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Sample records for albright hereditary osteodystrophy

  1. Spinal stenosis with paraparesis in albright hereditary osteodystrophy. Case report and review of the literature.

    NARCIS (Netherlands)

    Lindert, E.J. van; Bartels, R.H.M.A.; Noordam, C.

    2008-01-01

    We describe thoracic spinal stenosis with progressive myelopathy in association with Albright hereditary osteodystrophy (AHO) in a 12-year-old child with delayed diagnosis and review the relevant literature in order to identify the pathophysiological mechanism. The child was successfully treated by

  2. Genetic deficiency of the α subunit of the guanine nucleotide-binding protein G/sub s/ as the molecular basis for Albright hereditary osteodystrophy

    International Nuclear Information System (INIS)

    Levine, M.A.; Ahn, T.G.; Klupt, S.F.; Kaufman, K.D.; Smallwood, P.M.; Bourne, H.R.; Sullivan, K.A.; Van Dop, C.

    1988-01-01

    Patients who have pseudohypoparathyroidism type I associated with Albright hereditary osteodystrophy commonly have a genetic deficiency of the α subunit of the G protein that stimulated adenylyl cyclase αG/sub s/. To discover the molecular mechanism that causes αG/sub s/ deficiency in these patients, the authors examined eight kindreds with one or more members affected with Albright hereditary osteodystrophy or pseudohypoparathyroidism and αG/sub s/ deficiency. In these families, αG/sub s/, deficiency and the Albright hereditary osteodystrophy phenotype were transmitted together in a dominant inheritance pattern. Using a cDNA hybridization probe for αG/sub s/, restriction analysis with several analysis with several endonucleases showed no abnormalities of restriction fragments or gene dosage. RNA blot and dot blot analysis of total RNA from cultured fibroblasts obtained from the patients revealed ∼ 50% reduced mRNA levels for αG/sub s/ in affected members of six of the pedigrees but normal levels in affected members of the two other pedigrees, compared to mRNA levels in fibroblasts from unaffected individuals. By contrast, mRNA levels encoding the α subunit of the G protein that inhibits adenylyl cyclase were not altered. These findings suggest that several molecular mechanisms produce αG/sub s/ deficiency in patients with pseudohypoparathyroidism type Ia and that major gene rearrangements or deletions are not a common cause for αG/sub s/ deficiency in pseudohypoparathyroidism type I

  3. Heterotopic ossifications in a mouse model of albright hereditary osteodystrophy.

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    David L Huso

    Full Text Available Albright hereditary osteodystrophy (AHO is characterized by short stature, brachydactyly, and often heterotopic ossifications that are typically subcutaneous. Subcutaneous ossifications (SCO cause considerable morbidity in AHO with no effective treatment. AHO is caused by heterozygous inactivating mutations in those GNAS exons encoding the α-subunit of the stimulatory G protein (Gα(s. When inherited maternally, these mutations are associated with obesity, cognitive impairment, and resistance to certain hormones that mediate their actions through G protein-coupled receptors, a condition termed pseudohypoparathyroidism type 1a (PHP1a. When inherited paternally, GNAS mutations cause only AHO but not hormonal resistance, termed pseudopseudohypoparathyroidism (PPHP. Mice with targeted disruption of exon 1 of Gnas (Gnas(E1-/+ replicate human PHP1a or PPHP phenotypically and hormonally. However, SCO have not yet been reported in Gnas(E1+/- mice, at least not those that had been analyzed by us up to 3 months of age. Here we now show that Gnas(E1-/+ animals develop SCO over time. The ossified lesions increase in number and size and are uniformly detected in adult mice by one year of age. They are located in both the dermis, often in perifollicular areas, and the subcutis. These lesions are particularly prominent in skin prone to injury or pressure. The SCO comprise mature bone with evidence of mineral deposition and bone marrow elements. Superficial localization was confirmed by radiographic and computerized tomographic imaging. In situ hybridization of SCO lesions were positive for both osteonectin and osteopontin. Notably, the ossifications were much more extensive in males than females. Because Gnas(E1-/+ mice develop SCO features that are similar to those observed in AHO patients, these animals provide a model system suitable for investigating pathogenic mechanisms involved in SCO formation and for developing novel therapeutics for heterotopic bone

  4. Case Report of a Satin Guinea Pig with Fibrous Osteodystrophy That Resembles Human Pseudohypoparathyroidism

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    Miguel Gallego

    2017-01-01

    Full Text Available A case report of a 2-year-old female satin guinea pig with a history of dental overgrowth and lameness and radiological lesions of fibrous osteodystrophy is presented. The most relevant clinical findings were bone demineralization, high level of parathyroid hormone (PTH, normophosphatemia, normal ionized calcium, and low total thyroxine (tT4 with a normal renal function. Long-term treatment was based on teeth coronal reduction and maintaining a balanced diet. PTH measurement was performed with a kit suitable for rats to test 4 different paired samples of guinea pigs and resulted in similar results for each pair of measurements. Two kits routinely employed in dogs and cats failed in measuring PTH in guinea pig serum samples. The ionized calcium, PTH, and tT4 values, not previously reported in similar cases, were obtained. The determination of tT4 could be useful in the diagnosis of fibrous osteodystrophy in guinea pigs. The observed findings show similarity with human pseudohypoparathyroidism type Ia, a disease caused by an inactivating heterozygous mutation of the stimulatory G protein α subunit from the maternal genome that induces multiple hormone resistance and that courses with a syndrome called Albright hereditary osteodystrophy. Naturally occurring pseudohypoparathyroidism in animals has been reported previously only in a ferret.

  5. Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism

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    Sang Jin Kim

    2013-09-01

    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.

  6. Primary palpebral and orbital ossification in pseudo-pseudohypoparathyroidism

    DEFF Research Database (Denmark)

    Klauber, S.; Heegaard, S.; Prause, J.U.

    2002-01-01

    ophthalmology, Albright's heriditary osteodystrophy, ossification, pseudo-pseudohypoparathyroidism, pseodohypoparathyroidism, hypothyroidism, GNAS1 gene, history, eyelid, orbit......ophthalmology, Albright's heriditary osteodystrophy, ossification, pseudo-pseudohypoparathyroidism, pseodohypoparathyroidism, hypothyroidism, GNAS1 gene, history, eyelid, orbit...

  7. Bone scintigraphy in renal osteodystrophy

    International Nuclear Information System (INIS)

    de Graaf, P.; Schicht, I.M.; Pauwels, E.K.J.; te Velde, J.; de Graeff, J.

    1978-01-01

    Bone scintigraphy with Tc-99m HEDP was performed in 30 patients on maintenance hemodialysis, and the results of quantitative analysis were compared wth those of a normal group. To permit this comparison, elevated background activity due to the absence of renal radiotracer excretion was reduced by hemodialysis to levels found in the normals. Histologic proof of renal osteodystrophy had been obtained in all patients. the incidence of radiographic abnormalities was 46%, whereas abnormal scans were found in 25 patients (83%); skeletal lesions were also more pronounced and detected earlier. However, even when the scans appeared normal, the quantitative analysis showed increased skeletal activity in all patients. The total skeletal activity proved to be a good index of the severity of renal osteodystrophy and appeared dependent on both osteomalacia and hyperparathyroidism. These findings show that bone scintigraphy is a sensitive method to detect skeletal involvement in renal osteodystrophy

  8. (Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I

    Science.gov (United States)

    Sano, Shinichiro; Nakamura, Akie; Matsubara, Keiko; Nagasaki, Keisuke; Fukami, Maki; Kagami, Masayo

    2018-01-01

    Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting

  9. Incomplete McCune-Albright Syndrome: A Case Report

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    Nagehan Aslan

    2014-08-01

    Full Text Available Fibrous dysplasia of bone is a genetic, non-inheritable disease that can cause bone pain, bone deformities and fracture. It has a large clinic spectrum from benign monostotic fibrous dysplasia to McCune-Albright syndrome. Rare McCune-Albright syndrome is characterized by precocious puberty, cafe au lait spots and fibrous dysplasia. Herein we presented a case who was preferred to hospital with pathological fractures and diagnosed with Incomplet McCune Albright syndrome because of the lack of endocrine hyperfunction and developed early puberty at clinical course.

  10. MOMO Syndrome with Holoprosencephaly and Cryptorchidism: Expanding the Spectrum of the New Obesity Syndrome

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    Sheetal Sharda

    2011-01-01

    Full Text Available There are multiple genetic disorders with known or unknown etiology grouped under obesity syndromes. Inspite of having multisystem involvement and often having a characteristic presentation, the understanding of the genetic causes in the majority of these syndromes is still lacking. The common obesity syndromes are Bardet-Biedl, Prader-Willi, Alstrom, Albright's hereditary osteodystrophy, Carpenter, Rubinstein-Taybi, Fragile X, and Börjeson-Forssman-Lehman syndrome. The list is ever increasing as new syndromes are being added to it. One of the recent additions is MOMO syndrome, with about five such cases being reported in literature. Expanding the spectrum of clinical features, we report the first case of MOMO syndrome from India with lobar variant of holoprosencephaly and cryptorchidism, which have not been reported previously.

  11. Pseudohypoparathyroidism (a report of 6 patients in a family)

    International Nuclear Information System (INIS)

    Li Rungen; Jiao Xinqiang; Chen Zhilie; Lu Jun; Gao Xin

    2001-01-01

    Objective: To improve the recognition and diagnosis of pseudohypoparathyroidism (PhP). Methods: Six subjects with PhP of 4 generations in one family were investigated and studied. There were 4 males (including 2 deaths) and 2 females. The age of 4 surviving patients was from 8 to 55 years. All cases were proved by clinical biochemistry tests. Plain film of hands and head CT scans were performed in 2 selected patients. Results: The somatotype of Albright hereditary osteodystrophy (AHO) and short fingers and toes were found in all cases. Radiologic features were as follows: (1) short metacarpals and phalanges. (2) skull thickening and symmetrical calcification of basal ganglia. Conclusion: The diagnosis of PHP can be established by close combination of radiologic findings and clinical manifestations

  12. Increased bone radiotracer uptake in renal osteodystrophy

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    de Graaf, P.; Schicht, I.M.; de Graeff, J.; te Velde, J.; Kleiverda, K.; Pauwels, E.K.J.

    1982-04-01

    Bone radiotracer uptake in renal osteodystrophy was investigated in 35 dialysis patients by correlating the results of quantitative bone scintigraphy with those of biochemical and bone morphometric studies. There were highly significant correlations (P < 0.001) between the total skeletal activity and the biochemical (iPTH and alkaline phosphatase), and histologic parameters of hyperparathyroidism. These clinical results strongly suggest that increased bone turnover i.e. hyperparathyroidism, rather than osteomalacia is the major cause of increased skeletal uptake in renal osteodystrophy.

  13. Osteodystrophy in liver cirrhosis

    International Nuclear Information System (INIS)

    Sezai, Shu-ichi; Ishizawa, Suguru; Yoshino, Katsumasa

    1987-01-01

    In order to investigate the osteodystrophy in liver cirrhosis, 21 liver cirrhotic patients having no malignancy and normal renal function were examined by 99m Tc Methylene Diphosphonate (MDP) bone scintigraphy. The cirrhotic subjects consisted of 14 males and 7 females. Their age was 31 - 80, average 55.7 years. The causes of their cirrhotic damage were 1 primary biliary cirrhosis, 9 alcoholic, 2 HB viral and 9 cryptogenic. The contents of their illness showed 9 cases in A, 4 in B and 8 in C of Child's classification. Abnormal hot spot(s) on bone in the cirrhotics could be observed very frequently in 99m Tc MDP bone scintigraphy (47.6 %; 10/21 cases). Those spots were seen more frequently in female and advanced stage of cirrhosis. The number of spot(s) increased also in advanced liver cirrhosis. Serum Ca, P and PTH were in normal range. All of three vitamin D 3 fractions decreased and especially 1,25 (OH) 2 D 3 was depressed more in scinti-positive cases. Metacarpal bone X-p with an alumimum step wedge as a reference was analyzed by a microdensitometry (MD) method (Inoue T et al) and the pattern of osteopathy (i.e. porosis, malacia and poromalacia) was examined according to Sumi Y et al. MD method was not known yet if there was any definite correlation with bone scintigraphy and the osteopathic pattern belonged to border categories. In conclusion, more attension on hepatic osteodystrophy will be significantly necessary due to the fact that it has been found very frequently in liver cirrhosis. 99m Tc MDP bone scintigraphy is a good means for detection of the hepatic osteodystrophy. (author)

  14. Identification of a Novel Mutation in a Pseudohypoparathyroidism Family

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    Zhi-Min Miao

    2011-01-01

    Full Text Available Pseudohypoparathyroidism type Ia (PHP Ia is defined as a series of disorders characterized by multihormone resistance in end-organs and Albright hereditary osteodystrophy (AHO phenotype. PHP Ia is caused by heterozygous inactivating mutations in GNAS, which encodes the stimulatory G-protein alpha subunit (Gsa. A patient with typical clinical manifestations of pseudohypoparathyroidism (PHP (round face, short stature, centripetal obesity, brachydactyly, and multi-hormone resistance: parathyroid hormone (PTH, thyroid-stimulating hormone (TSH, and gonadotropins presented at our center. The sequence of the GNAS gene from the patient and her families revealed a novel missense mutation (Y318H in the proband and her mother. An in vitro Gsa functional study showed that Gsa function was significantly impaired. These results stress the importance of GNAS gene investigation.

