonstrate that the Y454S substitution leaves HARS amino acid activation, aminoacylation, and tRNA His binding functions largely intact compared with those of WT HARS, and the mutant enzyme dimerizes like the wild type does. Interestingly, during our investigation, it was revealed that the kinetics of amino acid activation differs from that of the previously characterized bacterial HisRS. Despite the similar kinetics, differential scanning fluorimetry revealed that Y454S is less thermally stable than WT HARS, and cells from Y454S patients grown at elevated temperatures demonstrate diminished levels of protein synthesis compared to those of WT cells. The thermal sensitivity associated with the Y454S mutation represents a biochemical basis for understanding USH3B.
García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Álvaro; Chocrón, Sara; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; García Nieto, Víctor; Barajas de Frutos, David; Loza, Reyner; Pintos, Guillem; Castaño, Luis; Ariceta, Gema
Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS. Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses. Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype. A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.
Alejandro García Castaño
Full Text Available Type III Bartter syndrome (BS is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS.Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses.Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG in one patient and a small deletion (c.1026delC in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype.A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohort.
Crone, Clarissa; Christiansen, Ingelise; Vissing, John
Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. A few reports have described that EMG in LEMS may show changes compatible with myopathy, and muscle biopsies have been described with type II as well as type I atrophy. The EMG results were, however, based on ...... on qualitative EMG examination and the histopathological methods were not always clear. The objective of this study was to investigate if the previous EMG findings could be confirmed with quantitative EMG (QEMG) and to describe muscle histology in LEMS.......Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. A few reports have described that EMG in LEMS may show changes compatible with myopathy, and muscle biopsies have been described with type II as well as type I atrophy. The EMG results were, however, based...
Full Text Available Purpose: to determine the peculiarities of the functional state of cardiorespiratory system in women with postmastectomy syndrome with different types of attitude to the disease. Material and Methods: analysis of the literature and empirical data; rheography, spirography, the definition of the type of attitude to the disease of personality questionnaires of Institute of Behtereva; methods of mathematical statistics. 115 women with postmastectomy syndrome on clinical stage of rehabilitation were involved in this study. Results: in women with intra- and interpsychic types of attitude to the disease decreased reserve capacity of the cardiovascular and respiratory systems respectively. Conclusions: It was proved that women with a rational relationship to the type of disease show significantly better results of the cardiovascular system compared to interpsychic and intrapsychic.
Hakim, Alan; O'Callaghan, Chris; De Wandele, Inge; Stiles, Lauren; Pocinki, Alan; Rowe, Peter
Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS-related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt-table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non-pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short-term physiological studies. Pharmacologic therapy is indicated for patients with moderate-severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more general evaluation and on-going management and support. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
De Baets, Stijn; Vanhalst, Marieke; Coussens, Marieke; Rombaut, Lies; Malfait, Fransiska; Van Hove, Geert; Calders, Patrick; Vanderstraeten, Guy; van de Velde, Dominique
The consequences of the Ehlers-Danlos Syndrome hypermobility type (EDS-HT) affect many aspects of daily life. "Living with limitations" is a central theme in the life of patients affected by this heritable disorder of connective tissue. The aim of the present study was to explore the lived experiences of women with EDS-HT concerning diagnosis, influence on daily life and becoming and being a mother. A phenomenological-hermeneutical study, using in-depth interviews. Patients were selected by a purposive sampling strategy. This study shows that the EDS-HT syndrome affects daily life. Ten woman between 31 and 65 years were interviewed. They have between 2 and 5 children. The data analysis results in six themes. (1) Getting a diagnosis is a relief and supports the choice to become a mother; (2) EDS-HT causes emotional distress, imposes a physical burden and has a major impact on social behavior; (3) EDS-HT demands a restructuring of everyday activities; (4) Children's and mothers' expectations do not correspond; (5) Having a supportive social and physical environment is of major importance; (6) The presence of the child reduces the feeling of illness of the mother. The diagnosis of EDS-HT is a catalysing factor in the choice of whether or not to become a mother. EDS-HT has a huge impact on bodily functions, which in turn influences activities and participation. This study gives insight in the activities of daily life of persons with EDS-HT. Health care professionals can be of great importance to help patients in (re)organizing their lives according to the available energy and in supporting their choices. They can help defining goals and setting priorities in daily life. Copyright © 2016 Elsevier Ltd. All rights reserved.
Billow, Amy; Anjana, Ranjit Mohan; Ngai, Michelle; Amutha, Anandakumar; Pradeepa, Rajendra; Jebarani, Saravanan; Unnikrishnan, Ranjit; Michael, Edwin; Mohan, Viswanathan
To assess the prevalence of metabolic syndrome (MetS) among patients with type 1 diabetes mellitus(T1DM) and to look at prevalence of diabetes complications in T1DM with and without MetS. We studied 451 T1DM patients attending a tertiary diabetes centre in Chennai, South India. T1DM was diagnosed based on absence of beta cell reserve and requirement of insulin from the time of diagnosis. Data on clinical and biochemical characteristics as well as complications details to study the prevalence were also extracted from electronic records. T1DM patients were divided into those with and without MetS[diagnosed according to the harmonizing the metabolic syndrome criteria(IDF/NHLBI/AHA/WHF/IAS/IASO)]. The overall prevalence of MetS among T1DM was 22.2%(100/451). Patients with MetS were older, had longer diabetes duration, acanthosis nigricans, and increased serum cholesterol. In the unadjusted logistic regression analysis, retinopathy, nephropathy and neuropathy were associated with MetS. However after adjustment for age, gender, diabetes duration, HbA1C and BMI significant association was seen only between MetS and retinopathy [odds ratio (OR) 2.82, 95% CI 1.18-6.74, p = 0.020] and nephropathy [OR 4.92, 95% CI 2.59-9.33, p < 0.001]. Prevalence of MetS is high among Asian Indian T1DM patients, and its presence is associated with increased risk of diabetic retinopathy and nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.
Budyal, Sweta; Jadhav, Swati Sachin; Kasaliwal, Rajeev; Patt, Hiren; Khare, Shruti; Shivane, Vyankatesh; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S
Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in patients with type 2 diabetes mellitus (T2DM), making the need for screening in this population uncertain. It is unknown if this variability is solely due to study-related methodological differences or a reflection of true differences in ethnic predisposition. The objective of this study is to explore the prevalence of SCS in Asian Indian patients with T2DM. In this prospective single center study conducted in a tertiary care referral center, 993 T2DM outpatients without any discriminatory clinical features (easy bruising, facial plethora, proximal muscle weakness, and/or striae) of hypercortisolism underwent an overnight 1 mg dexamethasone suppression test (ODST). ODST serum cortisol ≥1.8 μg/dl was considered positive, and those with positive results were subjected to 48 h, 2 mg/day low dose DST (LDDST). A stepwise evaluation for endogenous hypercortisolism was planned for patients with LDDST serum cortisol ≥1.8 μg/dl. Patients with positive ODST and negative LDDST were followed up clinically and re-evaluated a year later for the development of clinically evident Cushing's syndrome (CS). In this largest single center study reported to date, we found 37 out of 993 (3.72%) patients had ODST serum cortisol ≥1.8 μg/dl. None of them had LDDST cortisol ≥1.8 μg/dl, nor did they develop clinically evident CS over a follow-up period of 1 year. Specificity of ODST for screening of CS was 96.3% in our cohort. None of the T2DM outpatients in our cohort had SCS, hence cautioning against routine biochemical screening for SCS in this cohort. We suggest screening be based on clinical suspicion only. PMID:26420669
Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos
Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.
Mitra, Arijit; Ramakrishnan, R; Kader, Mohideen Abdul
A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA) of hand movement (HM) in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD) in right eye. Intraocular pressure (IOP) was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA) in right eye and cup disc ratio (CDR) of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS) with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.
Full Text Available A 26-year-old male presented to us with defective vision in the left eye. He had best corrected visual acuity (BCVA of hand movement (HM in right eye and 6/9 in left eye. He had ptosis with ectropion in both eyes and relative afferent pupillary defect (RAPD in right eye. Intraocular pressure (IOP was 46 and 44 mmHg in right and left eye, respectively. Fundus showed glaucomatous optic atrophy (GOA in right eye and cup disc ratio (CDR of 0.75 with bipolar rim thinning in left eye. Systemic examination showed hyperextensible skin and joints, acrogeria, hypodontia, high arched palate, and varicose veins. He gave history of easy bruising and tendency to fall and history of intestinal rupture 5 years ago for which he had undergone surgery. He was diagnosed as a case of Type IV Ehler-Danlos syndrome (EDS with open angle glaucoma. He underwent trabeculectomy in both eyes. This is a rare case that shows glaucoma in a patient of EDS Type IV. Very few such cases have been reported in literature.
Pietola, Laura; Aarnisalo, Antti A; Abdel-Rahman, Akram; Västinsalo, Hanna; Isosomppi, Juha; Löppönen, Heikki; Kentala, Erna; Johansson, Reijo; Valtonen, Hannu; Vasama, Juha-Pekka; Sankila, Eeva-Marja; Jero, Jussi
Usher syndrome Type 3 (USH3) is an autosomal recessive disorder characterized by variable type and degree of progressive sensorineural hearing loss and retinitis pigmentosa. Cochlear implants are widely used among these patients. To evaluate the results and benefits of cochlear implantation in patients with USH3. A nationwide multicenter retrospective review. During the years 1995-2005, in 5 Finnish university hospitals, 19 patients with USH3 received a cochlear implant. Saliva samples were collected to verify the USH3 genotype. Patients answered to 3 questionnaires: Glasgow Benefit Inventory, Glasgow Health Status Inventory, and a self-made questionnaire. Audiological data were collected from patient records. All the patients with USH3 in the study were homozygous for the Finnish major mutation (p.Y176X). Either they had severe sensorineural hearing loss or they were profoundly deaf. The mean preoperative hearing level (pure-tone average, 0.5-4 kHz) was 110 ± 8 dB hearing loss (HL) and the mean aided hearing level was 58 ± 11 dB HL. The postoperative hearing level (34 ± 9 dB HL) and word recognition scores were significantly better than before surgery. According to the Glasgow Benefit Inventory scores and Glasgow Health Status Inventory data related to hearing, the cochlear implantation was beneficial to patients with USH3. Cochlear implantation is beneficial to patients with USH3, and patients learn to use the implant without assistance.
Full Text Available Ehlers-Danlos syndrome, vascular type (vEDS (MIM #130050 is an autosomal dominant disorder caused by mutation in the type III collagen gene, COL3A1, leading to fragility of blood vessels, bowel and uterus that leads to spontaneous rupture. We report a previously undiagnosed vEDS patient with bowel complications. A 20-year-old female patient was referred to our hospital with abdominal pain. Computed tomography showed notable dilatation of the sigmoid colon with intraperitoneal fluid. Laparotomy revealed dilatation of the sigmoid colon, breakdown of serosa and muscularis propria of the sigmoid colon with impending perforation, and intra-abdominal hemorrhage caused by breakdown of the mesenterium. Resection of the sigmoid colon with Hartmann's pouch and an end colostomy were performed. Physical examination showed joint hypermobility, translucent skin with venous prominence and facial structure abnormalities. Genetic analysis using cDNA extracted from the patient's fibroblasts by reverse transcriptase polymerase chain reaction direct sequencing showed a missense mutation within the triple helix region of COL3A1 (c.2150 G>A; Gly717Asp.
Monti, D A; Herring, C L; Schwartzman, R J; Marchese, M
There is controversy regarding the importance of psychological/psychiatric factors in the development of the Complex Regional Pain Syndrome (CRPS). Our objective was to determine whether CRPS type I patients were psychiatrically different from other chronic pain patients, with particular attention to personality pathology. A standardized clinical assessment of all major psychiatric categories, including personality disorders, was performed on 25 CRPS type I patients and a control group of 25 patients with chronic low back pain from disc-related radiculopathy. Both sections of the Structured Clinical Interview for the Diagnostic and Statistical Manual (3rd ed., rev.) and the visual analog scale. Both groups were similar in terms of pain intensity and duration. Statistical analysis showed both groups to have a significant amount of major psychiatric comorbidity, in particular major depressive disorder, and a high incidence of personality disorders. Therefore, intense chronic pain was associated with significant psychiatric comorbidity in both groups and in similar proportions. The high incidence of personality pathology in both groups may represent an exaggeration of maladaptive personality traits and coping styles as a result of a chronic, intense, state of pain.