  15. Effect of water deionisers on 'fracturing osteodystrophy' and dialysis encephalopathy in Plymouth.

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    Leather, H M; Lewin, I G; Calder, E; Braybrooke, J; Cox, R R

    1981-01-01

    In the Plymouth area, 95 patients with end-stage renal failure have undergone haemodialysis for 6 months or longer. Of the 47 patients beginning dialysis between 1967 and 1973, when water deionisers were not used routinely, a bone disease with multiple fractures, 'fracturing osteodystrophy', occurred in 18 patients and dialysis encephalopathy in 10. Of the 48 patients first dialysing between 1974 and 1979, when water deionisers used commonly, fracturing osteodystrophy occurred in only one and dialysis encephalopathy also in only one. Duration of dialysis without a water deioniser appeared to be the most important factor in the development of these two conditions. The use of water deionisers usually led to healing of fractures in patients with fracturing osteodystrophy and also led to improvement in 4 of the 11 patients with dialysis encephalopathy. Neither condition has occurred in any patient using a water deioniser from the first dialysis. Water deionisers, therefore, appeared to be effective in both the treatment and prevention of fracturing osteodystrophy and dialysis encephalopathy.

  16. Role of bone photonic densitometry in uremic osteodystrophy

    International Nuclear Information System (INIS)

    Specchi Bighi, E.; Baldelli, S.; Argalia, G.

    1987-01-01

    The aim of this investigation is to evaluate the role of bone photonic densitometry in uremic osteodystrophy. Bone mineral contenent (BMC) and bone density (BD) have been measured in 80 hemodialyzed patients by double photonic emission densitometry. Photonic densitometry shows an higher sensibility to quantitative changes in bone mineral contenent than metacarpal index (IM). Photonic densitometry is unable to differentiate osteoporosis from osteomalacia; this differential diagnosis can be obtained by radiological analysis: low BD and low IM means osteoporosis, low BD and resorptive changes in cortical bone means osteomalacia and/or hyperparathyroidism. Photonic densitometry is particulary suitable for uremic osteodystrophy follow-up because of its easy ripetibility and innocuousness and for its close correlation with iPTH variations

  17. Renal osteodystrophy presenting predominantly with osteosclerosis

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    Oriazo Theophilus Akhigbe

    2015-01-01

    Full Text Available Renal osteodystrophy is a skeletal pathology characterized by bone mineralization deficiency, which is a direct result of endocrine and electrolyte derangements that accompany chronic kidney disease. We hereby present a case of a 60-year-old man with chronic renal failure showing classical osseous changes of osteomalacia and osteosclerosis.

  18. Intracranial Hemorrhage Revealing Pseudohypoparathyroidism as a Cause of Fahr Syndrome

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    Abhijit Swami

    2011-01-01

    Full Text Available Pseudohypoparathyroidism is an infrequently encountered disease. It is one of the causes of Fahr syndrome which also is a rare clinical entity caused by multiple diseases. A 4-year-old man hospitalized for sudden onset left hemiparesis and hypertension was diagnosed to have right thalamic and midbrain hemorrhage on plain CT scan of the head which also revealed co-existent extensive intracranial calcifications involving the basal ganglia and cerebellum bilaterally. General physical examination revealed features of Albright hereditary osteodystrophy, goitre, hypertension, left hemiparesis, and signs of cerebellar dysfunction. Laboratory findings suggested hypocalcemia, hyperphosphatemia along with high TSH, low FT4, low FT3, and high anti-TPO antibody. Though bilateral intracranial calcifications are usually encountered as an incidental radiological finding in the CT scan of brain, in this case, the patient admitted for thalamic and midbrain hemorrhage was on investigation for associated intracranial calcification, and goitre was also found to have coexisting pseudohypoparathyroidism and autoimmune hypothyroidism.

  19. Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib).

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    Bastepe, Murat; Altug-Teber, Ozge; Agarwal, Chhavi; Oberfield, Sharon E; Bonin, Michael; Jüppner, Harald

    2011-03-01

    Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Oral manifestations of McCune-Albright syndrome

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    Konidena Aravinda

    2013-01-01

    Full Text Available McCune- Albright Syndrome (MAS is a rare fibrosseous lesion, characterized by a classic triad of polyostotic fibrous dysplasia (PFD, cafι -au-lait macules (CALM and underlying endocrinopathies. We present the oral findings of an interesting case of MAS with relevant review of literature. A 30-year-old male presented to us with swelling of both jaws over a period of two years. Cutaneous examination revealed cafι - au - lait macule over the back, crossing the midline. Skeletal survey showed expansile, osteolytic, mixed radiolucent- radiopaque lesions in skull and jaw bones. Serum alkaline phosphatase was elevated (388 IU/L, with normal calcium, phosphorus, parathyroid hormone and 25 hydroxy vitamin D levels. Diagnosis of McCune- Albright syndrome was made and he was treated with parenteral bisphosphonates (intravenous Zoledronate 4 mg and is under follow up for surgical recontouring of the jaws. Early recognition facilitates better treatment and improves prognosis by reducing the morbidity.

  1. MEDICAL METHODS OF CORRECTION OF RENAL OSTEODYSTROPHY

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    L V Egshatyan

    2014-12-01

    Full Text Available The article presents a literature review summarizing the contemporary data on the effects of drug therapy on various parameters of renal osteodystrophy: phosphate binders, vitamin D preparations, bisphosphonates, denosumab, and calcimimetics. We discuss the results of pilot study of the efficacy of teriparatide and denosumab on parameters of bone metabolism in patients with chronic kidney disease.

  2. OPG/RANKL/RANK cytokine system in renal osteodystrophy

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    Ivica Avberšek-Lužnik

    2007-11-01

    Full Text Available Background: Renal osteodystrophy is one of the most common complications affecting patients with endstage renal disease treated with hemodialysis (HD. The action of calciotropic hormones in renal osteodystrophy is regulated by the OPG/RANKL/RANK system. Its function is modulated by interleukines, calcitriol and parathyroid hormone (PTH.The aim of our study was to confirm that this system is involved in the pathogenesis of renal osteodystrophy and supports the mechanism of PTH action on bone.Methods: 106 HD patients (mean age 60 years and 50 healthy volunteers (mean age 64 years were enrolled in the study. In serum samples of patients and controls we determined concentrations of OPG, RANKL, tartarat resistant acid phosphatase 5b (TRAP 5b, serum Cterminal telopeptide cross-links of type I collagen (CTx, bone specific alkaline phosphatase (BALP, osteocalcin (OC and parathyroid hormone (PTH. We compared serum measurements of HD patients and controls and assessed the correlation of OPG and RANKL with bone markers. The most frequent OPG promotor gene polymorphisms were also determined. SPSS 12.1 for Windows was used for statistical analysis.Results: Median OPG concentrations were approximately three times higher in HD patients (0.804 µg/l than in healthy volunteers (0.272 µg/l. Mean serum RANKL concentrations were 1.66- fold higher in HD patients (1.36 pmol/l than in controls (0.82 pmol/l. Serum RANKL levels significantly differed between patients with and without calcitriol therapy (p = 0.001. After dividing HD patients into tertiles according to PTH, we observed significantly higher OPG values in the lower and RANKL in the upper tertile (p < 0.001. OPG did not correlate with bone resorption markers. Only weak correlation of bone formation markers with osteocalcin was noted. In contrast to OPG, RANKL correlated well with PTH, OC and CTX. OPG promoter gene polymorphisms (149 T → C, 163 A → G, 950 T → C do not influence OPG expression and

  3. Mazabraud syndrome associated with McCune-Albright syndrome: a case report and review of the literature.

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    Biazzo, Alessio; Di Bernardo, Andrea; Parafioriti, Antonina; Confalonieri, Norberto

    2017-08-23

    Mazabraud syndrome is a very rare benign disorder characterized by the association of monostotic or polyostotic fibrous dysplasia and one or multiple intramuscular myxomas. McCune -Albright syndrome is a rare benign disorder characterized by the association of polyostotic fibrous dysplasia, cafè-au-lait skin pigmentations and endocrine dysfunction, such as precocious puberty, diabetes mellitus, goiter and breast fibroadenomatosis. The association of Mazabraud syndrome and McCune-Albright in the same patient is an anecdotal event. We report the case of a 28-year-old girl with Mazabraud syndrome associated with McCune-Albright syndrome. Our literature review shows that in these patients there is a higher risk of malignant transformation of fibrous dysplasia into osteosarcoma, confirming previous reports. Conversely, no malignant transformation has been reported for myxomas in isolated Mazabraud syndrome or in the association with McCune-Albright syndrome. We conclude that these patients should be scheduled to a close and long-term follow-up.

  4. The prevalence of radiological markers of renal osteodystrophy in ...

    African Journals Online (AJOL)

    Objectives: To study the prevalence of renal osteodystrophy in Chronic renal failure patients in Enugu, using radiological methods. Subjects and Methods: Ninety adult patients (56 male and 34 female) were recruited from the renal clinics of the University of Nigeria Teaching Hospital, Enugu over a period of twelve ...

  5. McCune-Albright Syndrome: A Case Report and Literature Review

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    Moein Mobini

    2014-04-01

    Full Text Available McCune-Albright syndrome (MAS is a rare, heterogenous, clinical condition caused by a rare genetic mutation. The disorder is more common in females and is characterized by a triad of cutaneous, bone and endocrine abnormalities.  We describe a girl patient with MAS having precocious puberty and multiple cafe-au-lait macules and deforming polyostotic fibrous dysplasia of bone. Clinical presentation and X-ray finding were strongly diagnostic for MAS, Patients with McCune-Albright syndrome reach the adult age with a significant burden of the disease that continuously reduces their quality of life. Skeletal deformities, fractures, hyperthyroidism, and hyperestrogenism are just few of the many challenges in the management of these patients. These disorders with close observation and early detection can be controlled.

  6. Renal osteodystrophy in non-dialysed patients with chronic renal failure

    International Nuclear Information System (INIS)

    Andresen, J.; Nielsen, H.E.

    1980-01-01

    Radiologic bone lesions in 92 non-dialysed patients with chronic renal failure are described. The bone disease increased with the severity of renal failure. In a prospective series of 20 patients progression of osteodystrophy and decrease in metacarpal bone mass were demonstrated. (Auth.)

  7. Special radiology of the hand in renal osteodystrophy

    International Nuclear Information System (INIS)

    Bosnjakovic-Buescher, S.; Heuck, F.

    1986-01-01

    The multiple morphological manifestations in the bones of the hand in renal osteodystrophy are demonstrated. The soft tissue immersion low-energy X-ray technique allows early detection of macrostructural changes of spongy and compact bone, irregularities of the cortex, defects and pseudocysts, osteosclerosis as well as calcifications in the soft tissue and arterial sclerosis of patients with chronic renal failure. Possible misinterpretations will be discussed. (orig.) [de

  8. Quantitative bone scintigraphy in evaluating treatment of renal osteodystrophy

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    de Graaf, P.; Schicht, I.M.; te Velde, J.; Pauwels, E.K.J.; Kleiverda, K.; de Graeff, J. (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis)

    1983-01-01

    The effect of various forms of treatment of renal osteodystrophy was evaluated in 25 dialysis patients by quantitative bone scintigraphy, using 99m-Tc-HEDP. The results were compared with those of biochemical and bone morphometric studies. The total skeletal activity (TSA) decreased in 5 patients after transplantation, in 11 after parathyroidectomy and in 6 out of 9 treated conservatively, but did not normalize in any of the patients. Bone morphometric evaluation of treatment, which could be performed in 19 of the 20 patients who did not receive a transplant, demonstrated a reduction in the degree of hyperparathyroidism in 17 patients (89 percent). Osteoid excess was reduced in 13 patients (68 percent) but an evident reduction of osteomalacic osteoid, i.e. improvement of osteomalacia, occurred in only 4 patients (21 percent). Changes in the TSA correlated significantly with the changes in the biochemical and histological parameters of hyperparathyroidism, but not with the changes in osteoid excess. These results indicate that, during treatment of renal osteodystrophy, changes in (quantitative) bone scintigraphy primarily indicate changes in the degree of hyperparathyroidism.

  9. Imaging of renal osteodystrophy

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    Jevtic, V. E-mail: vladimir.jevtic@mf.uni-lj.si

    2003-05-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  10. Imaging of renal osteodystrophy

    International Nuclear Information System (INIS)

    Jevtic, V.

    2003-01-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination

  11. A rare cause of acromegaly: McCune-Albright syndrome

    Directory of Open Access Journals (Sweden)

    Erdal Bodakçi

    2015-06-01

    Full Text Available McCune-Albright syndrome is characterized by polyostatic fibrous dysplasia, brown spots on the skin (café au lait pigmentation and autonomous endocrine hyperfunction. Early puberty and other endocrinological manifestations, such as acromegaly, gigantism and hypercortisolism are widely observed in the syndrome. Acromegaly is seen in 20% of patients. We report a case of acromegaly accompanied with this syndrome.

  12. Comparative assessment of the clinical and X-ray picture of urenic osteodystrophy before and after parathyroidectomy

    International Nuclear Information System (INIS)

    Ratobyl'skij, G.V.; Suslov, V.P.; Ivanov, I.A.; Loseva, T.V.

    1992-01-01

    The results of clinical, X-ray, and biochemical studies carried out in 51 patients with uremic osterodystrophy, treated with hemodialysis, before and after parathyroidectomy are presented. The patients were divided into 4 groups with various patterns of X-ray symptoms. Analysis of the clinical and X-ray data before and after parathyroidectomy has brought to a conclusion that such an intervention was effective only in cases with manifest clinical and X-ray symptoms of fibrous osteodystrophy. Surgical treatment is containdicated to patients in whom X-ray signs of osteomalacia predominate over fibrous osteodystrophy; it may result in a rap[id progress of osteomalacia

  13. Renal osteodystrophy with facial hyperostosis and 'rubber jaw' in an adult dog.

    Science.gov (United States)

    Kyle, M G; Davis, G B; Thompson, K G

    1985-07-01

    A nine-year-old male Sheltie dog was presented with bilaterally symmetrical maxilliary swelling, loose teeth and flexible mandibles. The condition was progressive over a period of two months. Biochemical and histopathological examinations supported a diagnosis of renal osteodystrophy with facial hyperostosis and 'rubber jaw'.

  14. Hansen′s disease with McCune-Albright syndrome

    Directory of Open Access Journals (Sweden)

    KVS Hari Kumar

    2012-01-01

    Full Text Available McCune-Albright syndrome (MAS comprises a triad of fibrous dysplasia of bone, cafι-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen′s disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen′s disease along with underlying MAS and report the same in this report.

  15. Pseudohypoparathyroidism vs. tricho-rhino-phalangeal syndrome: patient reclassification.

    Science.gov (United States)

    Pereda, Arrate; Azriel, Sharona; Bonet, Mariona; Garin, Intza; Gener, Blanca; Lecumberri, Beatriz; de Nanclares, Guiomar Pérez

    2014-11-01

    Given that tricho-rhino-phalangeal syndrome (TRPS) and pseudohypoparathyroidism/pseudopseudohypoparathyroidism (PHP/PPHP) are very rare monogenic disorders that share some features (distinctive facies, short stature, brachydactyly and, in some patients, intellectual disability) that lead to their misdiagnosis in some cases, our objective was to identify clinical, biochemical or radiological signs that could help to distinguish these two syndromes. We report on two cases, which were referred to the Endocrinology and Pediatric Endocrinology Services for obesity. Clinical evaluation initially suggested the diagnosis of PHP-Ia [phenotype suggestive of Albright hereditary osteodystrophy (AHO) with parathyroid hormone (PTH) resistance] and PPHP (phenotype resembling AHO, without PTH resistance), but (epi)genetic analysis of the GNAS locus ruled out the suspected diagnosis. Further clinical re-evaluation prompted us to suspect TRPS, and this was confirmed genetically. TRPS was mistakenly identified as PHP/PPHP because of the coexistence of obesity and brachydactyly, with PTH resistance in one of the cases. Specific traits such as sparse scalp hair and a pear-shaped nose, present in both cases, can be considered pathognomonic signs of TRPS, which could help us to reach a correct diagnosis.

  16. McCune-Albright syndrome: evaluation of craniofacial involvement through magnetic resonance images

    International Nuclear Information System (INIS)

    Poma, A.; Baganz, M.; Gutierrez, G.

    1999-01-01

    We report the case of a male teenager with the classical clinical picture of McCune-Albright syndrome, with precocious puberty, cafe-au-lait spots, polyostotic fibrous dysplasia and gigantism. Magnetic resonance images are described and a review of the perspective literature is also presented. (authors)

  17. Bone Canopies in Pediatric Renal Osteodystrophy

    DEFF Research Database (Denmark)

    Pereira, Renata C; Levin Andersen, Thomas; Friedman, Peter A

    2016-01-01

    Pediatric renal osteodystrophy (ROD) is characterized by changes in bone turnover, mineralization, and volume that are brought about by alterations in bone resorption and formation. The resorptive and formative surfaces on the cancellous bone are separated from the marrow cavity by canopies...... and their association with biochemical and bone histomorphometric parameters in 106 pediatric chronic kidney disease (CKD) patients (stage 2-5) across the spectrum of ROD. Canopies in CKD patients often appeared as thickened multilayered canopies, similar to previous reports in patients with primary hyperparathyroidism....... This finding contrasts with the thin appearance reported in healthy individuals with normal kidney function. Furthermore, canopies in pediatric CKD patients showed immunoreactivity to the PTH receptor (PTHR1) as well as to the receptor activator of nuclear factor kappa-B ligand (RANKL). The number of surfaces...

  18. Nutritional fibrous osteodystrophy in goats

    Directory of Open Access Journals (Sweden)

    Paulo M Bandarra

    2011-10-01

    Full Text Available Seven out of 25 goats from a southern Brazilian flock developed nutritional fibrous osteodystrophy. Affected animals were younger than 1 year of age and were confined in stalls and fed a concentrate ration containing 1:6 calcium:phosphorus ratio. The remaining flock (35 goats was managed at pasture and showed no disease. Clinical signs were characterized by mandibular and maxillary enlargements, varying degrees of mouth opening and protruding tongue, dyspnea, apart of abnormalities of prehension and mastication. Affected animals had increased seric levels of phosphorus and parathormone, as well as higher alkaline phosphatase activity. Postmortem examination on three succumbed goats revealed bilateral enlargement of the maxilla and mandibula, and loose teeth, apart of multiple incomplete rib fractures in one of them. Severe diffuse proliferation of loose connective tissue surrounded the osteoid trabeculae, many of which were partially or completely non-mineralized. Mineralized osteoid trabeculae showed osteoclasts in the Howship's lacunae.

  19. McCune-Albright syndrome: radiological and MR findings.

    Science.gov (United States)

    Yongjing, G; Huawei, L; Zilai, P; Bei, D; Hao, J; Kemin, C

    2001-01-01

    McCune-Albright syndrome (MAS) is a non-inherited disorder due to the GNAS1 gene mutation. The syndrome is characterized with the triad of polyostotic fibrous dysplasia, pigmented skin lesions, endocrinopathy, and precocious puberty. We report the case of a 14-year-old boy, presenting with sclerotic type of polyostotic fibrous dysplasia. Radiological methods including plain X-ray film, MR and whole body bone scintigraphy suggested the diagnosis of MAS. MRI provided more directly perceived images and it was more sensitive in demonstrating the lesion: its shape, contents, especially the size of the affected region. Histopathological study and the identification of mutant gene finally confirmed the diagnostic result.

  20. McCune Albright syndrome in association with excessive GH secretion: case report.

    Science.gov (United States)

    Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

    2015-06-01

    McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

  1. Osteodystrophy in liver cirrhosis. Its demonstration by 99m Tc methylene diphosphonate bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Sezai, Shu-ichi; Ishizawa, Suguru; Yoshino, Katsumasa

    1987-10-01

    In order to investigate the osteodystrophy in liver cirrhosis, 21 liver cirrhotic patients having no malignancy and normal renal function were examined by 99m Tc Methylene Diphosphonate (MDP) bone scintigraphy. The cirrhotic subjects consisted of 14 males and 7 females. Their age was 31 - 80, average 55.7 years. The causes of their cirrhotic damage were 1 primary biliary cirrhosis, 9 alcoholic, 2 HB viral and 9 cryptogenic. The contents of their illness showed 9 cases in A, 4 in B and 8 in C of Child's classification. Abnormal hot spot(s) on bone in the cirrhotics could be observed very frequently in 99m Tc MDP bone scintigraphy (47.6 %; 10/21 cases). Those spots were seen more frequently in female and advanced stage of cirrhosis. The number of spot(s) increased also in advanced liver cirrhosis. Serum Ca, P and PTH were in normal range. All of three vitamin D/sub 3/ fractions decreased and especially 1,25 (OH)/sub 2/D/sub 3/ was depressed more in scinti-positive cases. Metacarpal bone X-p with an alumimum step wedge as a reference was analyzed by a microdensitometry (MD) method (Inoue T et al) and the pattern of osteopathy (i.e. porosis, malacia and poromalacia) was examined according to Sumi Y et al. MD method was not known yet if there was any definite correlation with bone scintigraphy and the osteopathic pattern belonged to border categories. In conclusion, more attension on hepatic osteodystrophy will be significantly necessary due to the fact that it has been found very frequently in liver cirrhosis. 99m Tc MDP bone scintigraphy is a good means for detection of the hepatic osteodystrophy.

  2. Metacarpal sign

    Directory of Open Access Journals (Sweden)

    Barbara Nieradko-Iwanicka

    2018-02-01

    Full Text Available Background Archibald's sign, or metacarpal sign is defined as shortening of the IV and V metacarpal bones, is a rare phenomenon found in the Turner syndrome, homocystinuria and in Albright's osteodystrophy. Objectives The aim of the article was to show a rare case of metacarpal sign with atypical shortening of the III and IV metacarpal bones not connected with gonadal dysgenesia, genetic disorders nor osteodystrophy. Material and methods Case report of a 60-year-old female patient. Results Artchibald's metacarpal sign in the described case was accompanied by erosive arthritis in the left lower extremity. No features of genetic disorders nor gonadal disgenesia were found in the patient. Undifferentiated seronegative asymmetric erosive arthritis developed in the patient. The level of parathormon was within the normal range. No signs of tumor were seen in bone scintigraphy. Conclusions Archibald's metacarpal sign may be present in patients without genetic disorders.

  3. Radioiodine treatment in McCune-Albright syndrome with hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Dhritiman Chakraborty

    2012-01-01

    Full Text Available McCune-Albright syndrome (MAS is a sporadic disease characterized by polyostotic fibrous dysplasia, "café-au-lait" spots and hyperfunctional endocrinopathies. Pathophysiological basis is activating mutation of the gene that encodes the alpha subunit of Gs membrane protein that stimulates the intracellular production of cAMP, conferring autonomous secretion of the gland in particular. One of the uncommon endocrine manifestations is hyperthyroidism. We present a patient who had café-au-lait spots, polyostotic fibrous dysplasia and hyperthyroidism. She was treated with radioactive iodine for the symptoms of hyperthyroidism and subsequently relieved from hyperthyroid features.

  4. Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

    Science.gov (United States)

    Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

    2018-05-01

    GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Fibrous osteodystrophy in two Northern Royal albatross chicks (Diomedea sanfordi).

    Science.gov (United States)

    Morgan, K J; Alley, M R; Gartrell, B D; Thompson, K G; Perriman, L

    2011-09-01

    In February 2004, two Northern Royal albatross chicks aged 20 and 25 days old were presented for necropsy. Both chicks had been hand-fed in situ at a breeding colony, from 2-3 days post-hatch. The hand-rearing diet consisted of boneless hoki fillets (Macraronus novaezelandiae), electrolytes, and sooty shearwater (Puffinus griseus) proventricular oil obtained as a by-product of cultural harvest. Routine necropsies on the affected chicks revealed many bones were soft and easily bent. Radiography and histopathology revealed decreased bone density, pathological fractures, and extensive remodelling suggestive of fibrous osteodystrophy. Nutritional secondary hyperparathyroidism, resulting from an imbalance in the dietary Ca:P ratio. The imbalance in the dietary Ca:P ratio was a result of feeding deboned and eviscerated fish. This investigation also highlighted potential health risks associated with the practice of feeding stored rancid proventricular oil, including the destruction of fat-soluble vitamins. It is therefore possible that oxidative degradation of vitamin D may have contributed to the development of nutritional secondary hyperparathyroidism. Subsequently, dietary recommendations for supplementary feeding of orphaned Northern Royal albatross chicks include the feeding of whole human-grade fish with an appropriate Ca:P ratio, and the exclusion of proventricular oil. These cases highlight the need for scientific input into wildlife conservation projects, as lack of appropriate nutritional advice resulted in the feeding of a nutritionally inadequate diet. Following the recommended changes in diet, no further cases of osteodystrophy have been diagnosed in hand-raised chicks in the albatross colony.

  6. Síndrome de McCune Albright

    Directory of Open Access Journals (Sweden)

    Milvia Castillo Guerrero

    2014-08-01

    Full Text Available El síndrome de McCune-Albright es una enfermedad esporádica de causa genética, no hereditaria, clínicamente caracterizada por displasia fibrosa poliostótica, manchas de color café con leche y desórdenes endocrinos, tales como hipertiroidismo y pubertad precoz. Se reporta el caso de un paciente masculino de 10 años, que presentó múltiples fracturas óseas desde los seis meses de edad, hipertiroidismo y desnutrición severa, que causaron retardo en su crecimiento y desarrollo. El proceso de diagnóstico fue demorado por su inusual forma de presentación, pero su evolución después de iniciar el tratamiento fue favorable. Se presenta el caso por la baja frecuencia de este trastorno, asociado a complicaciones endocrino-metabólicas graves que causan la muerte, si no se diagnostica y se trata precozmente

  7. McCune Albright syndrome in association with excessive GH secretion: case report

    OpenAIRE

    Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

    2015-01-01

    McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious p...

  8. Hereditary Diffuse Gastric Cancer

    Science.gov (United States)

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

  9. McCune Albright syndrome - association of fibrous dysplasia, café-au-lait skin spots and hyperthyroidism - case report.

    Science.gov (United States)

    Raus, Iulian; Coroiu, Roxana Elena

    2016-01-01

    McCune-Albright syndrome is a rare sporadic disease characterized by bone fibrous dysplasia, café-au-lait skin spots and a variable association of hyperfunctional endocrine disorders. Fibrous dysplasia (FD), which can involve the craniofacial, axial, and appendicular skeleton, may range from an isolated, asymptomatic monostotic lesion to a severe disabling polyostotic disease involving the entire skeleton. A twenty-five-year old male patient presented to our clinic with recently developed heart palpitations. He had also been feeling pain in the right femur since he was younger, without any trauma history, leading to difficulties of ambulation and limping occasionally. His physical examination revealed café-au-lait spots with irregular borders and right testicular agenesis. Laboratory findings identified hyperthyroidism with hyperparathyroidism. Radiographs of the pelvis revealed multiple lytic lesions of the right femur and magnetic resonance imaging (MRI) characterized these lesions as specific to fibrous dysplasia of the bone, without any insufficiency fracture at this level. The association of café-au-lait skin spots with bone fibrous dysplasia, and hyperthyroidism in this patient suggested the diagnosis of McCune - Albright syndrome.

  10. Dental Perspectives in Fibrous Dysplasia and McCune-Albright Syndrome

    Science.gov (United States)

    Akintoye, Sunday O.; Boyce, Alison M.; Collins, Michael T.

    2013-01-01

    McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (PFD), endocrine disorders and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain and compromised oral health. Maxillo-mandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There is limited data on the outcomes of dental treatments in maxillo-mandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillo-mandibular FD within the context of MAS. PMID:23953425

  11. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

    Directory of Open Access Journals (Sweden)

    Duarte M.E.L.