Ahmed, Zubair M; Smith, Tenesha N; Riazuddin, Saima; Makishima, Tomoko; Ghosh, Manju; Bokhari, Sirosh; Menon, Puthezhath S N; Deshmukh, Dilip; Griffith, Andrew J; Riazuddin, Sheikh; Friedman, Thomas B; Wilcox, Edward R
Human chromosome 11 harbors two Usher type I loci, USHIB and USHIC, which encode myosin VIIA and harmonin, respectively. The USHIC locus overlaps the reported critical interval for nonsyndromic deafness locus DFNB18. We found an IVS12+5G-->C mutation in the USHIC gene, which is associated with nonsyndromic recessive deafness ( DFNB18) segregating in the original family, S-11/12. No other disease-associated mutation was found in the other 27 exons or in the intron-exon boundaries, and the IVS12+5G-->C mutation was not present in 200 representative unaffected individuals ascertained from the same area of India. An exon-trapping assay with a construct harboring IVS12+5G-->C generated wildtype spliced mRNA having exons 11 and 12 and mRNA that skipped exon 12. We conclude that mutations of USHIC can cause both Usher syndrome type IC and nonsyndromic recessive deafness DFNB18.
Falk, Dean; Hildebolt, Charles; Smith, Kirk; Jungers, William; Larson, Susan; Morwood, Michael; Sutikna, Thomas; Jatmiko; Saptomo, E Wahyu; Prior, Fred
The type specimen (LB1) of Homo floresiensis has been hypothesized to be a pathological human afflicted with Laron Syndrome (LS), a type of primary growth hormone insensitivity (Hershkovitz et al.: Am J Phys Anthropol 134  198-208). Comparing measurements, photographs and three-dimensional, computed-tomography reconstructions of LB1 with data and diagnoses from the literature on LS, we critically evaluate numerous skull and postcranial traits that Hershkovitz et al. identified as being shared by LB1 and patients with LS. The statements regarding most of these traits are new to the clinical literature and lack quantitative support. LB1 and patients with LS differ markedly in the size and shape of the cranium; thickness and pneumatization of cranial bones; morphology of the face, mandible, teeth, and chin; form of the shoulder, wrist, and pelvis; and general body proportions including relative foot size. Claims that patients with LS are similar to LB1 in displaying protracted scapulae, short clavicles, low degrees of humeral torsion, flaring ilia, and curved tibiae are not supported by data or corroborating images. Some points of similarity (e.g., femoral neck-shaft angle, femoral bicondylar angle, and estimated stature) can be found in other hominins, and cannot be considered diagnostic. From our review and analysis, we conclude that LB1 did not suffer from LS. Copyright 2009 Wiley-Liss, Inc.
Full Text Available Introduction. Cerebro-costo-mandibular syndrome (CCMS is a rare disorder, with only 75 cases described in the literature to date. CCMS is characterized by association of micrognathia and specific multiple rib defects. It is accompanied by mental deficiency in considerable number of cases. Sometimes, there are associated anomalies and problems, such as spine deformities, brain, heart, kidney or ear anomalies, feeding difficulties, delayed psychomotor development, and growth impairment. Depending on severity of deformities and consecutive respiratory insufficiency, in about 35-50% of CCMS cases, death occurs during the first year of life. These cases are referred to as severe types of CCMS. Case Outline. In this paper we present a female infant with severe type of CCMS. Diagnosis was established in the first day of life, based on micrognathia and findings of posterior rib-gap defects on the chest X-ray, accompanied by dyspnea. Progressive severe respiratory insufficiency caused by chest and air-way deformities and exacerbated by episodes of pneumonia, led to respiratory failure and death at the age of 7.5 months. Conclusion. CCMS should be considered in every infant with micrognathia and rib-gap defects on chest X-ray.
Matić, Aleksandra; Velisavljev-Filipović, Gordana; Lovrenski, Jovan; Gajdobranski, Djordje
Cerebro-costo-mandibular syndrome (CCMS) is a rare disorder, with only 75 cases described in the literature to date. CCMS is characterized by association of micrognathia and specific multiple rib defects. It is accompanied by mental deficiency in considerable number of cases. Sometimes, there are associated anomalies and problems, such as spine deformities, brain, heart, kidney or ear anomalies, feeding difficulties, delayed psychomotor development, and growth impairment. Depending on severity of deformities and consecutive respiratory insufficiency, in about 35–50% of CCMS cases, death occurs during the first year of life. These cases are referred to as severe types of CCMS. In this paper we present a female infant with severe type of CCMS. Diagnosis was established in the first day of life, based on micrognathia and findings of posterior rib-gap defects on the chest X-ray, accompanied by dyspnea. Progressive severe respiratory insufficiency caused by chest and air-way deformities and exacerbated by episodes of pneumonia, led to respiratory failure and death at the age of 7.5 months. CCMS should be considered in every infant with micrognathia and rib-gap defects on chest X-ray.
Ma, Chun-Ming; Lu, Na; Wang, Rui; Liu, Xiao-Li; Lu, Qiang; Yin, Fu-Zai
The present study evaluated the performance of three novel obese indicators, visceral adiposity index (VAI), lipid accumulation product (LAP) and waist circumference-triglyceride index (WTI), for identifying metabolic syndrome(MetS) in type 2 diabetes. A cross-sectional study was conducted on 711 type 2 diabetes in Qinhuangdao. The MetS was defined as the definition of Chinese Diabetes Society. Receiver operating characteristic curve analyses were performed to assess the accuracy of three obese indicators as diagnostic tests for MetS. The prevalence of MetS was 71.3%. In men, among all three obese indicators, the LAP had the highest area under curve (AUC) value (AUC = 0.894), followed by VAI (AUC = 0.860) and WTI (AUC = 0.855). In women, among all three obese indicators, the LAP had the highest AUC value (AUC = 0.906), followed by WTI (AUC = 0.887) and VAI (AUC = 0.881). However. there was no significant difference between the three obese indicators(P > 0.05). Three obese indicators were effective indicators for the screening of MetS, LAP and WTI are more simple.
Fretzayas, Andreas; Gole, Evangelia; Attilakos, Achilleas; Daskalaki, Anna; Nicolaidou, Polyxeni; Papadopoulou, Anna
Bartter syndrome (BS) is a group of genetic disorders characterized by hypokalemic metabolic alkalosis, hyponatremia and elevated renin and aldosterone plasma concentrations. BS type II is caused by mutations in the KCNJ1 gene and usually presents with transient hyperkalemia. We report here a novel KCNJ1 mutation in a male neonate, prematurely born after a pregnancy complicated by polyhydramnios. The infant presented with typical clinical and laboratory findings of BS type II, such as hyponatremia, hypochloremic metabolic alkalosis, severe weight loss, elevated renin and aldosterone levels and transient hyperkalemia in the early postnatal period, which were later normalized. Molecular analysis revealed a compound heterozygous mutation in the KCNJ1 gene, consisting of a novel K76E and an already described V315G mutation, both affecting functional domains of the channel protein. Typical manifestations of antenatal BS in combination with hyperkalemia should prompt the clinician to search for mutations in the KCNJ1 gene first. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.
Astuto, L M; Weston, M D; Carney, C A; Hoover, D M; Cremers, C W; Wagenaar, M; Moller, C; Smith, R J; Pieke-Dahl, S; Greenberg, J; Ramesar, R; Jacobson, S G; Ayuso, C; Heckenlively, J R; Tamayo, M; Gorin, M B; Reardon, W; Kimberling, W J
Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.
Tichelaar, Y. I. G. Vladimir; Geertzen, Jan H. B.; Keizer, Doeke; van Wilgen, C. Paul
Complex regional pain syndrome type I is a disorder of the extremities with disability and pain as the most prominent features. This paper describes the results of cognitive behavioural therapy combined with mirror box therapy in three patients with chronic complex regional pain syndrome type I.
Full Text Available Abstract Introduction Vascular-type Ehlers-Danlos syndrome is an autosomal dominant disease that causes arterial spurting, intestinal perforation, uterine rupture and hemopneumothorax due to decreased production of type III collagen. The average age at death is 48 years old, and it is considered to be the most severe form of Ehlers-Danlos syndrome. We report the case of a 64-year-old Japanese woman and her 38-year-old daughter who were diagnosed with this disease. Case presentation A 64-year-old Japanese woman was referred to our hospital because of right anterior chest pain following cough and pharyngeal discomfort. Pleurisy was suspected due to the presence of right pleural effusion, so the next day she was referred to our department, where a detailed examination led to the diagnosis of hemothorax. The bleeding that caused the right hemothorax was difficult to control, so our patient was transferred to the Department of Thoracic Surgery for hemostasis control. Our patient’s personal history of uterine hemorrhage and skin ulcers, as well as the finding of skin fragility during surgery, were indicative of a weak connective tissue disease; therefore, after improvement of the hemothorax, a genetic analysis was performed. This revealed a heterozygous missense mutation in COL3A1, c.2411 G>T p.Gly804Val (exon 36. A detailed investigation conducted at a later date revealed that her daughter also had the same genetic mutation. This led to the diagnosis of vascular-type Ehlers-Danlos syndrome characterized by a new gene mutation. Conclusion We report a new genetic mutation associated with vascular-type Ehlers-Danlos syndrome. We present the clinical and imaging findings, and the disease and treatment course in this patient. We believe this information will be important in treating future cases of vascular-type Ehlers-Danlos syndrome in patients with this mutation.
Mondon, K; de Toffol, B; Georgesco, G; Cassarini, J-F; Machet, M-C; Cottier, J-P; Arbeille, B; Autret, A
Dissection of cervical arteries is a frequent cause of stroke in young subjects. We report the case of a 34-year-old patient who experienced simultaneous dissection of both internal carotid arteries and both vertebral arteries leading to repeated motor deficit of the right half-body associated with persistent otalgia. Search for an etiology led to the diagnosis of Ehlers-Danlos syndrome type IV. Search for the cause of cervical artery dissection must consider connective tIssue disease, particularly vascular forms of Ehler-Danlos syndrome. Diagnostic, therapeutic as well as prognostic aspects are discussed.
Full Text Available Summary Complex regional pain syndrome is a chronic syndrome characterised with dystrophic changes and neurovascular disordes of bone and skin of extremities. The most common etiological factors are trauma, ischemic heart disease, cerebral lesions, servical region disorders, infections, and surgical treatments. Carpal tunnel syndrome is the most common compressive neuropaty of the upper extremity. There are various surgical and conservative alternatives in the treatment of carpal tunnel syndrome. Complex regional pain syndrome has been reported as a complication of surgical carpal tunnel release in 2-5% of patients. In this case report clinical characteristics and rehabilitation outcomes of a patient with complex regional pain syndrome after carpal tunnel release surgery is presented. (Osteoporoz Dünyasından 2010;16:41-3
Full Text Available Abstract Introduction Colonoscopic perforation is a rare but serious complication of colonoscopy. Factors known to increase the risk of perforation include colonic strictures, extensive diverticulosis, and friable tissues. We describe the case of a man who was found to have perforation of the sigmoid colon secondary to an undiagnosed connective tissue disorder (Ehlers-Danlos syndrome type IV while undergoing surveillance for hereditary non-polyposis colorectal cancer. Case presentation A 33-year-old Caucasian man presented to our hospital with an acute abdomen following a colonoscopy five days earlier as part of hereditary non-polyposis colorectal cancer screening. His medical history included bilateral clubfoot. His physical examination findings suggested left iliac fossa peritonitis. A computed tomographic scan revealed perforation of the sigmoid colon and incidentally a right common iliac artery aneurysm as well. Hartmann's procedure was performed during laparotomy. The patient recovered well post-operatively and was discharged. Reversal of the Hartmann's procedure was performed six months later. This procedure was challenging because of dense adhesions and friable bowel. The histology of bowel specimens from this surgery revealed thinning and fibrosis of the muscularis externa. The patient was subsequently noted to have transparency of truncal skin with easily visible vessels. An underlying collagen vascular disorder was suspected, and genetic testing revealed a mutation in the collagen type III, α1 (COL3A1 gene, which is consistent with a diagnosis of Ehlers-Danlos syndrome type IV. Conclusions Ehlers-Danlos syndrome type IV, the vascular type, is a rare disorder caused by mutations in the COL3A1 gene on chromosome 2q31. It is characterized by translucent skin, clubfoot, and the potentially fatal complications of spontaneous large vessel rupture, although spontaneous uterine and colonic perforations have also been reported in the
Zhang, Hua; Chen, Hongsheng; Feng, Yong; Qian, Minfei; Li, Jiping; Liu, Jun; Zhang, Chun
To explore the molecular mechanism of Waardenburg syndrome type II (WS2) resulting from SOX10 gene mutation E248fs through in vitro experiment. 293T cells were transiently transfected with wild type (WT) SOX10 and mutant type (MT) E248fs plasmids. The regulatory effect of WT/MT SOX10 on the transcriptional activity of MITF gene and influence of E248fs on WT SOX10 function were determined with a luciferase activity assay. The DNA binding capacity of the WT/MT SOX10 with the promoter of the MITF gene was determined with a biotinylated double-stranded oligonucleotide probe containing the SOX10 binding sequence cattgtc to precipitate MITF and E248fs, respectively. The stability of SOX10 and E248fs were also analyzed. As a loss-of-function mutation, the E248fs mutant failed to transactivate the MITF promoter as compared with the WT SOX10 (P<0.01), which also showed a dominant-negative effect on WT SOX10. The WT SOX10 and E248fs mutant were also able to bind specifically to the cattgtc motif in the MITF promoter, whereas E248fs had degraded faster than WT SOX10. Despite the fact that the E248fs has a dominant-negative effect on SOX10, its reduced stability may down-regulate the transcription of MITF and decrease the synthesis of melanin, which may result in haploinsufficiency of SOX10 protein and cause the milder WS2 phenotype.