    2002-01-01

    Full Text Available Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha, IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha and transforming growth factor-ß (TGF-ß using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

  12. Polyostotic fibrous dysplasia with gigantism and huge pelvic tumor: a rare case of McCune-Albright syndrome.

    Science.gov (United States)

    Sakayama, Kenshi; Sugawara, Yoshifumi; Kidani, Teruki; Fujibuchi, Taketsugu; Kito, Katsumi; Tanji, Nozomu; Nakamura, Atsushi

    2011-06-01

    We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

  13. Genetics Home Reference: hereditary pancreatitis

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Hereditary pancreatitis Hereditary pancreatitis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Hereditary pancreatitis is a genetic condition characterized by recurrent episodes ...

  14. Resolution of lameness associated with Scottish fold osteodystrophy following bilateral ostectomies and pantarsal arthrodeses: a case report

    International Nuclear Information System (INIS)

    Mathews, K.G.; Koblik, P.D.; Knoeckel, M.J.; Pool, R.R.; Fyfe, J.C.

    1995-01-01

    Bilateral hind-limb lameness, associated with tarsal exostoses in a Scottish fold diagnosed as having Scottish fold osteodystrophy, resolved following staged bilateral ostectomies and pantarsal arthrodeses. Degenerative changes in the phalangeal joints of the hind limbs have progressed radiographically, but lameness has not recurred 48 weeks following the second arthrodesis. Additional skeletal abnormalities were detected radiographically in both carpi and in several caudal vertebrae. A partial, left-sided conduction deafness was diagnosed by evaluating brain stem auditory-evoked responses

  15. A case of atypical McCune-Albright syndrome requiring optic nerve decompression.

    Science.gov (United States)

    Yavuzer, R; Khilnani, R; Jackson, I T; Audet, B

    1999-10-01

    McCune-Albright syndrome (MAS) is a disease of noninheritable, genetic origin defined by the triad of café-au-lait pigmentation of the skin, precocious puberty, and polyostotic fibrous dysplasia. This syndrome, which affects young girls primarily, has also been reported with other endocrinopathies, and rarely with acromegaly and hyperprolactinemia. The fibrous dysplasia in MAS is of the polyostotic type and, apart from the characteristic sites such as the proximal aspects of the femur and the pelvis, the craniofacial region is frequently involved. A male patient with MAS presented with juvenile gigantism, precocious puberty, pituitary adenoma-secreting growth hormone and prolactin, hypothalamic pituitary gonadal and thyroid dysfunction, and polyostotic fibrous dysplasia causing optic nerve compression. Visual deterioration and its surgical management are presented.

  16. Genetics Home Reference: hereditary fructose intolerance

    Science.gov (United States)

    ... Twitter Home Health Conditions Hereditary fructose intolerance Hereditary fructose intolerance Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Hereditary fructose intolerance is a condition that affects a person's ...

  17. Gigantism treated by pure endoscopic endonasal approach in a case of McCune-Albright syndrome with sphenoid fibrous dysplasia: a case report.

    Science.gov (United States)

    Sharifi, Guive; Jalessi, Maryam; Sarvghadi, Farzaneh; Farhadi, Mohammad

    2013-12-01

    McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor. Georg Thieme Verlag KG Stuttgart · New York.

  18. Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus.

    Directory of Open Access Journals (Sweden)

    Gustavo Perez-Nanclares

    Full Text Available Pseudohypoparathyroidism type 1b (PHP-Ib is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype.The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib.We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib.We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising ∼ 320 kb, occurred 'de novo' in the patient, whereas the other one, of ∼ 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed.In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both are associated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.

  19. Current Nomenclature of Pseudohypoparathyroidism: Inactivating Parathyroid Hormone/Parathyroid Hormone-Related Protein Signaling Disorder.

    Science.gov (United States)

    Turan, Serap

    2017-12-30

    Disorders related to parathyroid hormone (PTH) resistance and PTH signaling pathway impairment are historically classified under the term of pseudohypoparathyroidism (PHP). The disease was first described and named by Fuller Albright and colleagues in 1942. Albright hereditary osteodystrophy (AHO) is described as an associated clinical entity with PHP, characterized by brachydactyly, subcutaneous ossifications, round face, short stature and a stocky build. The classification of PHP is further divided into PHP-Ia, pseudo-PHP (pPHP), PHP-Ib, PHP-Ic and PHP-II according to the presence or absence of AHO, together with an in vivo response to exogenous PTH and the measurement of Gsα protein activity in peripheral erythrocyte membranes in vitro. However, PHP classification fails to differentiate all patients with different clinical and molecular findings for PHP subtypes and classification become more complicated with more recent molecular characterization and new forms having been identified. So far, new classifications have been established by the EuroPHP network to cover all disorders of the PTH receptor and its signaling pathway. Inactivating PTH/PTH-related protein signaling disorder (iPPSD) is the new name proposed for a group of these disorders and which can be further divided into subtypes - iPPSD1 to iPPSD6. These are termed, starting from PTH receptor inactivation mutation (Eiken and Blomstrand dysplasia) as iPPSD1, inactivating Gsα mutations (PHP-Ia, PHP-Ic and pPHP) as iPPSD2, loss of methylation of GNAS DMRs (PHP-Ib) as iPPSD3, PRKAR1A mutations (acrodysostosis type 1) as iPPSD4, PDE4D mutations (acrodysostosis type 2) as iPPSD5 and PDE3A mutations (autosomal dominant hypertension with brachydactyly) as iPPSD6. iPPSDx is reserved for unknown molecular defects and iPPSDn+1 for new molecular defects which are yet to be described. With these new classifications, the aim is to clarify the borders of each different subtype of disease and make the classification

  20. McCune-Albright syndrome

    Directory of Open Access Journals (Sweden)

    Collins Michael T

    2008-05-01

    Full Text Available Abstract McCune-Albright syndrome (MAS is classically defined by the clinical triad of fibrous dysplasia of bone (FD, café-au-lait skin spots, and precocious puberty (PP. It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys, other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention

  1. Hereditary pancreatitis for the endoscopist

    OpenAIRE

    Patel, Milan R.; Eppolito, Amanda L.; Willingham, Field F.

    2013-01-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis trans...

  2. McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

    Science.gov (United States)

    Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

    2006-05-01

    McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

  3. Hereditary angioedema.

    Science.gov (United States)

    Bracho, Francisco A

    2005-11-01

    Hereditary angioedema is an autosomal-dominant deficiency of C1 inhibitor--a serpin inhibitor of kallikrein, C1r, C1s, factor XII, and plasmin. Quantitative or qualitative deficiency of C1 inhibitor leads to the generation of vasoactive mediators, most likely bradykinin. The clinical syndrome is repeated bouts of nonpruritic, nonpitting edema of the face, larynx, extermities, and intestinal viscera. Recently, investigators, physicians, and industry have demonstrated a renewed interest in the biology and treatment of hereditary angioedema. Investigators have generated a C1INH-/- mouse model that has demonstrated the importance of the contact activation system for hereditary angioedema-related vascular permeability. An interactive database of mutations is available electronically. Investigators have continued exploration into mRNA/protein levels. The proceedings of a recent workshop have been impressive in the scope and depth. Clinicians have produced consensus documents and expert reviews. The pharmaceutical industry has initiated clinical trails with novel agents. Hereditary angioedema is often misdiagnosed and poorly treated. Diagnosis requires careful medical and family history and the measurement of functional C1 inhibitor and C4 levels. Attenuated androgens, anti-fibrinolytics, and C1 inhibitor concentrates are used for long-term and preprocedure prophylaxis, but have significant drawbacks. C1 inhibitor concentrates and fresh frozen plasma are available for acute intervention. The mainstays of supportive care are airway monitoring, pain relief, hydration, and control of nausea. New agents such as recombinant C1 inhibitor, kallikrein inhibitors, and bradykinin inhibitors may offer safer and more tolerable treatments.

  4. Hereditary forms of breast cancer

    International Nuclear Information System (INIS)

    Bella, V.

    2009-01-01

    Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)

  5. Improving patient outcomes in fibrous dysplasia/McCune-Albright syndrome: an international multidisciplinary workshop to inform an international partnership.

    Science.gov (United States)

    Boyce, A M; Turner, A; Watts, L; Forestier-Zhang, L; Underhill, A; Pinedo-Villanueva, R; Monsell, F; Tessaris, D; Burren, C; Masi, L; Hamdy, N; Brandi, M L; Chapurlat, R; Collins, M T; Javaid, Muhammad Kassim

    2017-12-01

    To develop consensus on improving the management of patients, we convened an international workshop involving patients, clinicians, and researchers. Key findings included the diagnostic delay and variability in subsequent management with agreement to develop an international natural history study. We now invite other stakeholders to join the partnership. The aim of this study was develop a consensus on how to improve the management of patients with fibrous dysplasia and prioritize areas for research METHODS: An international workshop was held over 3 days involving patients, clinicians, and researchers. Each day had a combination of formal presentations and facilitated discussions that focused on clinical pathways and research. The patient workshop day highlighted the variability of patients' experience in getting a diagnosis, the knowledge of general clinical staff, and understanding long-term outcomes. The research workshop prioritized collaborations that improved understanding of the contemporary natural history of fibrous dysplasia/McCune-Albright syndrome (FD/MAS). The clinical workshop outlined the key issues around diagnostics, assessment of severity, treatment and monitoring of patients. In spite of advances in understanding the genetic and molecular underpinnings of fibrous dysplasia/McCune-Albright syndrome, clinical management remains a challenge. From the workshop, a consensus was reached to create an international, multi-stakeholder partnership to advance research and clinical care in FD/MAS. We invite other stakeholders to join the partnership.

  6. Familial association of pseudohypoparathyroidism and psoriasis: case report

    Directory of Open Access Journals (Sweden)

    Renan Magalhães Montenegro Junior

    2002-01-01

    Full Text Available CONTEXT: The association between psoriasis and hypoparathyroidism has been reported by several authors, and it has been suggested that abnormalities in calcium homeostasis may be involved in the development or exacerbation of psoriasis. However, so far there have only been two reports of pseudohypoparathyroidism associated with psoriasis. OBJECTIVE: To describe the familial occurrence of this association for the first time. CASE REPORTS: Two siblings with psoriasis associated with pseudohypoparathyroidism were presented. The first patient was a 24-year-old white male with disseminated erythrodermic pustular psoriasis that began 2 months before admission. He had had a history of mental retardation, recurrent otitis, seizures and arthralgia from the age of 11 years onwards. He presented the characteristic phenotype of Albright osteodystrophy: short stature, obesity, round facies, broad forehead, short neck and brachydactylia. He adopted a position of flexed limbs and showed proximal muscle weakness and a positive Trousseau sign. He had clinical signs of hypocalcemia (0.69 mmol/l ionized calcium and 3.2 mg/dl total calcium, hyperphosphatemia (6.6 mg/dl, hypomagnesemia (1.0 mEq/l, hypoalbuminemia (3.1 g/dl, normal serum intact PTH levels (45.1 pg/ml, primary hypothyroidism (13.2 mU/ml TSH, and 4.7 mg/dl total T4, hypergonadotrophic hypogonadism (116.0 ng/ml LH, 13.2 mU/ml FSH and 325.0 ng/dl testosterone, osteoporosis, and diffuse calcifications in soft tissues and in the central nervous system. The second case was a 14-year-old white girl with a history of psoriasis vulgaris from the age of five years onwards, and antecedents of mental retardation. She presented signs of Albright osteodystrophy (short stature, round facies, obesity, short neck, brachydactylia, hypocalcemia (ionized calcium of 1.08 mmol/l and total calcium of 6.7 mg/dl hyperphosphatemia (9.4 mg/dl, elevated serum PTH levels (223.0 pg/ml, osteoporosis, and hypergonadotrophic

  7. Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

    Science.gov (United States)

    Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

    2014-01-01

    Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck

  8. BRCA1/2 associated hereditary breast cancer

    Institute of Scientific and Technical Information of China (English)

    Li-song TENG; Yi ZHENG; Hao-hao WANG

    2008-01-01

    Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

  9. Acromegaly and McCune-Albright Syndrome

    Science.gov (United States)

    Salenave, Sylvie; Boyce, Alison M.; Collins, Michael T.

    2014-01-01

    Background: McCune-Albright syndrome (MAS) includes the triad of poly/monostotic fibrous dysplasia, café-au-lait spots, and hyperfunctioning endocrinopathies. Acromegaly affects around 20% of MAS patients. Aims: The objective was to review all reported cases of acromegaly associated with MAS. Methods: All studies and case reports of acromegaly in patients with MAS were systematically sought in the world literature up to January 2013. We also included new data (from three unreported cases) and updated data on 23 previously reported patients from our two centers. Results: We reviewed the cases of 112 patients (65 males). Mean age at diagnosis of acromegaly was 24.4 years (range, 3–64). Among the 40 pediatric patients, 23 (57%) had precocious puberty. GH/IGF-1 excess was suggested by accelerated growth in 85% of pediatric cases. Acromegaly was almost always associated with skull base fibrous dysplasia. Modern imaging techniques (computed tomography or magnetic resonance imaging) revealed an adenoma in 54% of the patients (macroadenoma in more than two-thirds). Median GH levels and mean IGF-1 SD score at diagnosis were 57 μg/L (2.8 to 291 μg/L) and 8 (2.3 to 24), respectively. Hyperprolactinemia was present in 81% (mean, 149 μg/L; range, 21–600). Pituitary surgery, performed in 25 cases, very rarely cured the GH/IGF-1 excess. Somatostatin analogs improved GH/IGF-1 levels in most patients but achieved control of acromegaly in only 17 (30%) of 56 patients. Pegvisomant achieved normal IGF-1 levels in 10 of 13 cases. Conclusion: Acromegaly, which is present in 20–30% of patients with MAS, raises particular diagnostic and therapeutic issues. PMID:24517150

  10. Startle responses in hereditary hyperekplexia

    NARCIS (Netherlands)

    Tijssen, M. A.; Voorkamp, L. M.; Padberg, G. W.; van Dijk, J. G.

    1997-01-01

    BACKGROUND: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of

  11. Startle responses in hereditary hyperekplexia

    NARCIS (Netherlands)

    Tijssen, MAJ; Voorkamp, LM; Padberg, GW; vanDijk, JG

    Background: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of

  12. Cellular characteristics of hereditary diseases of man

    International Nuclear Information System (INIS)

    Sasaki, Masao

    1978-01-01

    Hereditary diseases of which abnormal characters could be detected at cultured cell level were introduced, and tissue cultures of them were described. Characteristics such as reproduction, disorder, elimination, and repair of DNA in hereditary diseases with high cancer risk such as Bloom syndrome, etc. were investigated. Radiosensitivity of these hereditary diseases was also described, and factors of carcinogenesis were investigated. (Serizawa, K.)

  13. Hereditary angioedema

    Science.gov (United States)

    ... disease; HAE- Hereditary angioedema; Kallikrein inhibitor-HAE: bradykinin receptor antagonist-HAE; C1-inhibitors-HAE; Hives-HAE ... aunt, uncle, or grandparent. Dental procedures, sickness (including colds and the flu), and surgery may trigger HAE ...

  14. The molecular classification of hereditary endocrine diseases.

    Science.gov (United States)

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  15. Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Susumu Takamatsu

    2016-01-01

    Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

  16. Genetics Home Reference: hereditary hemorrhagic telangiectasia

    Science.gov (United States)

    ... Central OMIM: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic ... 10.1097/GIM.0b013e3182136d32. Review. Citation on PubMed McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead ...

  17. Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type

    Directory of Open Access Journals (Sweden)

    Kolokolova A.M.

    2016-09-01

    Full Text Available Aim: to study the value of routine methods (clinical symptoms, electrophysiological findings and results of DNA analysis in diagnostics of hereditary motor sensory neuropathy type IA in outpatient clinics. Material and Methods. The review of foreign literature is represented. The phenotypic polymorphism, genetic heterogeneity and the difficulties of diagnostics are identified. A family with hereditary motor sensory neuropathy of lAtype is presented, which was diagnosed on the base of available methods in outpatient practice (clinical symptoms, genealogical method, electro-physiological findings and DNA analysis results. Results. Routine algorithm (consistent valuation of clinical symptoms, neurophysiologic findings and the results of DNA analysis helped to verify the diagnosis of hereditary motor sensory neuropathy of lAtype in outpatient practice after more than 20 years of the onset of the disease. Conclusion. The neurologists of outpatient clinics and other specialists must be informed about the availability of diagnostics of hereditary diseases of nervous system.

  18. Bone scan appearance of renal osteodystrophy in diabetic chronic renal failure patients

    International Nuclear Information System (INIS)

    So, Young; Hyun, In Young; Lee, Dong Soo; Ahn, Curie; Chung, June-Key; Kim, Suhnggwon; Lee, Myung Chul; Lee, Jung Sang; Koh, Chang-Soon

    1998-01-01

    To investigate Tc-99m methylenediphosphonate (MDP) bone scan appearance in diabetic chronic renal failure patients, we compared the bone scan images of chronic renal failure patients with and without diabetes. The number of patients studied was 134, of whom 43 had diabetes. Two nuclear medicine physicians read Tc-99m MDP bone scan images and for six areas - the axial skeleton, long bone, skull and mandible, periarticular areas, costochondral junction, and sternum - assigned a score of either 1 or 0. The sums of scores were compared. We also performed multivariate analysis including sex, age, and serum creatinine level using analysis of covariance. DM group patients scored significantly lower (2.01±0.95) than those of the non-DM group (3.26±1.16). Analysis of covariance revealed that the lower DM group score was independent of sex, age, and serum creatinine level. The bone scans of diabetic chronic renal failure patients showed less Tc-99m MDP uptake than those of non-diabetic patients. Thus, diagnosing renal osteodystrophy in diabetic chronic renal failure patients on bone scan images could be difficult. (author)

  19. Genetics Home Reference: hereditary diffuse gastric cancer

    Science.gov (United States)

    ... Health Conditions Hereditary diffuse gastric cancer Hereditary diffuse gastric cancer Printable PDF Open All Close All Enable Javascript ... Diffuse Gastric Cancer MedlinePlus Encyclopedia: Gastric Cancer National Cancer ... Option Overview General Information from MedlinePlus ( ...

  20. Ampliación de la galería de arte Albright – Knox

    Directory of Open Access Journals (Sweden)

    Skidmore - Owings - Merrill, Arquitectos

    1963-06-01

    Full Text Available Owings and Merrill, architects. This new extension houses an exhibition hall, an auditorium seating 350 people, lecture rooms, services, dining room, and a club room. The modifications to the old building have provided space for the Education Department and the Library. The auditorium is enclosed with large grey glass panels, and enables the beautiful park scenery to be viewed from within. From the outside, however, these glass surfaces act as mirrors, and reflect the surrounding views. To prevent the sun from penetrating, black curtains have been fitted. The seats of the auditorium are covered with vermillion nylon cloth, and the floor has a light yellow carpet. The ground floor is constructed round an open air garden-court, which contains a number of sculptures, especially one by Henry Moore, and the Manipulator, by Reg Butler. Large glazed areas are a feature of the building surface round the garden-court. The buildings are connected with each other at the level of the ground floor, and we feel that the outstanding success of the Albright Knox Gallery is due to the surprising harmony achieved between the old and the new buildings.La nueva ampliación alberga: una sala de exposiciones, un auditorio con capacidad para 350 personas sentadas, salas de conferencias, servicios, comedor y estar-club. La renovación realizada en el edificio antiguo ha proporcionado espacios para el Departamento de educación y la biblioteca. El auditorio, cerrado con amplios cristales grises, permite a los visitantes del interior contemplar el bello paisaje del parque, mientras que en el exterior actúa como un espejo, que refleja los alrededores. Para impedir el paso de los rayos solares dispone de cortinas negras; los asientos están tapizados en nylon bermellón y el piso va cubierto con moquetas beige. La planta baja rodea, mediante espacios también acristalados, el patio-jardín al aire libre, dedicado a escultura, en el que destacan una de Henry Moore, y el

  1. Drug therapy for hereditary cancers

    Directory of Open Access Journals (Sweden)

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  2. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

  3. DESIGNING AND OPPORTUNITY FUEL WITH BIOMASS AND TIRE-DERIVED FUEL FOR COFIRING AT WILLOW ISLAND GENERATING STATION AND COFIRING SAWDUST WITH COAL AT ALBRIGHT GENERATING STATION

    Energy Technology Data Exchange (ETDEWEB)

    K. Payette; D. Tillman

    2004-06-01

    During the period July 1, 2000-March 31, 2004, Allegheny Energy Supply Co., LLC (Allegheny) conducted an extensive demonstration of woody biomass cofiring at its Willow Island and Albright Generating Stations. This demonstration, cofunded by USDOE and Allegheny, and supported by the Biomass Interest Group (BIG) of EPRI, evaluated the impacts of sawdust cofiring in both cyclone boilers and tangentially-fired pulverized coal boilers. The cofiring in the cyclone boiler--Willow Island Generating Station Unit No.2--evaluated the impacts of sawdust alone, and sawdust blended with tire-derived fuel. The biomass was blended with the coal on its way to the combustion system. The cofiring in the pulverized coal boiler--Albright Generating Station--evaluated the impact of cofiring on emissions of oxides of nitrogen (NO{sub x}) when the sawdust was injected separately into the furnace. The demonstration of woody biomass cofiring involved design, construction, and testing at each site. The results addressed impacts associated with operational issues--capacity, efficiency, and operability--as well as formation and control of airborne emissions such as NO{sub x}, sulfur dioxide (SO{sub 2}2), opacity, and mercury. The results of this extensive program are detailed in this report.

  4. Hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Vase, P; Green, A

    1999-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early...

  5. Hereditary spherocytosis: Consequences of delayed diagnosis

    Directory of Open Access Journals (Sweden)

    Sarah C Steward

    2014-08-01

    Full Text Available Objective: To determine whether patients with undiagnosed hereditary spherocytosis hospitalized for transfusions might have avoided hospitalization via earlier diagnosis. Study design: Charts of all (N = 30 patients with hereditary spherocytosis seen in pediatric hematology at West Virginia University-Charleston were reviewed. Family and transfusion history and presence of neonatal jaundice were recorded. Complete blood count and reticulocyte values during infancy were available for 20 of 30 patients, while baseline steady-state values were available for all 30. Results: Transfusions were given to 22 patients; 12 of 14 with an aplastic crisis were undiagnosed. In 10 of 12, the severity of anemia led to hospitalization (3 to intensive care. All 10 had prior mean corpuscular hemoglobin concentration and/or red cell distribution width elevations and a history of neonatal jaundice; 7 of 10 had a positive family history. Conclusions: Undiagnosed hereditary spherocytosis may lead to inpatient transfusions for severe anemia. Earlier detection of hereditary spherocytosis is easily achievable and may reduce hospitalizations via closer monitoring.

  6. Fibrous dysplasia and McCune–Albright syndrome: Imaging for positive and differential diagnoses, prognosis, and follow-up guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Bousson, Valérie, E-mail: valerie.bousson@lrb.aphp.fr [Radiologie Ostéo-Articulaire, AP-HP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris VII Denis Diderot, Sorbonne Paris Cité (France); Rey-Jouvin, Caroline, E-mail: c.reyjouvin@gmail.com [Rhumatologie Viggo Petersen, AP-HP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris VII Denis Diderot, Sorbonne Paris Cité (France); Laredo, Jean-Denis, E-mail: jean-denis.laredo@lrb.aphp.fr [Radiologie Ostéo-Articulaire, AP-HP, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris (France); Université Paris VII Denis Diderot, Sorbonne Paris Cité (France); Le Merrer, Martine, E-mail: martine.lemerrer@inserm.fr [Service de génétique médicale, AP-HP, Hôpital Necker – Enfants malades, 149 rue de Sèvres, 75743 Paris Cedex 15 (France); Martin-Duverneuil, Nadine, E-mail: nadine.martin-duverneuil@psl.aphp.fr [Service de Neuroradiologie, AP-HP, Hôpital Pitié Salpêtrière, 47 Boulevard de l’hôpital, 75013 Paris (France); and others

    2014-10-15

    Highlights: • The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). • Specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. • We believe the dissemination of these recommendations within the radiology community may substantially improve the management of patients with these rare but potentially disabling conditions. - Abstract: Purpose: The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). The development of a standardized approach to the management of FD/MAS is crucial given the low incidence and multiple clinical presentations of these conditions. Our aim was to develop recommendations for bone imaging in FD/MAS management. Materials and methods: The establishment of National Reference Centers in France as part of a Health Ministry program for orphan diseases has triggered the development of recommendations for the clinical management of FD/MAS. We used a well-established robust methodological approach involving an extensive literature review by a multidisciplinary working group (20 healthcare professionals) and scoring by a peer-review group (20 healthcare professionals different from the 20 previous ones). There were four phases: a systematic literature review, drafting of initial recommendations, peer-review of this initial draft, and drafting of the final recommendations. Results: Fifty-seven specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. Issues of special interest are highlighted in the discussion, and areas in which future research is needed are identified. Conclusion: We believe the dissemination of these recommendations within the radiology community may facilitate communication between radiologists and other healthcare

  7. Fibrous dysplasia and McCune–Albright syndrome: Imaging for positive and differential diagnoses, prognosis, and follow-up guidelines

    International Nuclear Information System (INIS)

    Bousson, Valérie; Rey-Jouvin, Caroline; Laredo, Jean-Denis; Le Merrer, Martine; Martin-Duverneuil, Nadine

    2014-01-01

    Highlights: • The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). • Specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. • We believe the dissemination of these recommendations within the radiology community may substantially improve the management of patients with these rare but potentially disabling conditions. - Abstract: Purpose: The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune–Albright syndrome (MAS). The development of a standardized approach to the management of FD/MAS is crucial given the low incidence and multiple clinical presentations of these conditions. Our aim was to develop recommendations for bone imaging in FD/MAS management. Materials and methods: The establishment of National Reference Centers in France as part of a Health Ministry program for orphan diseases has triggered the development of recommendations for the clinical management of FD/MAS. We used a well-established robust methodological approach involving an extensive literature review by a multidisciplinary working group (20 healthcare professionals) and scoring by a peer-review group (20 healthcare professionals different from the 20 previous ones). There were four phases: a systematic literature review, drafting of initial recommendations, peer-review of this initial draft, and drafting of the final recommendations. Results: Fifty-seven specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. Issues of special interest are highlighted in the discussion, and areas in which future research is needed are identified. Conclusion: We believe the dissemination of these recommendations within the radiology community may facilitate communication between radiologists and other healthcare

  8. Hereditary & familial colorectal cancer : Identification, characteristics, surveillance

    NARCIS (Netherlands)

    Kallenberg, F.G.J.

    2017-01-01

    Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history

  9. Radiological diagnosis of renal osteodystrophy with reference to clinical features in patients undergoing maintenance hemodialysis

    International Nuclear Information System (INIS)

    Huebsch, P.; Trattnig, S.; Barton, P.; Seidl, G.