Zmyslowska, A; Borowiec, M; Fichna, P; Iwaniszewska, B; Majkowska, L; Pietrzak, I; Szalecki, M; Szypowska, A; Mlynarski, W
Improvements in diagnostic methods and greater genetic awareness have brought remarkable progress in the recognition of monogenic forms of diabetes, including Wolfram syndrome (WFS). WFS is diagnosed based on clinical criteria of coexistence of diabetes mellitus and optic atrophy, and confirmed by molecular analysis; however, the condition is still sometimes misdiagnosed. To begin to understand the reasons for misdiagnosis, we conducted a retrospective analysis of WFS patients who were originally misdiagnosed. The medical histories of 13 pediatric patients with clinical misdiagnosis of type 1 diabetes and early chronic complications made in the years 1995-2010 and who were subsequently correctly diagnosed with WFS based on genetic testing in 2008-2011 were analyzed. The average age of the patients at diabetes onset was 5 (4.4-6.3) years, and the mean HbA1c level at diagnosis was 9.1±2.3%. Initially, all of these patients were treated as having type 1 diabetes with progressive visual impairment despite good metabolic control (mean HbA1c 7.5±1.3%). Diagnosis of optic atrophy was made at an average age of 9 (5.9-11.5) years, which corresponds to 4 years after diabetes recognition (p=0.002). At the time of genetic analysis, the average age of the patients was 16 (12-18.7) years, which corresponds to 7 years after recognition of coexistence of diabetes mellitus and optic atrophy (p=0.007). Delays of at least 7 years occurred before recognition of WFS among a cohort of pediatric patients with diabetes. All patients with WFS were primarily misdiagnosed as having type 1 diabetes. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.
García Castaño, Alejandro; Pérez de Nanclares, Gustavo; Madariaga, Leire; Aguirre, Mireia; Madrid, Alvaro; Nadal, Inmaculada; Navarro, Mercedes; Lucas, Elena; Fijo, Julia; Espino, Mar; Espitaletta, Zilac; Castaño, Luis; Ariceta, Gema
The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.
Alejandro García Castaño
Full Text Available The p.Ala204Thr mutation (exon 7 of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families were homozygous (57.7% of overall patients. Another 8 patients (5 families were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings presented with the c. -19-?_2053+? del deletion (comprising the entire gene; one patient carried the p.Val170Met mutation (exon 6; and 4 patients (3 siblings presented with the novel p.Glu442Gly mutation (exon 14. On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12 associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16 as well as the already described p.Ala210Val change (exon 7. One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.
Steca, Patrizia; D’Addario, Marco; Magrin, Maria Elena; Miglioretti, Massimo; Monzani, Dario; Pancani, Luca; Sarini, Marcello; Scrignaro, Marta; Vecchio, Luca; Fattirolli, Francesco; Giannattasio, Cristina; Cesana, Francesca; Riccobono, Salvatore Pio
Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs), but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men). Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed. PMID:27589065
Full Text Available Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs, but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men. Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed.
Ezz El-Arab, A.; El Fouly, A.H.; Mahmoud, H.H.
There is accumulating evidence determine that the metabolism of some trace elements is altered in diabetes mellitus (DM) type II. The current study aimed to evaluate the effect of serum blood glucose fluctuation during (Random, Fasting and Postprandial 2 hours state) on some trace elements such as Cadmium (Cd), Chromium (Cr), Manganese (Mn), Magnesium (Mg), Zinc (Zn), Copper (Cu), Sodium (Na), Potassium (K), and Aldosterone hormone in type II Diabetic patients associated with metabolic syndrome in comparison with healthy volunteers. The International Diabetes Federation (IFD) consensus the diagnosis of metabolic syndrome according to central obesity, lipid profile, blood glucose level and blood pressure. A significant change was observed in trace elements level (Cd, Cr, Mg, Mn, Zn, Cu, Na, and K) and Aldosterone hormone as a result of glucose fluctuation among type II diabetic patients.
Full Text Available Introduction & Objective: Polycystic ovary syndrome (PCOS is a heterogeneous disorder that affects 5-10% of women of reproductive age patients with this syndrome one of the high risk groups for type 2 diabetes mellitus in future. This study was carried out to determine the prevalence of PCOS in patients with type 2 diabetes mellitus. Materials & Methods: One hundred women under 45 years with type 2 diabetes treating with diet or hypoglycemic drugs, referred to Kerman diabetic center in 2005 were identified. Women with galactorrhea or history of thyroid dysfunction were excluded from the study. Data were collected through interview and then data of 92 women were analyzed using t-test and x2. Results: Ninety two women enrolled in the study and 18 cases (19.5% had clinical symptoms of PCOS. The mean of age was 38 years (38.76±5.92 years. The mean age of women with PCOS was 34.89±3.96 and that of normal women was 39.7±5.96 years (P0.05. Conclusion: This study indicated women with type 2 diabetes mellitus had a higher prevalence of polycystic syndrome. Android obesity is associated with the increased risk of type 2 diabetes in women with PCOS.
Full Text Available Introduction & Objective: Polycystic ovary syndrome (PCOS is a heterogeneous disorder that affects 5-10% of women of reproductive age patients with this syndrome one of the high risk groups for type 2 diabetes mellitus in future. This study was carried out to determine the prevalence of PCOS in patients with type 2 diabetes mellitus. Materials & Methods: One hundred women under 45 years with type 2 diabetes treating with diet or hypoglycemic drugs, referred to Kerman diabetic center in 2005 were identified. Women with galactorrhea or history of thyroid dysfunction were excluded from the study. Data were collected through interview and then data of 92 women were analyzed using t-test and x2. Results: Ninety two women enrolled in the study and 18 cases (19.5% had clinical symptoms of PCOS. The mean of age was 38 years (38.76±5.92 years. The mean age of women with PCOS was 34 and that of normal women was 39 years (P0.05. Conclusion: This study indicated women with type 2 diabetes mellitus had a higher prevalence of polycystic syndrome. Android obesity is associated with the increased risk of type 2 diabetes in women with PCOS.
Inamura, Shunichi; Furuya, Hidekazu; Yagi, Kentarou; Ikeya, Eriko; Yamaguchi, Masaomi; Fujimura, Takabumi; Kanabuchi, Kazuo
To reconstruct the aortic root for aneurysm of the ascending aorta accompanied by aortic regurgitation, annuloaortic ectasia (AAE) and acute type-A dissection with root destruction, the Bentall operation using a prosthetic valve still is the standard procedure today. Valve-sparing procedures have actively been used for aortic root lesions, and have also been attempted in aortic root reconstruction for Marfan syndrome which may have abnormalities in the valve leaflets. We conducted a valve-sparing procedure in a female patient with Marfan syndrome who had AAE accompanied by type-A acute aortic dissection. The patient was a 37-year-old woman complaining of severe pain from the chest to the back. The limbs were long, and funnel breast was observed. Diastolic murmurs were heard. On chest computed tomography, a dissection cavity was present from the ascending aorta to the left common iliac artery, and the root dilated to 55 mm. Grade II aortic regurgitation was observed on ultrasound cardiography. Regarding her family history, her father had died suddenly at 54 years of age. She was diagnosed with type-A acute dissection concurrent with Marfan syndrome and AAE. The structure of the aortic valve was normal, and root reconstruction by a valve-sparing operation and total replacement of the aortic arch was conducted. On postoperative ultrasound cardiography, the aortic regurgitation was within the allowable range, and the shortterm postoperative results were good.
Maraj, Hemant; Mohajer, Michelle; Bhattacharjee, Deepannita
We present the case of a 31-year-old woman with Ehler-Danlos syndrome (EDS) type 2. She had a previous caesarean section and went on to have an uncomplicated vaginal birth in her last pregnancy. To our knowledge, this is the first case of a successful vaginal birth after caesarean section in a patient with EDS. EDS is a multisystem disorder involving a genetic defect in collagen and connective-tissue synthesis and structure. It is a heterogeneous group of 11 different inherited disorders. Obstetric complications in these patients include miscarriages, stillbirths, premature rupture of the membranes, preterm labour, uterine prolapse, uterine rupture and severe postpartum haemorrhage. There has been much controversy over the appropriate mode of delivery. Abdominal deliveries are complicated by delayed wound healing and increased perioperative blood loss. Vaginal deliveries may be complicated by tissue friability causing extensive perineal tears, pelvic floor and bladder lesions. Our case highlights that in specific, controlled situations it is possible to have a vaginal delivery even after previous caesarean section in patients with EDS.
Das, Mithun; Pal, Susil; Ghosh, Arnab
Our objective was to test the association between familial risk of type 2 diabetes mellitus (T2DM) and the prevalence of metabolic syndrome (MS) in adult Asian Indians. A total of 448 adult (>30 years) individuals (257 males and 191 females) participated in the study. Familial risk of T2DM was classified into three groups viz., 1=both parents affected; 2=parent and/or siblings affected and 3=none or no family history for T2DM. Anthropometric measures, blood pressures, fasting blood glucose and metabolic profiles were studied using standard techniques. MS was defined accordingly. The prevalence of MS phenotypes was estimated and compared among the three familial risk strata. Individuals with a history of both parents affected from diabetes had significantly higher (Pfamily history of T2DM. Significant difference was also noticed between individuals with and without MS according to the family history of diabetes (Pfamily history of T2DM. Family history of T2DM had significant effect on individuals with MS as compared to their counterparts (individuals having no family history of T2DM). It therefore seems reasonable to argue that family history of T2DM could be useful as a predictive tool for early diagnosis and prevention of MS in Asian Indian population.
Full Text Available Waardenburg syndrome (WS is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2 can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.
Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege
Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy. PMID:22848661
Yang, Shuzhi; Dai, Pu; Liu, Xin; Kang, Dongyang; Zhang, Xin; Yang, Weiyan; Zhou, Chengyong; Yang, Shiming; Yuan, Huijun
Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.
Full Text Available Waardenburg Syndrome (WS is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF gene mutations account for about 15% of WS type II (WS2 cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0% and heterochromia iridum (20/20, 100.0% were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0% had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14, which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients.
Sólia-Nasser, L; de Aquino, S-N; Paranaíba, L-M R; Gomes, A; Dos-Santos-Neto, P; Coletta, R-D; Cardoso, A-F; Frota, A-C; Martelli-Júnior, H
The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.
Bai, Y; Liu, N; Kong, X D; Yan, J; Qin, Z B; Wang, B
Objective: To analyze the mutations of PAX3 gene in two Waardenburg syndrome type Ⅰ (WS1) pedigrees and make prenatal diagnosis for the high-risk 18-week-old fetus. Methods: PAX3 gene was first analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) for detecting pathogenic mutation of the probands of the two pedigrees. The mutations were confirmed by MLPA and Sanger in parents and unrelated healthy individuals.Prenatal genetic diagnosis for the high-risk fetus was performed by amniotic fluid cell after genotyping. Results: A heterozygous PAX3 gene gross deletion (E7 deletion) was identified in all patients from WS1-01 family, and not found in 20 healthy individuals.Prenatal diagnosis in WS1-01 family indicated that the fetus was normal. Molecular studies identified a novel deletion mutation c. 1385_1386delCT within the PAX3 gene in all affected WS1-02 family members, but in none of the unaffected relatives and 200 healthy individuals. Conclusions: PAX3 gene mutation is etiological for two WS1 families. Sanger sequencing plus MLPA is effective and accurate for making gene diagnosis and prenatal diagnosis.