    1989-01-01

    Pathophysiological, histological and radiological findings in renal osteodystrophy are described. Special emphasis is laid on secondary hyperparathyroidism. Preliminary results of the authors' investigations show a good correlation between radiological findings in the phalanges of the hand and the concentration of parathyroid hormone (PTH) in 14 patients. The concentration of the hormone in the blood was measured by a new 'two-site' immunoradiometric assay, which is specific for the intact, biologically active hormone. Patients with high concentrations of PTH in the blood tended to have more severe radiological changes. In 4 patients for whom radiographs of the hands revealed no pathologic findings, normal PTH concentrations in the blood were measured by this method, whereas the conventional assay gave elevated hormone concentrations for the same patients. This is due to the lack of specificity of the conventional method for the intact, biologically active hormone. Nevertheless, further investigations are needed to confirm these findings. (orig.) [de

  10. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

    Science.gov (United States)

    Giavina-Bianchi, Pedro; França, Alfeu T; Grumach, Anete S; Motta, Abílio A; Fernandes, Fátima R; Campos, Regis A; Valle, Solange O; Rosário, Nelson A; Sole, Dirceu

    2011-01-01

    Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  11. Studies of the skeletal pathophysiology of renal osteodystrophy using nucleomedical procedures

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Nobuaki (Kawasaki Medical School, Kurashiki, Okayama (Japan))

    1988-12-01

    Bone scintigraphy with Tc-99m labeled phosphorous compounds has been performed in a series of 160 long-term hemodialysis patients with chronic renal failure. Renal osteodystrophy (ROD) was classified by five features of RI uptake in the entire skeleton: type A (low turn-over type) - a relatively decreased RI uptake in the bone tissue and an increased uptake in the soft tissue; type C (normal type) - normal findings; type D (osteomalacia type) - a strong RI uptake in the costochondral joints; type F (hyperparathyroid type) - strong RI uptake in the skull and submandible; and type G (calcification type) - an ectopic calcification. The group of type F had elevated levels of both alkaline phosphatase (ALP) and parathyroid hormones (PTH); on the contrary, both ALP and PTH were decreased in the group of type A. This suggested an increased and decreased bone metabolism in type F and A, respectively. The group of type D was characterized by having hypophosphatemia. Pathophysiologic types of ROD varied from day to day. Bone mineral density (BMD) tended to decrease in the radius. For the spine, however, BMD increased in some cases and decreased in the other cases with prolonging the duration of hemodialysis. Bone scintigraphy and BMD determination in both the cortical and cavernous bone tissue may provide integrated information about ROD presenting with heterogeneity of the entire skeleton. (Namekawa, K).

  12. Genetics Home Reference: hereditary sensory neuropathy type IA

    Science.gov (United States)

    ... sensory neuropathy type IA Hereditary sensory neuropathy type IA Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in ...

  13. Clinical characterization and molecular classification of 12 Korean patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

    Science.gov (United States)

    Cho, S Y; Yoon, Y A; Ki, C-S; Huh, H J; Yoo, H-W; Lee, B H; Kim, G-H; Yoo, J-H; Kim, S-Y; Kim, S J; Sohn, Y B; Park, S W; Huh, R; Chang, M S; Lee, J; Kwun, Y; Maeng, S H; Jin, D-K

    2013-10-01

    Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP. A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP. All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib. Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  14. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Pedro Giavina-Bianchi

    2011-01-01

    Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  15. EAMJ Oct Hereditary.indd

    African Journals Online (AJOL)

    HEREDITARY GINGIVAL FIBROMATOSIS: REPORT OF FAMILY CASE SERIES. E. G. Wagaiyu ... Senior Lecturer, Department of Periodontology/Community and Preventive Dentistry, ... fibrous connective tissue held in chronically inflamed.

  16. Pituitary and ovarian abnormalities demonstrated by CT and ultrasound in children with features of the McCune-Albright syndrome

    International Nuclear Information System (INIS)

    Rieth, K.G.; Comite, F.; Shawker, T.H.; Cutler, G.B. Jr.

    1984-01-01

    In a random series of 97 children referred to the National Institutes of Health with a presumptive diagnosis of precocious puberty, eight girls were found to have features of the McCune-Albright syndrome, including fibrous dysplasia of bone and/or skin lesions resembling cafe au lait spots. Radiographic evaluation of these patients included computed tomography of the head and pelvic ultrasound. The pituitary glands were suspicious for abnormality in five of the eight girls. Seven girls underwent pelvic ultrasound, and in all of them the ovaries were considered to be abnormal for their chronological age; in addition, two had functional ovarian cysts. The role of diagnostic radiological studies in the diagnosis of this syndrome is discussed

  17. Learning about Hereditary Hemochromatosis

    Science.gov (United States)

    Skip to main content Learning About Hereditary Hemochromatosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  18. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  19. A Review of Hereditary Fructose Intolerance

    Directory of Open Access Journals (Sweden)

    Mogoş Tiberius

    2016-03-01

    Full Text Available Fructose intolerance is a metabolic disorder with hereditary determinism, clinically manifested on terms of fructose intake. Untreated, hereditary fructose intolerance may result in renal and hepatic failure. Unfortunately, there are no formal diagnostic and surveillance guidelines for this disease. If identified and treated before the occurrence of permanent organ damage, patients can improve their symptoms and self-rated health. Implementation and adherence to a strict fructose free diet is often difficult, but not impossible.

  20. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  1. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

    Directory of Open Access Journals (Sweden)

    Collins Michael T

    2012-05-01

    Full Text Available Abstract Fibrous dysplasia (FD is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS. The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues. The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.

  2. Hereditary Hearing Loss.

    Science.gov (United States)

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  3. Revisited diagnostics of hereditary epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    V. I. Albanova

    2014-01-01

    Full Text Available Hereditary epidermolysis bullosa is a big group of hereditary diseases with the main manifestations in the form of blisters on the skin and mucous coat after slight mechanical injuries. It is not always possible to diagnose this disease based on the clinical picture. The article discusses current laboratory diagnostics methods for hereditary epidermolysis bullosa including immunofluorescence antigen mapping (IFM, transmission electron microscopy (TEM and genetic analysis (molecular or DNA diagnostics as well as their advantages and disadvantages. TEM determines the micro splitting level and nature of ultrafine changes in the area of the dermoepidermal junction; at the same time, such tests need special expensive equipment. Substantial experience is also needed to analyze the resulting submicroscopic images. IFM determines whether expression of the affected protein related to the disease development is reduced or absent; however, invalid (false positive or false negative results can be obtained in patients with the reduced expression of the affected protein. Genetic analysis plays a key role for prenatal diagnostics. Therefore, to make an exact diagnosis of hereditary epidermolysis bullosa, it is expedient to apply IFM, TEM and genetic analysis. The need to set an exact diagnosis of the disease is related to the fact that the promising treatment methods being currently developed are aimed at treating patients with certain forms of the disease.

  4. Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Syed, I; Sunkaraneni, V S

    2015-05-01

    There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis. The Medline and Embase databases were interrogated on 15 November 2013 using the search items 'hereditary haemorrhagic telangiectasia' (title), 'epistaxis' (title) and 'treatment' (title and abstract), and limiting the search to articles published in English. A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3 in vitro studies. There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.

  5. Hereditary angioedema: a bradykinin-mediated swelling disorder.

    Science.gov (United States)

    Björkqvist, Jenny; Sala-Cunill, Anna; Renné, Thomas

    2013-03-01

    Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

  6. [Paediatric retinal detachment and hereditary vitreoretinal disorders].

    Science.gov (United States)

    Meier, P

    2013-09-01

    The number of retinal detachments in children is very low in comparison to the number in adults. One predisposing factor for development of paediatric retinal detachment is suffering from hereditary vitreoretinal degeneration (e.g., Stickler syndrome, Wagner syndrome, Kniest dysplasia, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, Knobloch syndrome, incontinentia pigmenti, Norrie disease). Hereditary vitreoretinopathies are characterised by an abnormal-appearing vitreous gel with associated retinal changes. In most of these eyes further ocular abnormalities can be diagnosed. A group of hereditary disorders is associated with characteristic systemic abnormalities. Allied conditions should be considered in the clinical diagnosis. Vitreoretinopathies are the most common cause of inherited retinal detachment. In most eyes primary vitrectomy is necessary, and disease-specific surgical treatment is discussed. Georg Thieme Verlag KG Stuttgart · New York.

  7. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    Science.gov (United States)

    ... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

  8. Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

    Directory of Open Access Journals (Sweden)

    Rajkumar T

    2005-11-01

    Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.

  9. Therapeutic Strategies for Hereditary Kidney Cancer.

    Science.gov (United States)

    Sidana, Abhinav; Srinivasan, Ramaprasad

    2016-08-01

    The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

  10. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

    NARCIS (Netherlands)

    Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Gómez García, Encarna; Ruijs, Mariëlle; Verhoef, Senno

    2009-01-01

    The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

  11. Squamous cell carcinoma complicating an hereditary epidermo-lysis bullosa

    International Nuclear Information System (INIS)

    Mseddi, M.; Turki, H.; Marrekchi, S.; Abdelmaksoud, W.; Masmoudi, A.; Bouassida, S.; Zahaf, A.

    2004-01-01

    The dystrophic form of hereditary epidermo-lysis bullosa is associated with an increased frequency of squamous cell carcinoma. We report a new case. An 18-year-old patient, carrying a Hallopeau Siemens hereditary epidermo-lysis bullosa, presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded with inguinal lymphadenopathy. The histological study ted to the conclusion of a well differentiated squamous cell carcinoma. The patient was treated surgically. Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the postoperative course was fatal due to an infection and to a deterioration of her general condition. Squamous cell carcinoma frequently occurs on the cicatricial lesion of hereditary epidermo-lysis bullosa and usually affects males with recessive hereditary epidermo-lysis bullosa. Metastases are frequent, precocious and multiple. The treatment may be surgical. The particularities of our observation are the young age of patient and the localization. (author)

  12. Hereditary Lymphedema of the Leg – A Case Report

    Directory of Open Access Journals (Sweden)

    Birgit Heinig

    2017-07-01

    Full Text Available Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist when he was seven years old. He had never been treated for lymphedema but experienced multiple erysipelas during his life. After diagnostic procedures to exclude other causes of leg swelling, the diagnosis of hereditary lymphedema of the leg, stage III was confirmed. We initialized complex decongestive therapy. During two weeks of intensive treatment, the circumference of the left leg could be reduced by 10 cm. This case illustrates the "natural course" hereditary lymphedema. But it raises the hope that even after decades of ignorance, the patients benefits from complex decongestive treatment. Therapeutic nihilism is unnecessary and poses lymphedema patients to risks of infection and secondary malignancies like Stewart-Trewes syndrome.

  13. The prevalence of depression in hereditary spastic paraplegia.

    Science.gov (United States)

    Vahter, L; Braschinsky, M; Haldre, S; Gross-Paju, K

    2009-09-01

    To evaluate the prevalence of depression and sensitivity and specificity of the single-item interview 'Are you depressed?' for people with hereditary spastic paraplegia in Estonia. Single-item interview 'Are you depressed?' was used as a screening question for depression; all participants then completed the Beck Depression Inventory. People with hereditary spastic paraplegia identified from the epidemiological database who agreed to participate in the study. Beck Depression Inventory, clinical interview. The epidemiological database consisted of 59 patients with clinically confirmed diagnosis of hereditary spastic paraplegia. Forty-eight of these consented to participate in the study. The Beck Depression Inventory score was higher than cut-off point in 58% (28/48) and lower in 42% (20/48). Of the study group, 44% (21/48) had mild, 13% (6/48) moderate and one person revealed severe depression. There was a statistically significant correlation between Beck Depression Inventory score and level of mobility; no other significant correlations with other measures were detected. Of the participants, 54% (26/48) had subjective complaints about depression and answered 'Yes' to the single-item interview 'Are you depressed?'. The sensitivity of the one-item interview in the hereditary spastic paraplegia group was 75% and specificity 75%. Our results show that mild depression is prevalent among people with hereditary spastic paraplegia. Although the single question may be helpful, it cannot be relied upon entirely when assessing a person for depression.

  14. Hereditary and non-hereditary microangiopathies in the young. An up-date.

    Science.gov (United States)

    Ringelstein, E Bernd; Kleffner, Ilka; Dittrich, Ralf; Kuhlenbäumer, Gregor; Ritter, Martin A

    2010-12-15

    In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Knowledge regarding basic concepts of hereditary cancers, and the ...

    African Journals Online (AJOL)

    Background. In families with hereditary cancer, at-risk individuals can benefit from genetic counselling and testing. General practitioners (GPs) are ideally placed to identify such families and refer them appropriately. Objective. To assess the practices, knowledge and attitudes of GPs regarding common hereditary cancers.

  16. Hereditary periodic fever syndromes

    NARCIS (Netherlands)

    McDermott, MF; Frenkel, J

    Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

  17. Bone metabolic activity measured with positron emission tomography and [18F] fluoride ion in renal osteodystrophy: Correlation with bone histomorphometry

    International Nuclear Information System (INIS)

    Messa, C.; Goodman, W.G.; Hoh, C.K.; Choi, Y.; Nissenson, A.R.; Salusky, I.B.; Phelps, M.E.; Hawkins, R.A.

    1993-01-01

    The authors evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [ 18 F] fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [ 18 F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P 18 F] fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystropy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data

  18. Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

    Science.gov (United States)

    Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

    2002-01-01

    Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

  19. Hereditary familial vestibular degenerative diseases.

    NARCIS (Netherlands)

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    Identification of genes involved in hereditary vestibular disease is growing at a remarkable pace. Mutant mouse technology can be an important tool for understanding the biological mechanism of human vestibular diseases.

  20. Disease expression in women with hereditary angioedema

    DEFF Research Database (Denmark)

    Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle

    2008-01-01

    OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT p......-sensitive phenotype for some patients. CONCLUSION: The course of angioedema in women with C1 inhibitor deficiency is affected by physiologic hormonal changes; consequently, physicians should take these into account when advising on management.......OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills...

  1. Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

    Science.gov (United States)

    Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

    2011-09-01

    Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

  2. Open-heart surgery using a centrifugal pump: a case of hereditary spherocytosis.

    Science.gov (United States)

    Matsuzaki, Yuichi; Tomioka, Hideyuki; Saso, Masaki; Azuma, Takashi; Saito, Satoshi; Aomi, Shigeyuki; Yamazaki, Kenji

    2016-08-26

    Hereditary spherocytosis is a genetic, frequently familial hemolytic blood disease characterized by varying degrees of hemolytic anemia, splenomegaly, and jaundice. There are few reports on adult open-heart surgery for patients with hereditary spherocytosis. We report a rare case of an adult open-heart surgery associated with hereditary spherocytosis. A 63-year-old man was admitted for congestive heart failure due to bicuspid aortic valve, aortic valve regurgitation, and sinus of subaortic aneurysm. The family history, the microscopic findings of the blood smear, and the characteristic osmotic fragility confirmed the diagnosis of hereditary spherocytosis. Furthermore, splenectomy had not been undertaken preoperatively. The patient underwent a successful operation by means of a centrifugal pump. Haptoglobin was used during the cardiopulmonary bypass, and a biological valve was selected to prevent hemolysis. No significant hemolysis occurred intraoperatively or postoperatively. There are no previous reports of patients with hereditary spherocytosis, and bicuspid aortic valve. We have successfully performed an adult open-heart surgery using a centrifugal pump in an adult patient suffering from hereditary spherocytosis and bicuspid aortic valve.

  3. Hereditary lymphedema of the leg – A Case Report

    NARCIS (Netherlands)

    Heinig, Birgit; Lotti, T.; Tchernev, Georgi; Wollina, Uwe

    2017-01-01

    Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist) when he was seven years old. He had never been treated for lymphedema but

  4. Diagnosis and management of hereditary hemochromatosis.

    Science.gov (United States)

    Salgia, Reena J; Brown, Kimberly

    2015-02-01

    Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. New treatments of hereditary blindness

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Rosenberg, Thomas; Larsen, Michael

    2013-01-01

    Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a structura......Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life...... and a structurally intact retinal tissue to adult life with a complete loss of photoreceptors. It must be assumed that some of the trials will succeed in producing new therapies and action must be taken to refine and accelerate diagnostics and to preserve therapeutic potential in blind people....

  6. Hereditary breast cancer: from molecular pathology to tailored therapies.

    Science.gov (United States)

    Tan, D S P; Marchiò, C; Reis-Filho, J S

    2008-10-01

    Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

  7. Pes cavus and hereditary neuropathies: when a relationship should be suspected.

    Science.gov (United States)

    Piazza, S; Ricci, G; Caldarazzo Ienco, E; Carlesi, C; Volpi, L; Siciliano, G; Mancuso, M

    2010-12-01

    The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a "spy sign," discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases.

  8. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Hofstra, Robert M. W.

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

  9. [Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China].

    Science.gov (United States)

    2018-01-23

    Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.

  10. Hereditary hemochromatosis: An opportunity for gene therapy

    Directory of Open Access Journals (Sweden)

    FERNANDO EZQUER

    2006-01-01

    Full Text Available Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1 transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytes

  11. RECRUITMENT OF PATIENTS WITH HEREDITARY HAEMOCHROMATOSIS AS BLOOD DONORS

    Directory of Open Access Journals (Sweden)

    Marko Cukjati

    2004-12-01

    Full Text Available Background. Hereditary haemochromatosis is the most common inherited disorder in white persons with prevalence of about 1 in 200. Therapeutic phlebotomy is an effective treatment for the disease and prevents its sequele. In addition to their altruism, patients with hereditary haemochromatosis have also medical and monetary incentives for blood donation. Current guidelines do not allow haemochromatosis patients to donate blood. About two thirds of patients are eligible as blood donors and about two thirds of therapeutically drawn blood is suitable for transfusion. Therapeutically drawn blood could increase the blood supply by 1.5 to 30%.Conclusions. The number of states that already accept patients with hereditary haemochromatosis as blood donors is increasing. To avoid monetary incentives they offer free phlebotomies for all patients with hereditary haemochromatosis. There have been no reports about higher incidence of transfusion reactions. In Slovenia the number of therapeutic phlebotomy is increasing. We should evaluate the possibilities for recruitment of haemochromatosis patients as blood donors also in our country. It is necessary to modify regulatory restrictions and to ensure that there is no other incentives than altruism for blood donation.

  12. Genetics and ionizing radiations. 1. Genetics and hereditary diseases

    International Nuclear Information System (INIS)

    Dutrillaux, B.

    1980-01-01

    The desoxyribonucleic acid (DNA) is the chemical vehicle of heredity. Each hereditary character is determined by a short segment of the DNA molecule called gene. Gene operations are governed by regulating systems. The DNA is located in the chromosomes, easily analysed by light microscopy. The chromosome number and form are fairly characteristic of a species. Ours has 46 chromosomes, i.e. 23 pairs. Anomalies of the hereditary stock can be qualitative: affecting one gene they are expressed by diversely serious diseases. They can be quantitative and bear on the lack or excess of a chromosome or a segment of chromosome; most often, resulting diseases are very serious; Downs's syndrome is a well-known example. The various modes of transmission of these hereditary characters are analysed. The change of a chromosome or a gene from a normal to an abnormal form is called a mutation. It occurs scarcely, but the effects of mutations accumulate. At birth, nearly 10% of children should have one abnormal hereditary character at least, however most of these characters do not induce a true disease. Anomalies are more frequent at conception, many abnormal embryos or foetuses being aliminated by miscarriages [fr

  13. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  14. Hereditary myopathies with early respiratory insufficiency in adults.

    Science.gov (United States)

    Naddaf, Elie; Milone, Margherita

    2017-11-01

    Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

  15. Hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2015-03-01

    Full Text Available Hereditary hemochromatosis (HH is the most commonly identified autosomal recessive genetic disorder in the white population, characterized by increased intestinal iron absorption and secondary abnormal accumulation in parenchymal organs, not infrequently accompanied by functional impairment. This entity is associated with mutations of the HFE gene (located on the short arm of chromosome 6 at location 6p22.2; closely linked to the HLA-A3 locus, which encodes the HFE protein, a membrane protein thought to regulate iron absorption by affecting the interaction between transferrin receptor and transferrin.

  16. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Directory of Open Access Journals (Sweden)

    Ling-Chao Meng

    2015-01-01

    Full Text Available Background: Mutations of transthyretin (TTR cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

  17. Advances and challenges in hereditary cancer pharmacogenetics.

    Science.gov (United States)

    Cascorbi, Ingolf; Werk, Anneke Nina

    2017-01-01

    Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Moreover, the association between genetic variants of drug transporters with the clinical outcome is comprehensively discussed. Expert opinion: Precision therapy in the field of oncology is developing tremendously. There are a number of somatic tumor genetic markers that are indicative for treatment with anti-cancer drugs. By contrast, for some hereditary variants, recommendations have been developed. Although we have vast knowledge on the association between drug transporter variants and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. Further developments in research may lead to the discovery of rare, but functionally relevant single nucleotide polymorphisms and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.

  18. Genetics Home Reference: hereditary hypophosphatemic rickets

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... families, hereditary hypophosphatemic rickets has had an autosomal dominant inheritance pattern, which means one copy of an ...

  19. Hereditary History Preserving Bisimilarity Is Undecidable

    DEFF Research Database (Denmark)

    Jurdzinski, Marcin; Nielsen, Mogens

    2000-01-01

    History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement...

  20. New forms of -compactness with respect to hereditary classes

    Directory of Open Access Journals (Sweden)

    Abdo Mohammed Qahis

    2019-01-01

    Full Text Available A hereditary class on a set X is a nonempty collection of subsets closed under heredity. The aim of this paper is to introduce and study strong forms of u-compactness in generalized topological spaces with respect to a hereditary class, called  SuH-compactness and S- SuH-compactness. Also several of their properties are presented. Finally some eects of various kinds of functions on them are studied.

  1. Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in Shanghai, China.

    Science.gov (United States)

    Gan, Dekang; Li, Mengwei; Wu, Jihong; Sun, Xinghuai; Tian, Guohong

    2017-01-01

    To evaluate the clinical classification and characteristics of hereditary optic neuropathy patients in a single center in China. Retrospective case study. Patients diagnosed with hereditary optic neuropathy between January 2014 and December 2015 in the neuro-ophthalmology division in Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical features as well as visual field, brain/orbital MRI, and spectrum domain optical coherence tomography (SD-OCT) were analyzed. Eighty-two patients diagnosed by gene test were evaluated, including 66 males and 16 females. The mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with optic nerve atrophy, respectively. Leber hereditary optic neuropathy is the most common detected type of hereditary optic neuropathy in Shanghai, China. The detection of other autosomal mutations in hereditary optic neuropathy is limited by the currently available technique.

  2. Clinical features of Hereditary Haemorrhagic Telangiectasia

    NARCIS (Netherlands)

    Hosman, A.E.

    2017-01-01

    Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease (ROW), is an autosomal dominant disease with multi-systemic vascular dysplasia characterized by mucocutaneous telangiectasia, arteriovenous malformations and recurrent spontaneous epistaxis (nosebleeds). Most cases

  3. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  4. Genetics Home Reference: hereditary hemochromatosis

    Science.gov (United States)

    ... Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in ... about the genes associated with hereditary hemochromatosis HAMP HFE HJV PNPLA3 SLC40A1 TFR2 Related Information What is a gene? What is a gene mutation and how do ...

  5. Hereditary pituitary hyperplasia with infantile gigantism.

    Science.gov (United States)

    Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

    2011-12-01

    We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

  6. Effect of behavioral stage-based nutrition education on management of osteodystrophy among hemodialysis patients, Lebanon.

    Science.gov (United States)

    Karavetian, Mirey; de Vries, Nanne; Elzein, Hafez; Rizk, Rana; Bechwaty, Fida

    2015-09-01

    Assess the effect of intensive nutrition education by trained dedicated dietitians on osteodystrophy management among hemodialysis patients. Randomized controlled trial in 12 hospital-based hemodialysis units equally distributed over clusters 1 and 2. Cluster 1 patients were either assigned to usual care (n=96) or to individualized intensive staged-based nutrition education by a dedicated renal dietitian (n=88). Cluster 2 patients (n=210) received nutrition education from general hospital dietitians, educating their patients at their spare time from hospital duties. Main outcomes were: (1) dietary knowledge(%), (2) behavioral change, (3) serum phosphorus (mmol/L), each measured at T0 (baseline), T1 (post 6 month intervention) and T2 (post 6 month follow up). Significant improvement was found only among patients receiving intensive education from a dedicated dietitian at T1; the change regressed at T2 without statistical significance: knowledge (T0: 40.3; T1: 64; T2: 63) and serum phosphorus (T0: 1.79; T1: 1.65; T2: 1.70); behavioral stages changed significantly throughout the study (T0: Preparation, T1: Action, T2: Preparation). The intensive protocol showed to be the most effective. Integrating dedicated dietitians and stage-based education in hemodialysis units may improve the nutritional management of patients in Lebanon and countries with similar health care systems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Immunophenotyping of hereditary breast cancer

    NARCIS (Netherlands)

    van der Groep, P.

    2009-01-01

    Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

  8. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  9. The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

    2016-11-01

    Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q 2cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

  10. Hereditary rickets. How genetic alterations explain the biochemical and clinical phenotypes.

    Science.gov (United States)

    Papadopoulou, Anna; Gole, Evaggelia; Nicolaidou, Polyxeni

    2013-12-01

    The reemergence of vitamin D deficiency in the industrialized countries resurrects the "threat" of nutritional rickets, especially among pediatric populations, a fact that may lead to underdiagnosis of hereditary rickets. Today, hereditary rickets may be subdivided into two main groups according to their biochemical profile: the one associated with defects in vitamin D synthesis and action and the second associated with abnormal phosphorus metabolism. The classification of the patients in a particular group of hereditary rickets is determinative of the treatment to follow. This review, through the recent advances on vitamin D and P metabolism, discusses the molecular and biochemical defects associated to each group of inherited rickets, as well as the clinical phenotypes and the recommended therapeutic approaches.

  11. Hereditary noetherian prime rings and idealizers

    CERN Document Server

    Levy, Lawrence S

    2011-01-01

    The direct sum behaviour of its projective modules is a fundamental property of any ring. Hereditary Noetherian prime rings are perhaps the only noncommutative Noetherian rings for which this direct sum behaviour (for both finitely and infinitely generated projective modules) is well-understood, yet highly nontrivial. This book surveys material previously available only in the research literature. It provides a re-worked and simplified account, with improved clarity, fresh insights and many original results about finite length modules, injective modules and projective modules. It culminates in the authors' surprisingly complete structure theorem for projective modules which involves two independent additive invariants: genus and Steinitz class. Several applications demonstrate its utility. The theory, extending the well-known module theory of commutative Dedekind domains and of hereditary orders, develops via a detailed study of simple modules. This relies upon the substantial account of idealizer subrings wh...

  12. Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2015-01-01

    Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

  13. MRI in Leber's hereditary optic neuropathy

    DEFF Research Database (Denmark)

    Matthews, Lucy; Enzinger, Christian; Fazekas, Franz

    2015-01-01

    BACKGROUND: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological...

  14. Hereditary Gigantism-the biblical giant Goliath and his brothers.

    Science.gov (United States)

    Donnelly, Deirdre E; Morrison, Patrick J

    2014-05-01

    The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members' battles with David and his relatives.

  15. Descriptive Epidemiology, Molecular Biology and Genetics of Hereditary Prostate Cancer in Denmark

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen

    2012-01-01

    A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....

  16. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Bowen Tom

    2010-07-01

    Full Text Available Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010. Methods The Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'angioédème héréditaire (RCAH http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

  17. Genetics 101 --The Hereditary Material of Life

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

  18. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.

    1996-01-01

    Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within

  19. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    NARCIS (Netherlands)

    Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM

    Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of

  20. McCune-Albright syndrome, natural history and multidisciplinary management in a series of 14 pediatric cases.

    Science.gov (United States)

    Agopiantz, Mikael; Journeau, Pierre; Lebon-Labich, Béatrice; Sorlin, Arthur; Cuny, Thomas; Weryha, Georges; Leheup, Bruno

    2016-02-01

    McCune-Albright syndrome is a rare disorder characterized by endocrine disorders, café-au-lait spots and fibrous dysplasia of bone that occurs early in life. A series of 14 pediatric cases were followed between 1994 and 2013 by the competence center for rare endocrine diseases and constitutional bone diseases at CHU de Nancy (France). The diagnosis is based on the presence of at least two symptoms. The mean follow-up was 6 years (1-17 years). The sex ratio was six girls per boy. The incidence was 0.28 cases/million population/year. Mean age at diagnosis was 6 years. A mutation in the GNAS gene was found in 33% of patients tested. Gonadal involvement (13/14 cases), including early peripheral puberty and ovarian cysts in girls (82%) occurred on average at 4 years of age. Bone involvement (10/14 cases) appeared on average at 5 years of age and was most often multiple (80%) with fracture risk, and the skull, with a neurosensory risk. Clinical definition and methods of screening and monitoring can be improved to allow for an earlier intervention. It must be multidisciplinary and take into account the disability and quality of life of the patient. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Management of acute attacks of hereditary angioedema: potential role of icatibant

    Directory of Open Access Journals (Sweden)

    Hilary J Longhurst

    2010-09-01

    Full Text Available Hilary J LonghurstDepartment of Immunology, Barts and The London NHS Trust, London, UKAbstract: Icatibant (Firazyr® is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema.Keywords: hereditary angioedema, bradykinin, icatibant, C1 inhibitor deficiency

  2. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

    Directory of Open Access Journals (Sweden)

    Luciano Mesquita Simão

    2012-08-01

    Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  3. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families.