Martínez Cerón, Elisabet; Casitas Mateos, Raquel; García-Río, Francisco
Epidemiological data suggest that sleep apnea-hypopnea syndrome (SAHS) is independently associated with the development of insulin resistance and glucose intolerance. Moreover, despite significant methodological limitations, some studies report a high prevalence of SAHS in patients with type 2 diabetes mellitus (DM2). A recent meta-analysis shows that moderate-severe SAHS is associated with an increased risk of DM2 (relative risk=1.63 [1.09 to 2.45]), compared to the absence of apneas and hypopneas. Common alterations in various pathogenic pathways add biological plausibility to this relationship. Intermittent hypoxia and sleep fragmentation, caused by successive apnea-hypopnea episodes, induce several intermediate disorders, such as activation of the sympathetic nervous system, oxidative stress, systemic inflammation, alterations in appetite-regulating hormones and activation of the hypothalamic-pituitary-adrenal axis which, in turn, favor the development of insulin resistance, its progression to glucose intolerance and, ultimately, to DM2. Concomitant SAHS seems to increase DM2 severity, since it worsens glycemic control and enhances the effects of atherosclerosis on the development of macrovascular complications. Furthermore, SAHS may be associated with the development of microvascular complications: retinopathy, nephropathy or diabetic neuropathy in particular. Data are still scant, but it seems that DM2 may also worsen SAHS progression, by increasing the collapsibility of the upper airway and the development of central apneas and hypopneas. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.
Full Text Available The hepatopulmonary syndrome (HPS develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2 play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL. We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064 induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.
Wimmer, K; Rosenbaum, T; Messiaen, L
Constitutional mismatch repair (MMR) deficiency (CMMRD) is a rare childhood cancer susceptibility syndrome resulting from biallelic germline loss-of-function mutations in one of the MMR genes. Individuals with CMMRD have high risk to develop a broad spectrum of malignancies and frequently display features reminiscent of neurofibromatosis type 1 (NF1). Evaluation of the clinical findings of genetically proven CMMRD patients shows that not only multiple café-au-lait macules but also any of the diagnostic features of NF1 may be present in a CMMRD patient. This phenotypic overlap may lead to misdiagnosis of CMMRD patients as having NF1, which impedes adequate management of the patients and their families. The spectrum of CMMRD-associated childhood malignancies includes high-grade glioma, acute myeloid leukaemia or rhabdomyosarcoma, also reported as associated with NF1. Reported associations between NF1 and these malignancies are to a large extent based on studies that neither proved the presence of an NF1 germline mutation nor ruled-out CMMRD in the affected. Hence, these associations are challenged by our current knowledge of the phenotypic overlap between NF1 and CMMRD and should be re-evaluated in future studies. Recent advances in the diagnostics of CMMRD should render it possible to definitely state or refute this diagnosis in these individuals. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Tang, Chaoliang; Li, Juan; Tai, Wai Lydia; Yao, Weifeng; Zhao, Bo; Hong, Junmou; Shi, Si; Wang, Song; Xia, Zhongyuan
Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I. Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines. Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion. Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.
Yang, Shuzhi; Dai, Pu; Liu, Xin; Kang, Dongyang; Zhang, Xin; Yang, Weiyan; Zhou, Chengyong; Yang, Shiming; Yuan, Huijun
Waardenburg Syndrome (WS) is an autosomal-dominant disorder characterized by sensorineural hearing loss and pigmentary abnormalities of the eyes, hair, and skin. Microphthalmia-associated transcription factor (MITF) gene mutations account for about 15% of WS type II (WS2) cases. To date, fewer than 40 different MITF gene mutations have been identified in human WS2 patients, and few of these were of Chinese descent. In this study, we report clinical findings and mutation identification in the MITF gene of 20 Chinese WS2 patients from 14 families. A high level of clinical variability was identified. Sensorineural hearing loss (17/20, 85.0%) and heterochromia iridum (20/20, 100.0%) were the most commonly observed clinical features in Chinese WS2 patients. Five affected individuals (5/20, 25.0%) had numerous brown freckles on the face, trunk, and limb extremities. Mutation screening of the MITF gene identified five mutations: c.20A>G, c.332C>T, c.647_649delGAA, c.649A>G, and c.763C>T. The total mutational frequency of the MITF gene was 21.4% (3/14), which is significantly higher than the 15.0% observed in the fair-skinned WS2 population. Our results indicate that MITF mutations are relatively common among Chinese WS2 patients. PMID:24194866
Morell, R; Spritz, R A; Ho, L; Pierpont, J; Guo, W; Friedman, T B; Asher, J H
Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease accounting for >2% of the congenitally deaf population. It is characterized by deafness in association with pigmentary anomalies and various defects of neural crest-derived tissues. At least four types are recognized (WS1, WS2, WS3 and WS4) on the basis of clinical and genetic criteria. Two previously described families seemed to delineate a new subtype characterized by WS2 in conjunction with ocular albinism (OA). Since mutations in the MITF gene are responsible for some instances of WS2, we screened for mutations in one of the WS2-OA families and discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated with compound heterozygosity for a mutant TYR allele and the TYR(R402Q) allele, a functionally significant polymorphism that is associated with moderately reduced tyrosinase catalytic activity. In this family, all of the individuals with the OA phenotype are either homozygous or heterozygous for TYR(R402Q), and heterozyous for the 1 bp deletion in MITF This suggests that the WS2-OA phenotype may result from digenic interaction between a gene for a transcription factor (MITF) and a gene that it regulates (TYR).
Kaiserman, Nadia; Obolensky, Alexey; Banin, Eyal; Sharon, Dror
To identify USH2A mutations in Israeli patients with autosomal-recessive Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP). Patients from 95 families with RP and 4 with USH2 were clinically evaluated. USH2A exons 2-72 were scanned for mutations using single-strand conformation and sequencing analyses. The frequency of novel missense changes was determined in patients and controls using restriction endonucleases. The analysis revealed 3 USH2A mutations, 2 of which are novel, in 2 families with USH2 and a large family (MOL0051) with both USH2 and RP. Compound heterozygotes for 2 null mutations (Thr80fs and Arg737stop) in MOL0051 suffered from USH2 while compound heterozygotes for 1 of the null mutations and a novel missense mutation (Gly4674Arg) had nonsyndromic RP. Our results support the involvement of USH2A in nonsyndromic RP and we report here of a second, novel, missense mutation in this gene causing autosomal-recessive RP. Possible involvement of USH2A should be considered in the molecular genetic evaluation of patients with autosomal-recessive RP. Understanding the mechanism by which different USH2A mutations cause either USH2 or RP may assist in the development of novel therapeutic approaches.
Joensuu, T; Hämäläinen, R; Yuan, B; Johnson, C; Tegelberg, S; Gasparini, P; Zelante, L; Pirvola, U; Pakarinen, L; Lehesjoki, A E; de la Chapelle, A; Sankila, E M
Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterized by progressive hearing loss, severe retinal degeneration, and variably present vestibular dysfunction, assigned to 3q21-q25. Here, we report on the positional cloning of the USH3 gene. By haplotype and linkage-disequilibrium analyses in Finnish carriers of a putative founder mutation, the critical region was narrowed to 250 kb, of which we sequenced, assembled, and annotated 207 kb. Two novel genes-NOPAR and UCRP-and one previously identified gene-H963-were excluded as USH3, on the basis of mutational analysis. USH3, the candidate gene that we identified, encodes a 120-amino-acid protein. Fifty-two Finnish patients were homozygous for a termination mutation, Y100X; patients in two Finnish families were compound heterozygous for Y100X and for a missense mutation, M44K, whereas patients in an Italian family were homozygous for a 3-bp deletion leading to an amino acid deletion and substitution. USH3 has two predicted transmembrane domains, and it shows no homology to known genes. As revealed by northern blotting and reverse-transcriptase PCR, it is expressed in many tissues, including the retina.
Full Text Available Autoimmune polyendocrine syndrome type 1 (APS-1 is a rare autosomal recessive disease defined by the presence of two of the three conditions: mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease. Loss-of-function mutations of the autoimmune regulator (AIRE gene have been linked to APS-1. Here we report mutational analysis and functional characterization of an AIRE mutation in a consanguineous Chinese family with APS-1. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. We identified a homozygous missense AIRE mutation c.463G>A (p.Gly155Ser in two siblings with different clinical features of APS-1. In silico splice-site prediction and minigene analysis were carried out to study the potential pathological consequence. Minigene splicing analysis and subsequent cDNA sequencing revealed that the AIRE mutation potentially compromised the recognition of the splice donor of intron 3, causing alternative pre-mRNA splicing by intron 3 retention. Furthermore, the aberrant AIRE transcript was identified in a heterozygous carrier of the c.463G>A mutation. The aberrant intron 3-retaining transcript generated a truncated protein (p.G155fsX203 containing the first 154 AIRE amino acids and followed by 48 aberrant amino acids. Therefore, our study represents the first functional characterization of the alternatively spliced AIRE mutation that may explain the pathogenetic role in APS-1.
Ye, Ying; Zhong, Wenling; Lin, Xiuquan; Lin, Shuguang; Lin, Xi; Li, Xiaoqing; Chen, Tiehui
To explore the association of sedentary life style with risk of metabolic syndrome (MS) and diabetes mellitus type 2(T2DM). A total of 6 016 local residents aged 18 years or older in Fujian province were recruited by multi-stage stratified cluster sampling method in 2010-2011. Data, including demographic information, physical activity and sedentary time were collected. Indices related to height, weight, waist circumference, blood pressure and blood lipid were determined while MS and T2DM were diagnosed by IDF (2005) and WHO (1999) criteria. Logistic regression was used to estimate the correlations between sedentary behavior and MS or T2DM. The prevalence rates of MS and T2DM were 19.0% and 8.0% respectively, in local residents aged 18 years or older, in Fujian province. The overall rate of sedentary behavior was 18.1%, with the mean sedentary time as 4.3 hours. Both data showed significantly differences (P sedentary time sedentary behavior was independently associated with an increased risk of MT group (OR = 1.82, 95% CI: 1.33-2.48, P sedentary behavior/sedentary time. MS and T2DM were associated with sedentary lifestyle, but these findings should be confirmed through further longitudinal studies.
Ehn, Mattias; Wahlqvist, Moa; Danermark, Berth; Dahlström, Örjan; Möller, Claes
Research has demonstrated that persons with Usher syndrome type 1 (USH1) have significantly poorer physical and psychological health compared to a reference group. To explore the relation between work, health, social trust, and financial situation in USH1 compared to a reference group. Sixty-six persons (18-65 y) from the Swedish Usher database received a questionnaire and 47 were included, 23 working and 24 non-working. The reference group comprised 3,049 working and 198 non-working persons. The Swedish Health on Equal Terms questionnaire was used and statistical analysis with multiple logistic regression was conducted. The USH1 non-work group had a higher Odds ratio (95% CI) in poor psychological and physical health, social trust, and financial situation compared to the USH1 work group and reference groups. Age, gender, hearing, and vision impairment did not explain the differences. The relation between the USH1 work and non-work groups showed the same pattern as the reference groups, but the magnitude of problems was significantly higher. Both disability and unemployment increased the risk of poor health, social trust and financial situation in persons with USH1, but having an employment seemed to counteract the risks related to disability.
Möller, Kerstin; Eriksson, Kristina; Sadeghi, André M; Möller, Claes; Danermark, Berth
The aim was to explore ophthalmic health care in female patients with Usher Syndrome type I (USH I) over 20 years and to evaluate the relationship between the ophthalmic health care and the health state of the patients from a health perspective. A retrospective study of records from ophthalmology departments (OD) and low vision clinics (LVC) from 1985 to 2004. Assessment of the reports was performed based on the International Classification of Functioning, Disability and Health (ICF). Findings were analysed by manifest content analysis with ICF as a framework and using four themes: health care system, procedure examinations, patient's functioning and disability and procedure actions. The records of nine female patients (aged 25-39 years, 1985) with USH I were selected from the national database of USH. A great number of notes were collected (OD 344 and LVC 566). Procedure examinations were exclusively oriented towards body structure and function. All patients showed aggravated visual impairment over and above the hearing and vestibular impairment. Procedure actions were oriented towards environmental factors. No correlation was found between procedures performed and patient's experience of disability. The high degree of resource allocation was not correlated to the patients' impairment. The study indicates that the ophthalmic health care was characterised by inefficiency. This conclusion is very serious because patients very likely face severe disability and emotional difficulties. ICF is ought to be incorporated in ophthalmic health care strategy to improve the health care.
Hamatani, Mio; Jingami, Naoto; Uemura, Kengo; Nakasone, Naoe; Kinoshita, Hisanori; Yamakado, Hodaka; Ninomiya, Haruaki; Takahashi, Ryosuke
A 40-year-old man was referred to our hospital because of vertical supranuclear gaze palsy, frequent sudden loss of muscle tonus and ataxia for several years. He had a history of prolonged neonatal jaundice. He was given a diagnosis of autism in his childhood, followed by a diagnosis of schizophrenia in his teenage. He also developed a savant skill of calendar calculating. (123)I-IMP-SPECT showed decreased cerebral blood flow in the left frontotemporal lobe as often seen in savant syndrome. Although genetic analysis of NPC1 and NPC2 revealed no pathogenic mutation, filipin staining of cultured fibroblasts from his biopsied skin revealed a certain amount of intracellular cholesterol storage pattern, indicating a variant biochemical phenotype of Niemann-Pick disease type C (NPC). The diagnosis of adulthood onset NPC is difficult and challenging, especially for neurologists, because the symptoms and signs are not as clear as those in the classical childhood onset NPC and this subtype is not yet widely known. However, the diagnosis can be made by a combination of filipin staining of fibroblast and/or gene analysis. As a disease-specific therapy for NPC has been approved in Japan, the diagnosis of NPC is of significance.
Cheng, Ling; Yu, Hongsong; Jiang, Yan; He, Juan; Pu, Sisi; Li, Xin; Zhang, Li
Usher syndrome (USH) is an autosomal recessive disease characterized by deafness and retinitis pigmentosa. In view of the high phenotypic and genetic heterogeneity in USH, performing genetic screening with traditional methods is impractical. In the present study, we carried out targeted next-generation sequencing (NGS) to uncover the underlying gene in an USH family (2 USH patients and 15 unaffected relatives). One hundred and thirty-five genes associated with inherited retinal degeneration were selected for deep exome sequencing. Subsequently, variant analysis, Sanger validation and segregation tests were utilized to identify the disease-causing mutations in this family. All affected individuals had a classic USH type I (USH1) phenotype which included deafness, vestibular dysfunction and retinitis pigmentosa. Targeted NGS and Sanger sequencing validation suggested that USH1 patients carried an unreported splice site mutation, c.5168+1G>A, as a compound heterozygous mutation with c.6070C>T (p.R2024X) in the MYO7A gene. A functional study revealed decreased expression of the MYO7A gene in the individuals carrying heterozygous mutations. In conclusion, targeted next-generation sequencing provided a comprehensive and efficient diagnosis for USH1. This study revealed the genetic defects in the MYO7A gene and expanded the spectrum of clinical phenotypes associated with USH1 mutations.
Schietroma, Cataldo; Parain, Karine; Estivalet, Amrit; Aghaie, Asadollah; Boutet de Monvel, Jacques; Picaud, Serge; Sahel, José-Alain; Perron, Muriel; El-Amraoui, Aziz; Petit, Christine
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis , these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23 , encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15-containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. © 2017 Schietroma et al.
Parain, Karine; Aghaie, Asadollah; Picaud, Serge
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. PMID:28495838
Hartel, Bas P; van Nierop, Josephine W I; Huinck, Wendy J; Rotteveel, Liselotte J C; Mylanus, Emmanuel A M; Snik, Ad F; Kunst, Henricus P M; Pennings, Ronald J E
Usher syndrome type IIa (USH2a) is characterized by congenital moderate to severe hearing impairment and retinitis pigmentosa. Hearing rehabilitation starts in early childhood with the application of hearing aids. In some patients with USH2a, severe progression of hearing impairment leads to insufficient speech intelligibility with hearing aids and issues with adequate communication and safety. Cochlear implantation (CI) is the next step in rehabilitation of such patients. This study evaluates the performance and benefit of CI in patients with USH2a. Retrospective case-control study to evaluate the performance and benefit of CI in 16 postlingually deaf adults (eight patients with USH2a and eight matched controls). Performance and benefit were evaluated by a speech intelligibility test and three quality-of-life questionnaires. Patients with USH2a with a mean age of 59 years at implantation exhibited good performance after CI. The phoneme scores improved significantly from 41 to 87% in patients with USH2a (p = 0.02) and from 30 to 86% in the control group (p = 0.001). The results of the questionnaire survey demonstrated a clear benefit from CI. There were no differences in performance or benefit between patients with USH2a and control patients before and after CI. CI increases speech intelligibility and improves quality of life in patients with USH2a.
Krarup, Therese; Krarup, Thure; Hagen, Claus
increased production of cortisol and thus represent patients with CS. The aim of this review was to evaluate the prevalence of CS in patients with T2DM. A search was performed in PubMed and Medline. We found seven prospective studies, two case-control studies and two cross-sectional studies......Many clinical features are common for patients with type 2 diabetes mellitus (T2DM) and Cushing's syndrome (CS) such as central obesity, hypertension and dyslipidaemia. Patients with CS often have T2DM. Because T2DM is much more frequent than CS, it is possible that some patients with T2DM have...... with T2DM varies widely between the different studies, ranging from 0-9.4%. This may be due to patient selection, differences in test methodology (including choice of test), cutoff values and different cortisol assays. The true prevalence of CS in T2DM has not been determined. We need more studies...
Saxena, R; Welt, C K
Polycystic ovary syndrome (PCOS) is a disorder of irregular menses, hyperandrogenism and/or polycystic ovary morphology. A large proportion of women with PCOS also exhibit insulin resistance, β-cell dysfunction, impaired glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that genetic variants that predispose to risk of T2D also result in risk of PCOS. Variants robustly associated with T2D in candidate gene or genome-wide association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years. Metabolic, reproductive and anthropomorphic data were examined as a function of the T2D variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. There was a nominal association between variants in KCNJ11 and risk of PCOS. However, a risk score of 33 independent T2D-associated variants from GWAS was not significantly associated with PCOS. T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes risk variants are not important risk variants for PCOS.
Joan C. Lo
Full Text Available Background. This study examines gestational diabetes mellitus (GDM in women with polycystic ovary syndrome (PCOS and the risk of type 2 diabetes mellitus (DM following GDM pregnancy. Methods. A cohort of 988 pregnant women with PCOS who delivered during 2002–2005 was examined to determine the prevalence and predictors of GDM, with follow-up through 2010 among those with GDM to estimate the risk of DM. Results. Of the 988 pregnant women with PCOS, 192 (19% developed GDM. Multivariable predictors of GDM included older age, Asian race, prepregnancy obesity, family history of DM, preconception metformin use, and multiple gestation. Among women with PCOS and GDM pregnancy, the incidence of DM was 2.8 (95% confidence interval (CI 1.9–4.2 per 100 person-years and substantially higher for those who received pharmacologic treatment for GDM (6.6 versus 1.5 per 100 person-years, p<0.01. The multivariable adjusted risk of DM was fourfold higher in women who received pharmacologic treatment for GDM (adjusted hazard ratio 4.1, 95% CI 1.8–9.6. The five-year incidence of DM was 13.1% overall and also higher in the pharmacologic treatment subgroup (27.0% versus 7.1%, p<0.01. Conclusions. The strongest predictors of GDM among women with PCOS included Asian race and prepregnancy obesity. Pharmacologic treatment of GDM is associated with fourfold higher risk of subsequent DM.
Matsunaga, Tatsuo; Mutai, Hideki; Namba, Kazunori; Morita, Noriko; Masuda, Sawako
PAX3 genetic analysis increased the diagnostic accuracy for Waardenburg syndrome type I (WS1). Analysis of the three-dimensional (3D) structure of PAX3 helped verify the pathogenicity of a missense mutation, and multiple ligation-dependent probe amplification (MLPA) analysis of PAX3 increased the sensitivity of genetic diagnosis in patients with WS1. Clinical diagnosis of WS1 is often difficult in individual patients with isolated, mild, or non-specific symptoms. The objective of the present study was to facilitate the accurate diagnosis of WS1 through genetic analysis of PAX3 and to expand the spectrum of known PAX3 mutations. In two Japanese families with WS1, we conducted a clinical evaluation of symptoms and genetic analysis, which involved direct sequencing, MLPA analysis, quantitative PCR of PAX3, and analysis of the predicted 3D structure of PAX3. The normal-hearing control group comprised 92 subjects who had normal hearing according to pure tone audiometry. In one family, direct sequencing of PAX3 identified a heterozygous mutation, p.I59F. Analysis of PAX3 3D structures indicated that this mutation distorted the DNA-binding site of PAX3. In the other family, MLPA analysis and subsequent quantitative PCR detected a large, heterozygous deletion spanning 1759-2554 kb that eliminated 12-18 genes including a whole PAX3 gene.
Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege
Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.
Diep, D; Fau, V; Wdowik, S; Bienvenu, B; Bénateau, H; Veyssière, A
The Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is a rare genetic disease. Diagnosis is based on a combination of clinical criteria described in the classification of Villefranche. Diagnosis is difficult to make because of the lack of specific clinical signs and the absence of genetic testing. The EDS-TH manifests itself manly by musculoskeletal pain and joint hypermobility. Temporomandibular disorders (TMD) are also reported. Our aim was to objectify the presence and to qualify the type of TMD associated with the EDS-HT in order to propose an additional diagnostic argument. A prospective, monocenter case-control study, comparing a cohort of patients suffering from EDS-HT to a paired control group of healthy volunteers has been conducted. Clinical examination was standardized, including a general questioning, an oral examination and a temporomandibular joint examination following the TMD/RDC (temporomandibular disorders/research diagnostic criteria). Fourteen EDS-HT patients and 58 control patients were examined. The prevalence of TMDs (n=13; 92.9% vs. n=4; 6.9%; P=10(-11)) was significantly higher in the EDS-HT group. TMDs occurring in the EDS-HT group were complex, combining several mechanisms in contrast to the control group, where only one mechanism was found in all the patients (n=13; 92.9% vs. n=0; 0.0%). TMDs are strongly associated with RDS-HT. TMDs could therefore be used in the diagnosis of this disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Bruserud, Øyvind; Oftedal, Bergithe E.; Landegren, Nils; Erichsen, Martina M.; Bratland, Eirik; Lima, Kari; Jørgensen, Anders P.; Myhre, Anne G.; Svartberg, Johan; Fougner, Kristian J.; Bakke, Åsne; Nedrebø, Bjørn G.; Mella, Bjarne; Breivik, Lars; Viken, Marte K.; Knappskog, Per M.; Marthinussen, Mihaela C.; Løvås, Kristian; Kämpe, Olle; Wolff, Anette B.
Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996–2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-ω) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-ω) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center. PMID:27253668
Yang, Shu-Zhi; Cao, Ju-Yang; Zhang, Rui-Ning; Liu, Li-Xian; Liu, Xin; Zhang, Xin; Kang, Dong-Yang; Li, Mei; Han, Dong-Yi; Yuan, Hui-Jun; Yang, Wei-Yan
Waardenburg syndrome type I (WS1) is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmental abnormalities of the eye, hair and skin, and dystopia canthorum. The gene mainly responsible for WS1 is PAX3 which is involved in melanocytic development and survival. Mutations of PAX3 have been reported in familiar or sporadic patients with WS1 in several populations of the world except Chinese. In order to explore the genetic background of Chinese WS1 patients, a mutation screening of PAX3 gene was carried out in four WS1 pedigrees. A questionnaire survey and comprehensive clinical examination were conducted in four Chinese pedigrees of WS1. Genomic DNA from each patient and their family members was extracted and exons of PAX3 were amplified by PCR. PCR fragments were ethanol-purified and sequenced in both directions on an ABI_Prism 3100 DNA sequencer with the BigDye Terminator Cycle Sequencing Ready Reaction Kit. The sequences were obtained and aligned to the wild type sequence of PAX3 with the GeneTool program. Two nonsense PAX3 mutations have been found in the study population. One is heterozygous for a novel nonsense mutation S209X. The other is heterozygous for a previously reported mutation in European population R223X. Both mutations create stop codons leading to truncation of the PAX3 protein. This is the first demonstration of PAX3 mutations in Chinese WS1 patients and one of the few examples of an identical mutation of PAX3 occurred in different populations.
Bialocerkowski, Andrea E; Daly, Anne
This study synthesized current research evidence on the effectiveness of physiotherapy for the management of children diagnosed with complex regional pain syndrome type 1 (CRPS-1), to provide up-to-date physiotherapy treatment recommendations, and to identify areas that require further investigation. Nine electronic databases were searched for quantitative studies that evaluated the effect of physiotherapy on children with CRPS-1. The methodological quality of the studies was evaluated using the Critical Review Form. Data were extracted regarding the study design, participant characteristics, types of outcome measures used, and physiotherapy technique used and its effectiveness. The search strategy identified 303 potential studies, of which 12 met the inclusion criteria (1 randomized controlled trial, 1 comparative study, 10 case series). The methodological quality of all studies was rated as poor to fair. The "stand-alone" value of physiotherapy could not be determined as physiotherapy was prescribed in conjunction with psychological and medical interventions. There is low volume and poor-to-fair quality evidence which suggests that physiotherapy prescribed with other interventions may lead to short-term improvement in the signs and symptoms of CRPS-1 or functional ability in children with CRPS-1, and the relapse rate may be moderately high. High-quality studies are required in this area. These studies should evaluate a package of care (which includes physiotherapy); they should investigate the effects of physiotherapy treatments that have proven effectiveness in adults with CRPS-1; they should use psychometrically sound measures to evaluate outcome; and the nature of physiotherapy should be detailed in future publications to enable replication in the clinical setting.
Duquesnoy, P; Sobrier, M L; Amselem, S; Goossens, M
Mutations in the growth hormone receptor (GHR) gene can cause growth hormone (GH) resistance. Given the sequence homology between the extracellular domain of the GHR and a soluble GH-binding protein (GH-BP), it is remarkable that GH-BP binding activity is absent from the serum of patients with Laron-type GH insensitivity, a hereditary form of severe dwarfism. We have previously identified a mutation within the extracellular domain of this receptor, replacing phenylalanine by serine at position 96 of the mature protein, in a patient with Laron syndrome. We have now investigated the effect of this Phe----Ser substitution on hormone binding activity by expressing the total human GHR cDNA and mutant form in eukaryotic cells. The wild-type protein expressed was able to bind GH but no plasma membrane binding was detectable on cells transfected with the mutant cDNA; this was also the case of cells transfected with a Phe96----Ala mutant cDNA, suggesting that the lack of binding activity is not due to a posttranslational modification of serine. Examination of the variant proteins in subcellular fractions revealed the presence of specific GH binding activity in the lysosomal fraction, whereas immunofluorescence studies located mutant proteins in the cytosol. Our findings suggest that these mutant GHRs fail to follow the correct intracellular transport pathway and underline the potential importance of this phenylalanine residue, which is conserved among the GH, prolactin, and erythropoietin receptors that belong to the same cytokine receptor superfamily. Images PMID:1719554
Ruotsalainen, Hanna K; Pihkala, Jaana; Salminen, Jukka; Hornberger, Lisa K; Sairanen, Heikki; Ojala, Tiina
We investigated the impact of initial shunt type, a Blalock-Taussig (BT) shunt versus a right ventricle to pulmonary artery conduit (RV-PA) on myocardial function at different stages of surgical palliation in patients with hypoplastic left heart syndrome (HLHS). A population-based cohort of 63 Finnish children with HLHS (BT n = 23, RV-PA n = 40) born between 2003 and 2010 were studied retrospectively by echocardiography prior to Stages 1, 2 and 3 palliation and 0.5-3 years after Stage 3. For comparison of systolic myocardial function, we evaluated the RV fractional area change (FAC), strain, strain rate and mechanical synchrony from the apical 4-chamber view by velocity vector imaging. There were no intergroup differences in demographics during the study period. At baseline, no intergroup differences were detected in RV systolic myocardial function. Before Stage 2, RV FAC was higher ( P = 0.03) in the RV-PA conduit group. At Stage 3, an increase in all systolic myocardial functional parameters was observed in the BT shunt group. After Stage 3, the BT shunt group had better RV systolic function. In multiple regression analysis, the shunt type and the stage of palliation had an impact on myocardial function. Although patients with HLHS initially palliated with a BT shunt demonstrate lower RV FAC after Stage I, RV FAC improves after Stage 2 with better systolic performance after Stage 3 compared with those initially palliated with an RV-PA conduit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Full Text Available Banyar Than Naing,1 Atsushi Watanabe,1,2 Shinji Tanigaki,3 Masae Ono,4 Mitsutoshi Iwashita,3 Takashi Shimada1,21Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan; 2Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan; 3Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Tokyo, Japan; 4Department of Pediatrics, Kyorin University School of Medicine, Tokyo, JapanAbstract: The vascular type of Ehlers–Danlos syndrome (EDS, EDS type IV (Online Mendelian Inheritance in Man [MIM] #130050 is characterized by thin, translucent skin, easy bruising, and arterial, intestinal, and/or uterine fragility during pregnancy, which may lead to sudden death. It is an autosomal dominant inherited disorder caused by type III procollagen gene (COL3A1: MIM #120180 mutations. Approximately 50% of the COL3A1 mutations are inherited from an affected parent, and 50% are de novo mutations. Each child of an affected individual has a 50% chance of inheriting the mutation and developing the disorder. Pregnant women with vascular EDS are at an increased risk of uterine and arterial rupture during the peripartum period, with high maternal morbidity and mortality rates. We report the first case of an asymptomatic 35-year-old woman at a risk of complications of vascular EDS who underwent presymptomatic evaluation during pregnancy. The sequencing results of both her brother and mother had a one-base-pair deletion, resulting in Glutamate at position 730 changing to Lysine and causing a frame shift and premature termination codon at 61 amino acids from the mutation position (p. Glu730Lysfs*61 on exon 32 of COL3A1. This deletion caused frameshift, leading to a premature termination codon (TAG at 181 nucleotides downstream in exon 35, which could not be detected by previous total RNA (ribonucleic acid method. Thus, she was at risk of complications of vascular EDS, and diagnostic testing was employed
... and supports a broad program of basic and clinical research on all types of epilepsy, including Dravet syndrome. Study of the genetic defects responsible for Dravet syndrome and related ... Publications Definition Dravet ...
Chandra Mohan Sharma
Full Text Available Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes , limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies.Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome,cerebellar ataxia and palatal myoclonus.This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.
López, Greizy; Gelvez, Nancy Yaneth; Tamayo, Martalucía
Usher syndrome is a disorder characterized by progressive retinitis pigmentosa, prelingual sensory hearing loss and vestibular dysfunction. It is the most frequent cause of deaf-blindness in humans. Three clinical types and twelve genetic subtypes have been characterized. Type II is the most common, and among these cases, nearly 80% have mutations in the USH2A gene. The aim of the study was to establish the mutational frequencies for the short isoform of USH2A gene in Usher syndrome type II. Twenty-six Colombian individuals with Usher syndrome type II were included. SSCP analysis for 20 exons of the short isoform was performed and abnormal patterns were sequenced. Sequencing of exon 13 of the USH2A gene was performed for all the individuals because the most frequent mutation is located in this exon. The most frequent mutation was c.2299delG, identified in the 27% (n=8) of the sample. The second mutation, p.R334W, showed a frequency of 15%. A new variant identified in the 5’UTR region, g.129G>T, was present in 1 individual (4%). Four polymorphisms were identified; one of them is a new deletion in exon 20, first reported in this study. Mutations in the usherin short isoform were identified in 38% of a sample of 26 USH2 cases. Molecular diagnosis was established in 7 of the 26.
Cvjeticanin, Miljenko; Jajić, Zrinka; Jajić, Ivo
The patterns of the ridges of the skin of the fingers and palms were determined in sixty men with complex regional pain syndrome (type I) as a measure of disease prevention. The study included 25 dermatoglyphic traits: number of epidermal ridges on all ten fingers; their sum for five and ten fingers; four traits on both palms, i.e. between a-b, b-c and c-d triradii; atd angles: and their bilateral sum. The data obtained were compared with those recorded in a control group of 200 pairs of imprints of phenotipycally healthy male adults from the Zagreb area. Statistically significant difference from control values were found in 12 dermatoglyphic variables, including an increased sum of ridges on nine fingers (except for left second finger pad), and total sum for five and ten fingers. These findings suggested the polygenic system responsible for development of dermatoglyphics to be identical with some polygenic loci for the onset of algodystrophy syndrome, which might prove useful in disease prevention (e.g., taking fingerprints following a trauma and before rehabilitation), and to facilitate identification of risk groups, and thus the treatment for this longterm and yet obscure syndrome.
Bovet, Claire; Carlson, Matthew; Taylor, Matthew
Ehlers-Danlos Syndrome, hypermobility type (EDS-HT) and the joint hypermobility syndrome (JHS) are connective tissue disorders that form an overlapping clinical syndrome and are associated with frequent medical visits and substantial morbidity. EDS-HT/JHS-associated pain correlates with poor quality of life. While physical therapy is the recommended treatment for EDS-HT/JHS, little is known about therapy-related patient experiences and iatrogenic injuries. We studied 38 adult EDS-HT/JHS patients, eliciting health-related quality of life (HRQoL) from 28 patients through the RAND SF-36 questionnaire. We also explored physical therapy experiences through focus groups with 13 patients. Our patients displayed poor HRQoL, with 71% reporting worse health over the past year. SF-36 scores were significantly lower than the scores of the average American population (P < 0.001 for 8 of 10 categories assessed), but were comparable to EDS-HT/JHS populations in Belgium, the Netherlands, Sweden, and Italy. Focus groups identified factors associated with: negative past physical therapy experiences, iatrogenic joint injuries, positive treatment experiences, and unmet rehabilitation needs. This group of EDS-HT/JHS patients has significant decrements in HRQoL and many unmet treatment needs, as well as a risk for iatrogenic injuries. We identify several approaches to help meet patients' needs and improve joint rehabilitation in patients with EDS-HT/JHS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised.
Sinibaldi, Lorenzo; Ursini, Gianluca; Castori, Marco
Psychological distress is a known feature of generalized joint hypermobility (gJHM), as well as of its most common syndromic presentation, namely Ehlers-Danlos syndrome, hypermobility type (a.k.a. joint hypermobility syndrome - JHS/EDS-HT), and significantly contributes to the quality of life of affected individuals. Most published articles dealt with the link between gJHM (or JHS/EDS-HT) and anxiety-related conditions, and a novel generation of studies is emerging aimed at investigating the psychopathologic background of such an association. In this paper, literature review was carried out with a semi-systematic approach spanning the entire spectrum of psychopathological findings in gJHM and JHS/EDS-HT. Interestingly, in addition to the confirmation of a tight link between anxiety and gJHM, preliminary connections with depression, attention deficit (and hyperactivity) disorder, autism spectrum disorders, and obsessive-compulsive personality disorder were also found. Few papers investigated the relationship with schizophrenia with contrasting results. The mind-body connections hypothesized on the basis of available data were discussed with focus on somatotype, presumed psychopathology, and involvement of the extracellular matrix in the central nervous system. The hypothesis of positive Beighton score and alteration of interoceptive/proprioceptive/body awareness as possible endophenotypes in families with symptomatic gJHM or JHS/EDS-HT is also suggested. Concluding remarks addressed the implications of the psychopathological features of gJHM and JHS/EDS-HT in clinical practice. © 2015 Wiley Periodicals, Inc.
McGee, Terri L; Seyedahmadi, Babak Jian; Sweeney, Meredith O; Dryja, Thaddeus P; Berson, Eliot L
Usher syndrome type II (USH2) is an autosomal recessive disorder characterised by retinitis pigmentosa (RP) and mild to moderate sensorineural hearing loss. Mutations in the USH2A gene are the most common cause of USH2 and are also a cause of some forms of RP without hearing loss (ie, non-syndromic RP). The USH2A gene was initially identified as a transcript comprised of 21 exons but subsequently a longer isoform containing 72 exons was identified. The 51 exons unique to the long isoform of USH2A were screened for mutations among a core set of 108 patients diagnosed with USH2 and 80 patients with non-syndromic RP who were all included in a previously reported screen of the short isoform of USH2A. For several exons, additional patients were screened. In total, 35 deleterious mutations were identified including 17 nonsense mutations, 9 frameshift mutations, 5 splice-site mutations, and 4 small in-frame deletions or insertions. Twenty-seven mutations were novel. In addition, 65 rare missense changes were identified. A method of classifying the deleterious effect of the missense changes was developed using the summed results of four different mutation assessment algorithms, SIFT, pMUT, PolyPhen, and AGVGD. This system classified 8 of the 65 changes as 'likely deleterious' and 9 as 'possibly deleterious'. At least one mutation was identified in 57-63% of USH2 cases and 19-23% of cases of non-syndromic recessive RP (calculated without and including probable/possible deleterious changes) thus supporting that USH2A is the most common known cause of RP in the USA.
Tewari, Saipriya; Madabushi, Rajashree; Agarwal, Anil; Gautam, Sujeet K; Khuba, Sandeep
Chronic widespread musculoskeletal pain is a cardinal symptom in hypermobility type of Ehler Danlos Syndrome (EDS type III). The management of pain in EDS, however, has not been studied in depth. A 30 year old female, known case of EDS, presented to the pain clinic with complaints of severe upper back pain for 6 months. Physical examination of the back revealed two myofascial trigger points over the left rhomboids and the left erector spinae. Local anaesthetic trigger point injections were given at these points, followed by stretching exercises under analgesic cover for the first week. After 1 week the patient reported 60-80% pain relief. This case highlights that we must keep a high index of suspicion for the more treatable causes of pain like myofascial pain syndrome in patients suffering from EDS, and should address it promptly and appropriately in order to maximise patient comfort. Copyright © 2016 Elsevier Ltd. All rights reserved.
Ahmed, Z M; Riazuddin, S; Khan, S N; Friedman, P L; Riazuddin, S; Friedman, T B
Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date, six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage of USH to the 11 known USH loci and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.
Ferreira, Maria Angelica; Gazzana, Marcelo Basso; Barreto, Sergio Saldanha Menna; Knorst, Marli Maria
Hepatopulmonary syndrome is characterized by a triad consisting of liver disorder, pulmonary vascular dilatation, and hypoxaemia. No case of hepatopulmonary syndrome associated with AIDS has been reported so far. In this study, the authors report the case of a 43-year woman with AIDS and virus C cirrhosis taking prophylactic cotrimoxazole for pneumocystosis and retroviral therapy. Upon admission, the patient presented dyspnoea, cyanosis, digital clubbing, vascular spiders, and normal chest examination. Chest X-ray revealed bilateral interstitial infiltration and evidenced increased alveolar-arterial gradient and liver function impairment. Intrapulmonary shunt was evidenced by contrast-enhanced echocardiography and radionuclide perfusion scanning, thus confirming hepatopulmonary syndrome. (author)
Usinskiene, Jurgita; Mazighi, Mikael; Bisdorff, Annouk; Houdart, Emmanuel
We report the case of a 25-year-old woman treated for a spontaneous carotid-cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization with a transvenous approach was achieved without complications; however, the patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no lesion of the digestive arteries was identified. Possible causes of this bleeding are discussed
Lee, Seok-Soo; Jung, Tae-Eun; Lee, Dong Hyup
Aortic dilatation and dissection are severe complications during pregnancy that can be fatal to both the mother and the fetus. The risks of these complications are especially high in pregnant patients with Marfan syndrome; however, incidents of descending aortic dissection are very rare. This case report involves a successful Bentall procedure for and recovery from a rare aortic dissection in a pregnant Marfan patient who developed acute type II aortic dissection with severe aortic regurgitat...
Cakir Evrim; Ozbek Mustafa; Sahin Mustafa; Cakal Erman; Gungunes Askin; Ginis Zeynep; Demirci Taner; Delibasi Tuncay
Abstract Background Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Heart type fatty acid binding protein (HFABP) has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. Methods This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductiv...
Winqvist, O; Gustafsson, J; Rorsman, F; Karlsson, F A; Kämpe, O
Autoimmune polyendocrine syndrome type I (APS I) and idiopathic Addison's disease are both disorders with adrenal insufficiency but with differences in genetic background, clinical presentation, and extent of extraadrenal manifestations. In this study the major adrenal autoantigen identified with sera from patients with APS I was characterized by analyses using indirect immunofluorescence, Western blots of adrenal subcellular fractions and of recombinant proteins, immunoprecipitations of [35S...
de Courten, Barbora; de Courten, Maximilian; Hanson, Robert L
Gypsies (or Roma) recently experienced a transition from a traditional to a Westernized lifestyle. Although mortality in this population is 4-fold higher compared with non-Gypsies, very limited information is available on their morbidity especially with regard to non-communicable diseases. Our ai...... was to determine the prevalence of type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular diseases in Gypsies and non-Gypsies living in the same region of southern Slovakia....
Fadzilah, Noraziana; Azman, Mawaddah; See, Goh Bee
Lingual hamartoma is a rare finding of congenital midline posterior tongue mass. The lesion may be seen as a single anomaly or maybe associated with syndrome especially the Oral Facial Digital Syndrome (OFDS). Here, we report an otherwise normal and healthy two-month-old boy with a congenital midline base of tongue mass presented with snoring and episodic vomiting since the age of 1 month. Tumour excision from the area of foramen of caecum recovered a pinkish pedunculated tumour. Histopatholo...
Endah Ayu Tri Wulandari
Full Text Available Recurrent Aphthous Stomatitis (RAS is a common inflammatory condition of the oral mucosa. The aetiology of RAS remains unclear, yet there are several predisposing factors which could be involved in the onset of the lesion. The herpetiform type of RAS appeared to be similar to recurrent oral Herpes Simplex infection and also could be part of Behçet Syndrome. This case report discussed a patient suffering from a herpetiform type of RAS with its clinical appearance resembling recurrent oral Herpes Simplex infection and Behçet syndrome. Initial treatment was undertaken based on the empirical treatment, yet the respond was not satisfactory. Then, laboratory tests were undertaken, including complete blood count, the total population of T lymphocyte, B lymphocyte, T helper, T suppressor, NK cells, T helper/T suppressor ratio, C3, C4, IgG, IgA, and IgM. These tests showed that there were immune and hematinic deficiency condition. Nevertheless, the clinical appearance, laboratory findings and consultation did not support the diagnosis of recurrent oral Herpes Simplex infection and Behçet Syndrome, thus, enhancing the definite diagnosis of the herpetiform type of RAS with immune and hematinic deficiency as the underlying condition. Based on the definite diagnosis, treatment plan was then revised to target the underlying condition.
Nomura, Naohiro; Kamiya, Kazusaku; Ikeda, Katsuhisa; Yui, Naofumi; Chiga, Motoko; Sohara, Eisei; Rai, Tatemitu; Sakaki, Sei; Uchida, Shinich
Mutations of BSND, which encodes barttin, cause Bartter syndrome type IV. This disease is characterized by salt and fluid loss, hypokalemia, metabolic alkalosis, and sensorineural hearing impairment. Barttin is the β-subunit of the ClC-K chloride channel, which recruits it to the plasma membranes, and the ClC-K/barttin complex contributes to transepithelial chloride transport in the kidney and inner ear. The retention of mutant forms of barttin in the endoplasmic reticulum (ER) is etiologically linked to Bartter syndrome type IV. Here, we report that treatment with 17-allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, enhanced the plasma membrane expression of mutant barttins (R8L and G47R) in Madin-Darby canine kidney cells. Administration of 17-AAG to Bsnd(R8L/R8L) knock-in mice elevated the plasma membrane expression of R8L in the kidney and inner ear, thereby mitigating hypokalemia, metabolic alkalosis, and hearing loss. These results suggest that drugs that rescue ER-retained mutant barttin may be useful for treating patients with Bartter syndrome type IV. Copyright © 2013 Elsevier Inc. All rights reserved.
Beneyto, M M; Cuevas, J M; Millán, J M; Espinós, C; Mateu, E; González-Cabo, P; Baiget, M; Doménech, M; Bernal, S; Ayuso, C; García-Sandoval, B; Trujillo, M J; Borrego, S; Antiñolo, G; Carballo, M; Nájera, C
The Usher syndrome (USH) is a group of autosomal recessive diseases characterized by congenital sensorineural hearing loss and retinitis pigmentosa. Three clinically distinct forms of Usher syndrome have so far been recognized and can be distinguished from one another by assessing auditory and vestibular function. Usher syndrome type II (USH2) patients have congenital moderate-to-severe nonprogressive hearing loss, retinitis pigmentosa, and normal vestibular function. Genetic linkage studies have revealed genetic heterogeneity among the three types of USH, with the majority of USH2 families showing linkage to the USH2A locus in 1q41. The USH2A gene (MIM 276901) has been identified: three mutations, 2314delG, 2913delG, and 4353-54delC, were initially reported in USH2A patients, the most frequent of which is the 2314delG mutation. It has been reported that this mutation can give rise to typical and atypical USH2 phenotypes. USH2 cases represent 62% of all USH cases in the Spanish population, and 95% of these cases have provided evidence of linkage to the USH2A locus. In the present study, the three reported mutations were analyzed in 59 Spanish families with a diagnosis of USH type II. The 2314delG was the only mutation identified in our population: it was detected in 25% of families and 16% of USH2 chromosomes analyzed. This study attempts to estimate the prevalence of this common mutation in a homogeneous Spanish population.
This study evaluates whether certain patient or parental characteristics are associated with gastroenterology (GI) referral versus primary pediatrics care for pediatric irritable bowel syndrome (IBS). A retrospective clinical trial sample of patients meeting pediatric Rome III IBS criteria was assem...
Young, Deidra; Bebbington, Ami; de Klerk, Nick; Bower, Carol; Nagarajan, Lakshmi; Leonard, Helen
This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over 6 years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use…
Hartel, B.P.; Lofgren, M.; Huygen, P.L.; Guchelaar, I.; Lo, A.N.K.N.; Sadeghi, A.M.; van Wijk, E.; Tranebjaerg, L.; Kremer, H.; Kimberling, W.J.; Cremers, C.W.R.J.; Moller, C.; Pennings, R.J.
OBJECTIVES: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates
Baez, Sandra; Couto, Blas; Herrera, Eduar; Bocanegra, Yamile; Trujillo-Orrego, Natalia; Madrigal-Zapata, Lucia; Cardona, Juan Felipe; Manes, Facundo; Ibanez, Agustin; Villegas, Andres
Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging. PMID:24324434
Sa Rah Lee
Full Text Available BackgroundThe aim of this study is to investigate the cardio-metabolic parameters and surrogate markers of insulin resistance in a discordant group of type 2 diabetes (T2DM subjects who satisfy the Adults Treatment Panel (ATP III criteria, but not the International Diabetes Federation (IDF criteria, for metabolic syndrome (MetS.MethodsWe assessed the prevalence of MetS in T2DM subjects (n=167 who were selected from subjects registered at the diabetes center of Dong-A University Medical Center. We used the ATP III criteria and the IDF criteria for the diagnosis of MetS and sorted the subjects into 2 MetS groups: one group diagnosed per ATP III criteria (MetSa and one diagnosed per IDF criteria (MetSi. We then compared the clinical characteristics, metabolic parameters (homeostasis model assessment of insulin resistance, aspartate aminotransferase, alanine aminotransferase, and uric acid values and co-morbidities (prevalence of microalbuminuria, fatty liver, and cardiovascular disease between the MetSa, MetSi, and discordant MetS groups.ResultsThe prevalence of MetS in the MetSa group (73.6% was higher than in the MetSi group (62.2%. The MetS prevalence in the discordant group was 11.4%. The discordant group showed no significant differences in clinical characteristics (except waist circumference and body mass index, metabolic parameters, or prevalence of co-morbidities, as compared with subjects with MetS by both criteria.ConclusionIn this study, cardio-metabolic features of the subjects diagnosed with MetS using ATP III criteria, but not IDF criteria, are not significantly different from those of subjects diagnosed with MetS using both criteria.
Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K; Duncan, Jacque L
To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. clinicaltrials.gov Identifier: NCT00254605.
Wang, Li; Qin, Litao; Li, Tao; Liu, Hongjian; Ma, Lingcao; Li, Wan; Wu, Dong; Wang, Hongdan; Guo, Qiannan; Guo, Liangjie; Liao, Shixiu
Waardenburg syndrome (WS) is an auditory-pigmentary disorder with varying combinations of sensorineural hearing loss and abnormal pigmentation. The present study aimed to investigate the underlying molecular pathology and provide a method of prenatal diagnosis of WS in Chinese families. A total of 11 patients with WS from five unrelated Chinese families were enrolled. A thorough clinical examination was performed on all participants. Furthermore, patients with WS underwent screening for mutations in the following genes: Paired box 3 (PAX3), melanogenesis associated transcription factor (MITF), SRY-box 10, snail family transcriptional repressor 2 and endothelin receptor type B using polymerase chain reaction sequencing. Array-based comparative genomic hybridization was used for specific patients whose sequence results were normal. Following identification of the genotype of the probands and their parents, prenatal genetic diagnosis was performed for family 01 and 05. According to the diagnostic criteria for WS, five cases were diagnosed as WS1, while the other six cases were WS2. Genetic analysis revealed three mutations, including a nonsense mutation PAX3 c.583C>T in family 01, a splice-site mutation MITF c.909G>A in family 03 and an in-frame deletion MITF c.649_651delGAA in family 05. To the best of the authors' knowledge the mutations (c.583C>T in PAX3 and c.909G>A in MITF) were reported for the first time in Chinese people. Mutations in the gene of interest were not identified in family 02 and 04. The prenatal genetic testing of the two fetuses was carried out and demonstrated that the two babies were normal. The results of the present study expanded the range of known genetic mutations in China. Identification of genetic mutations in these families provided an efficient way to understand the causes of WS and improved genetic counseling. PMID:29115496
Wang, Juan; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming
Purpose To detect paired box gene 3 (PAX3) mutations and associated phenotypes in Chinese patients with Waardenburg syndrome type 1 (WS1). Methods Five unrelated families with suspected WS1 were selected from our Genomic DNA Repository for Hereditary Eye Diseases. The coding and adjacent intronic regions of PAX3 were amplified by polymerase chain reaction and the amplicons were then analyzed by cycle sequencing. Variations detected were further evaluated in available family members as well as one hundred controls with heteroduplex-single strand conformational polymorphism (heteroduplex-SSCP) analysis and/or clone sequencing. Results Three novel and two known mutations in PAX3 were detected in five patients, respectively: c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly), c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT (p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T (p.Arg223X). Two novel mutations proved to be de novo as their parents did not carry the mutations. All five patients with PAX3 mutations had dystopia canthorum and different iris color and fundi between their two eyes. However, none had white forelock, skin hypopigmentation, and deafness. Conclusions Our findings expand the frequency and spectrum of PAX3 mutations and ethnic-related phenotypes in Chinese patients with WS1. De novo mutations in PAX3 have not been reported before. PMID:20664692
Lee, Byung Ha; Gauna, Adrienne E.; Perez, Geidys; Park, Yun-jong; Pauley, Kaleb M.; Kawai, Toshihisa; Cha, Seunghee
Sjögren's syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (α-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFP-tagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced AQP5 trafficking with CCh, compared with HSG-hAQP5 pre-incubated with healthy control (HC) plasma. This inhibition was confirmed by monoclonal α-M3R antibody and pre-absorbed plasma. Interestingly, HSG-hAQP5 pre-incubated with SjS plasma showed no change in cell volume, compared to the cells incubated with HC plasma showing shrinkage by twenty percent after CCh-stimulation. Our findings clearly indicate that binding of anti-M3R autoantibodies to the receptor, which was verified by immunoprecipitation, suppresses AQP5 trafficking to the membrane and contribute to impaired fluid secretion in SjS. Our current study urges further investigations of clinical associations between SjS symptoms, such as degree of secretory dysfunction, cognitive impairment, and/or bladder irritation, and different profiles (titers, isotypes, and/or specificity) of anti-M3R autoantibodies in individuals with SjS. PMID:23382834
Koy, Anne; Assmann, Birgit; Klepper, Joerg; Mayatepek, Ertan
Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by a defect in glucose transport across the blood-brain barrier. The main symptoms are epilepsy, developmental delay, movement disorders, and deceleration of head circumference. A ketogenic diet has been shown to be effective in controlling epilepsy in GLUT1-DS. We report a female child (3 y 4 mo) who presented with delayed psychomotor development and frequent episodes of staggering, impaired vigilance, and vomiting that resolved promptly after food intake. Electroencephalography was normal. The cerebrospinal fluid-blood glucose ratio was 0.42 (normal ≥ 0.45). GLUT1-DS was confirmed by molecular genetic testing, which showed a novel de novo heterozygous mutation in the SLC2A1 gene (c.497_499delTCG, p.VAL166del). Before starting a ketogenic diet, the child's cognitive development was tested using the Snijders-Oomen Non-Verbal Intelligence Test, which revealed a heterogeneous intelligence profile with deficits in her visuomotor skills and spatial awareness. Her motor development was delayed. Three months after introducing a ketogenic diet, she showed marked improvement in speech and motor development, as tested by the Movement Assessment Battery for Children (manual dexterity 16th centile, ball skills 1st centile, static and dynamic balance 5th centile). This case demonstrates that GLUT1-DS should be investigated in individuals with unexplained developmental delay. Epilepsy is not a mandatory symptom. The ketogenic diet is also beneficial for non-epileptic symptoms in GLUT1-DS. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.
El Masri, H; Loong, T-H; Meurette, G; Podevin, J; Zinzindohoue, F; Lehur, P-A
Spontaneous gastrointestinal (GI) perforation is a well-known complication occurring in patients suffering from Type IV vascular Ehlers-Danlos syndrome (EDS IV). The aim of the present study was to review the current literature on spontaneous GI perforation in EDS IV and illustrate the surgical management and outcome when possible. A systematic review of all the published data on EDS IV patients with spontaneous GI perforation between January 2000 and December 2015 was conducted using three major databases PUBMED, EMBASE, and Cochrane Central Register of Controlled Trails. References of the selected articles were screened to avoid missing main articles. Twenty-seven published case reports and four retrospective studies, including 31 and 527 cases, respectively, matched the search criteria. A case from our institution was added. Mean age was 26 years (range 6-64 years). The most frequent site of perforation was the colon, particularly the sigmoid, followed by small bowel, upper rectum, and finally stomach. The majority of cases were initially managed with Hartmann's procedure. In recurrent perforations, total colectomy was performed. The reperforation rate was considerably higher in the "partial colectomy with anastomosis" group than in the Hartmann group. Colonic perforation is the most common spontaneous GI perforation in EDS IV patients. An unexpected fragility of the tissues should raise the possibility of a connective tissue disorder and prompt further investigation with eventual management of these high-risk patients with a multidisciplinary team approach in dedicated centres. In the emergency setting, a Hartmann procedure should be performed.
Ali Al Kaissi
Full Text Available Background: Thoracolumbar kyphosis has been considered as the first presenting deformity and is often a key diagnostic clue noted in children with mucopolysaccharidosis (MPS type IV (Morquio′s syndrome. However, we observed that the progressive irregularities of the epiphyses of the long bones were the most prominent skeletal pathology, causing effectively the development of diverse forms of lower limbs deformities with extreme variation in age of onset. Materials and Methods: Ten patients (seven children and three adults with an average age of 15 years have been enrolled in this study. Age of diagnosis of MPS IVA has a variable age of onset and a MISLEADING rate of severity. Hip dislocations, genu valgum, protrusio acetabuli and osteoarthritis were the most common lower limbs deformities in these patients. Clinical and radiographic phenotypes were the baseline tools of documentation. Urinary screening and genotypic characterizations have been applied accordingly. Results: Combined pelvic and femoral procedures for hip dislocation, epiphysiodeses and supracondylar osteotomy for genu valgum and hip arthroplasty for protrusio acetabuli have been performed. All patients manifested insufficient activity of N-acetylgalactosamine-6-sulphate sulphatase, an enzyme that degrades keratin sulphate and chondroitin-6 sulphate. Conclusion: The extensive clinical heterogeneity contributed significantly in the delay in establishing the diagnosis particularly in adult patients with MPS IV. The epiphyseal irregularities of the long bones and the progressive flattening pathology of MPS IV A were the reason to falsely diagnose some patients as spondyloepiphyseal dysplasia congenital and/or tarda. Proximal femoral osteotomy, realignment osteotomy and total hip arthroplasty have been performed for coxa vara, genu valgum and protrusio acetabuli, respectively, in children and adult group of patients. The importance of early diagnosis on MPS IV A is to receive enzyme
Gahl William A
Full Text Available Abstract Background Hermansky-Pudlak syndrome (HPS is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3 results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE at residues 172–176. Results Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. Conclusion HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking.
Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin
The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397
Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.
Full Text Available Autoimmune polyglandular syndrome type 1 (APS-1, OMIM 240300 is a rare autosomal recessive disorder, characterized by the presence of at least two of three major diseases: hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis. We aim to identify the molecular defects and investigate the clinical and mutational characteristics in an index case and other members of a consanguineous family. We identified a novel homozygous mutation in the splice site acceptor (SSA of intron 5 (c.653-1G>A in two siblings with different clinical outcomes of APS-1. Coding DNA sequencing revealed that this AIRE mutation potentially compromised the recognition of the constitutive SSA of intron 5, splicing upstream onto a nearby cryptic SSA in intron 5. Surprisingly, the use of an alternative SSA entails the uncovering of a cryptic donor splice site in exon 5. This new transcript generates a truncated protein (p.A214fs67X containing the first 213 amino acids and followed by 68 aberrant amino acids. The mutation affects the proper splicing, not only at the acceptor but also at the donor splice site, highlighting the complexity of recognizing suitable splicing sites and the importance of sequencing the intron-exon junctions for a more precise molecular diagnosis and correct genetic counseling. As both siblings were carrying the same mutation but exhibited a different APS-1 onset, and one of the brothers was not clinically diagnosed, our finding highlights the possibility to suspect mutations in the AIRE gene in cases of childhood chronic candidiasis and/or hypoparathyroidism otherwise unexplained, especially when the phenotype is associated with other autoimmune diseases.
Sim, Stephanie Y T; Chin, Sian L; Tan, Jocelyn L K; Brown, Suzanne J; Cussons, Andrea J; Stuckey, Bronwyn G A
To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and without PCOS. Cross-sectional study. Tertiary hospital. Female inpatients age 18-75 years with DM2. A face-to-face questionnaire was administered. Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy. One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m 2 vs. 36.8 kg/m 2 ), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%). A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.
Full Text Available Cockayne syndrome (CS is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind and empathy tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions, which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.
Ben Rebeh, Imen; Benzina, Zeineb; Dhouib, Houria; Hadjamor, Imen; Amyere, Mustapha; Ayadi, Leila; Turki, Khalil; Hammami, Bouthaina; Kmiha, Noureddine; Kammoun, Hassen; Hakim, Bochra; Charfedine, Ilhem; Vikkula, Miikka; Ghorbel, Abdelmonem; Ayadi, Hammadi; Masmoudi, Saber
Chronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to severe hearing impairment with downsloping pure-tone audiogram, and normal vestibular function. Four loci and three genes are known for USH2. In this study, we proposed to localize the gene responsible for USH2 in a consanguineous family of Tunisian origin. Affected members underwent detailed ocular and audiologic characterization. One Tunisian family with USH2 and 45 healthy controls unrelated to the family were recruited. Two affected and six unaffected family members attended our study. DNA samples of eight family members were genotyped with polymorphic markers. Two-point and multipoint LOD scores were calculated using Genehunter software v2.1. Sequencing was used to investigate candidate genes. Haplotype analysis showed no significant linkage to any known USH gene or locus. A genome-wide screen, using microsatellite markers, was performed, allowing the identification of three homozygous regions in chromosomes 2, 4, and 15. We further confirmed and refined these three regions using microsatellite and single-nucleotide polymorphisms. With recessive mode of inheritance, the highest multipoint LOD score of 1.765 was identified for the candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55 Mb), underscoring the limited number of meioses in the consanguineous pedigree. Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data strongly suggest that the novel locus for USH2 is likely to reside on 15q. Our data provide a basis for the localization and the identification of a novel gene implicated in USH2, most likely localized on 15q.
Moceri, Pamela; Kempny, Aleksander; Liodakis, Emmanouil; Alonso Gonzales, Rafael; Germanakis, Ioannis; Diller, Gerhard-Paul; Swan, Lorna; Marino, Philip S; Wort, Stephen J; Babu-Narayan, Sonya V; Ferrari, Emile; Gatzoulis, Michael A; Li, Wei; Dimopoulos, Konstantinos
Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) related to congenital heart disease. Several studies have suggested that the presence and location of the shunt defines the natural history of these patients by influencing right ventricular adaptation to PAH. We aimed to echocardiographically assess differences in cardiac physiology and outcome between various types of ES. In this longitudinal cohort study, 191 patients with ES and non-complex congenital heart disease were recruited, 36 with pre-tricuspid and 155 with post-tricuspid shunts. Patients with pre-tricuspid shunts were older, had higher BNP concentrations and lower exercise tolerance compared to patients with post-tricuspid shunts. Right ventricular (RV) function was impaired in patients with atrial septal defects, with larger right ventricles, impaired systolic function and adaptation. The left ventricular eccentricity index was significantly higher in pre-tricuspid defects. Within post-tricuspid shunts, patients with atrio-ventricular septal defects had better right ventricular function compared to ventricular septal defects, while in those with a patent ductus arteriosus this was worse. There was a trend towards lower mortality in patients with post versus pre-tricuspid shunts, which was significant for patients above the age of 48 years. The presence of a post-tricuspid shunt appears to carry physiological and possibly prognostic benefits in ES compared to patients with pre-tricuspid shunts. This should be borne in mind when management decisions and advanced therapies are considered. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Objective: To investigate working memory, phonological skills, lexical skills, and reading comprehension in adults with Usher syndrome type 2 (USH2.Design: The participants performed tests of phonological processing, lexical access, working memory and reading comprehension. The design of the test situation and tests was specifically considered for use with persons with low vision in combination with hearing impairment. The performance of the group with USH2 on the different cognitive measures was compared to that of a matched control group with normal hearing and vision (NVH.Study Sample: Thirteen participants with USH2 aged 21–60 years and a control group of ten individuals with NVH, matched on age and level of education.Results: The group with USH2 displayed significantly lower performance on tests of phonological processing, and on measures requiring both fast visual judgment and phonological processing. There was a larger variation in performance among the individuals with USH2 than in the matched control group.Conclusions: The performance of the group with USH2 indicated similar problems with phonological processing skills and phonological working memory as in individuals with long-term hearing loss. The group with USH2 also had significantly longer reaction times, indicating that processing of visual stimuli is difficult due to the visual impairment. These findings point toward the difficulties in accessing information that persons with USH2 experience, and could be part of the explanation of why individuals with USH2 report high levels of fatigue and feelings of stress (Wahlqvist et al., 2013.