    NARCIS (Netherlands)

    Vos tot Nederveen Cappel, W.H. de; Nagengast, F.M.; Griffioen, G.; Menko, F.H.; Taal, B.G.; Kleibeuker, J.H.; Vasen, H.F.

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  4. Surveillance for hereditary nonpolyposis colorectal cancer - A long-term study on 114 families

    NARCIS (Netherlands)

    Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  5. Development of hypertrophic osteodystrophy and antibody response in a litter of vaccinated Weimaraner puppies.

    Science.gov (United States)

    Harrus, S; Waner, T; Aizenberg; Safra, N; Mosenco, A; Radoshitsky, M; Bark, H

    2002-01-01

    Two different vaccination protocols were compared with regard to the development of hypertrophic osteodystrophy (HOD) (also termed metaphyseal osteopathy) and effectiveness of immunisation in a litter of 10 Weimaraner puppies. Five puppies (group 1) were vaccinated with a modified live canine parvovirus vaccine (CPV) and then two weeks later with a trivalent vaccine containing modified live canine distemper virus and adenovirus type 2 combined with a Leptospira bacterin (DHL). The CPV and DHL vaccine protocols were administered a further two times, at two-week intervals. Group 2 was vaccinated with three consecutive multivalent vaccines containing modified live canine distemper virus, canine parvovirus, parainfluenza and adenovirus type 2 combined with a Leptospira bacterin, at four-week intervals. All puppies were first vaccinated at the age of eight weeks. Three dogs in group 1 developed HOD, while all five dogs in group 2 developed HOD during the study period. Dogs in group 2 had more episodes of HOD than those in group 1. Dogs in group 1 developed higher antibody titres to canine distemper virus and parvovirus compared with those in group 2. Only two out of the 10 dogs developed protective antibody titres to parvovirus. The results of this study suggest that the two different vaccination protocols affected the pattern of appearance of HOD and immunisation in this litter of Weimaraner puppies. The results obtained and the previously reported data suggest that a larger controlled study is needed to further elucidate the effect of different vaccination protocols on HOD and immunisation in Weimaraner puppies.

  6. The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands

    NARCIS (Netherlands)

    Vasen, H. F.; Offerhaus, G. J.; den Hartog Jager, F. C.; Menko, F. H.; Nagengast, F. M.; Griffioen, G.; van Hogezand, R. B.; Heintz, A. P.

    1990-01-01

    The hereditary colonic cancer syndrome without polyposis, hereditary non-polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site-specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II).

  7. [The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

    Science.gov (United States)

    He, J X; Jiang, Y F

    2017-08-06

    Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

  8. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    DEFF Research Database (Denmark)

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette

    2010-01-01

    ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 ...

  9. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

    2016-01-01

    OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a...

  10. The prevalence of primary hereditary hemochromatosis in central Anatolia.

    Science.gov (United States)

    Karaca, Halit; Güven, Kadri; Önal, Müge; Gürsoy, Şebnem; Başkol, Mevlüt; Özkul, Yusuf

    2013-01-01

    Hereditary hemochromatosis is an autosomal recessive disorder associated with the HFE genes. Early identification and diagnosis is important as end stage organ damage may occur if treatment is delayed.. This study aimed to identify the prevalence of hereditary hemochromatosis in Kayseri and surroundings known as Central Anatolia. 2304 participants (1220 males, 1084 females) who were older then the age of 17 were included in the study conducted between December 2005 and December 2006 in Kayseri, Turkey. Transferin saturation was measured from overnight fasting blood samples. Serum iron, total iron binding capacity, and transferin saturation were measured. Serum ferritin levels and hereditary hemochromatosis genetic analysis were also performed after an overnight fasting blood samples from participants whose transferin saturation results were more than 50% in man and more than 45% in women. The homozygote C282Y mutation and heterozygote C282Y mutation prevalences were found as 0.08% (1/1220) and 0.08% (1/1220) in male participants, respectively. The heterozygote H63D mutation prevalence was found in 0.09% (1/1084) of female participants. Calculated prevalences in general population are as follows; The homozygote C282Y mutation prevalence is 0.043% (1/2304), the heterozygote C282Y mutation prevalence is 0.043% (1/2304) and the heterozygote H63D mutation prevalence is 0.043% (1/2304). The prevalence of hereditary hemochromatosis in Central Anatolia is 0.043% (1/2304). Because of the relatively low frequency, population screening studies are not cost-effective.

  11. Intragenic Duplication A Novel Mutational Mechanism in Hereditary Pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, M. T.; Geisz, A.; Brusgaard, K.

    2011-01-01

    OBJECTIVES: In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide...... pancreatitis. The accelerated activation of p.K23_I24insIDK by cathepsin B is a unique biochemical property not found in any other pancreatitis-associated trypsinogen mutant. In contrast, the robust autoactivation of the novel mutant confirms the notion that increased autoactivation is a disease......-relevant mechanism in hereditary pancreatitis....

  12. Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Chang, Joseph; Yung, Katherine C

    2014-11-01

    This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

  13. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

  14. Hereditary chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  15. Major and minor form of hereditary hyperekplexia

    NARCIS (Netherlands)

    Tijssen, MAJ; Vergouwe, MN; van Dijk, JG; Rees, M; Frants, RR; Brown, P

    Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied

  16. Hereditary hemorrhagic telangiectasia clinical and molecular genetics

    NARCIS (Netherlands)

    Letteboer, T.G.W.

    2010-01-01

    Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber (ROW) syndrome is an autosomal dominant disease characterized by vascular malformations in multiple organ systems. HHT has an age-related penetrance and variable clinical expression. The clinical symptoms are caused by direct

  17. Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass.

    Science.gov (United States)

    Nguyen, Kevin A; Syed, Jamil S; Shuch, Brian

    2017-05-01

    The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    International Nuclear Information System (INIS)

    Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

    2014-01-01

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  19. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    Energy Technology Data Exchange (ETDEWEB)

    Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

    2014-03-15

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  20. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack...

  1. Bisphosphonate-induced zebra lines in fibrous dysplasia of bone: histo-radiographic correlation in a case of McCune-Albright syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Corsi, Alessandro; Riminucci, Mara [Sapienza University, Department of Molecular Medicine, Rome (Italy); Ippolito, Ernesto [University of Rome Tor Vergata, Department of Orthopaedic Surgery, Rome (Italy); Robey, Pamela G. [Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (United States); Boyde, Alan [Queen Mary University of London, Dental Physical Sciences, London (United Kingdom)

    2017-10-15

    Bisphosphonates (BPs) are currently used in the treatment of diverse bone diseases including fibrous dysplasia of bone (FD). In pediatric patients, a radiographic consequence of cyclical administration of BPs is the development of apo-, epi-, and meta-physeal sclerotic bands, otherwise known as zebra lines, which result from the temporary inhibition of osteoclastic activity at the time of drug treatment. We report here on a child with McCune-Albright syndrome (FD in addition to hyperfunctioning endocrinopathies and skin hyperpigmentation) treated with cyclical intravenous infusions of pamidronate in which conventional radiography, contact microradiography, histology, and backscattered electron image analysis demonstrated that zebra lines formed only where bone was normal, were arrested at the boundary between FD-unaffected and FD-affected bone where bone is sclerotic, and were absent within the undermineralized FD bone. Moreover, in spite of the treatment, the FD lesions continued to expand. This case report is unique because no previously published studies correlated the radiographic and the histologic features of BP-induced zebra lines in the metaphysis of an FD-affected long bone of the limbs. (orig.)

  2. Bisphosphonate-induced zebra lines in fibrous dysplasia of bone: histo-radiographic correlation in a case of McCune-Albright syndrome

    International Nuclear Information System (INIS)

    Corsi, Alessandro; Riminucci, Mara; Ippolito, Ernesto; Robey, Pamela G.; Boyde, Alan

    2017-01-01

    Bisphosphonates (BPs) are currently used in the treatment of diverse bone diseases including fibrous dysplasia of bone (FD). In pediatric patients, a radiographic consequence of cyclical administration of BPs is the development of apo-, epi-, and meta-physeal sclerotic bands, otherwise known as zebra lines, which result from the temporary inhibition of osteoclastic activity at the time of drug treatment. We report here on a child with McCune-Albright syndrome (FD in addition to hyperfunctioning endocrinopathies and skin hyperpigmentation) treated with cyclical intravenous infusions of pamidronate in which conventional radiography, contact microradiography, histology, and backscattered electron image analysis demonstrated that zebra lines formed only where bone was normal, were arrested at the boundary between FD-unaffected and FD-affected bone where bone is sclerotic, and were absent within the undermineralized FD bone. Moreover, in spite of the treatment, the FD lesions continued to expand. This case report is unique because no previously published studies correlated the radiographic and the histologic features of BP-induced zebra lines in the metaphysis of an FD-affected long bone of the limbs. (orig.)

  3. Hereditary Angioedema in Childhood

    DEFF Research Database (Denmark)

    Kjaer, Line; Bygum, Anette

    2012-01-01

    Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of r...... of recurrent skin swellings and abdominal pain leading to several hospital admissions. The aim of this report is to direct focus on this rare disease, which can be treated effectively, to diminish morbidity and mortality of children suffering from undiagnosed HAE....

  4. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  5. The molecular basis of hereditary enamel defects in humans.

    Science.gov (United States)

    Wright, J T; Carrion, I A; Morris, C

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. © International & American Associations for

  6. The Molecular Basis of Hereditary Enamel Defects in Humans

    Science.gov (United States)

    Carrion, I.A.; Morris, C.

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. PMID:25389004

  7. Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

    DEFF Research Database (Denmark)

    Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won

    2006-01-01

    PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...

  8. Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support.

    Science.gov (United States)

    den Heijer, Mariska; Seynaeve, Caroline; Vanheusden, Kathleen; Duivenvoorden, Hugo J; Bartels, Carina C M; Menke-Pluymers, Marian B E; Tibben, Aad

    2011-12-01

    Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.

  9. X-ray criteria of the differential diagnosis of hereditary tubulopathies in children

    International Nuclear Information System (INIS)

    Bosin, V.Yu.; Kondrina, V.V.; Mulyk, T.E.; Verbitskaya, A.I.

    1995-01-01

    In search for x-ray signs of skeletal involvement specific for each type of hereditary tubulopathies Vitamin D-resistant rickets, Renal tubular acidosis, Toni-Debre-Fanconi disease, the authors analyze the results of clinical and X-ray examinations of 144 children aged 2 to 16. Study demonstrated the possibility and high reliability of X-ray differential diagnosis of various forms of hereditary tubulopathies in children. 5 refs., 8 figs., 2 tabs

  10. Spinal Exostosis in a Boy with Multiple Hereditary Exostoses

    Directory of Open Access Journals (Sweden)

    Ali Al Kaissi

    2013-01-01

    Full Text Available We report on a 13-year-old boy who presented with multiple hereditary exostosis and had development of back pain, associated with neurological deficits, and was found to have exostoses in the spinal canal. Spine radiograph showed a cauliflower-like abnormality of multiple exostoses of the posterior arch (pedicle of the thoracic vertebrae (T3–5. Reformatted CT scanning revealed the simultaneous development of intra- and extraspinal osteochondromatosis of T3–5. The spinal cord was compressed by the intraspinal exostosis. Our patient was surgically treated for intraspinal exostoses and showed cessation of neurological deficits. We report what might be a rare association of spinal cord compression in a patient with multiple hereditary exostoses.

  11. Ventricular assist device implantation in a young patient with non-compaction cardiomyopathy and hereditary spherocytosis.

    Science.gov (United States)

    Huenges, Katharina; Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

    2018-04-01

    A case of a 15-year-old female patient with acute heart failure due to non-compaction cardiomyopathy and hereditary anaemia (hereditary spherocytic elliptocytosis) requiring ventricular assist device implantation as a bridge to transplantation is presented. The possible effects of mechanical stress on erythrocytes potentially induced by mechanical circulatory support remains unclear, but it may lead to haemolytic crisis in patients suffering from hereditary anaemia. In our case, ventricular assist device therapy was feasible, and haematological complications did not occur within 6 weeks of bridging our patient to heart transplantation.

  12. Pavlodar city children's some hereditary diseases

    International Nuclear Information System (INIS)

    Shajmardanova, B. Kh.; Gorbach, S.V.

    1997-01-01

    Territory of the Pavlodar region directly adjoining to the Semipalatinsk test site is unique object for study of many year tests consequences on population health. Health worsening caused by small doses of radiation on artificial pollution background is defined. Purpose of the work is Pavlodar city children's some hereditary diseases (Downs syndrome, crack of upper lip and/or palate, hemophilia) under study of frequency dynamic of statistical data within period from 1980 by 1995. It is defined: a) tendency to growth Downs syndrome frequency has been distinctly observed beginning of the 1982; b) it is noted Downs syndrome frequency growth stabilization within period from 1988 by 1991; c) among children with Downs syndrome is distinguished low viability; d) there is rather higher correlation rate of Downs syndrome and congenial heart threshold against average statistical index; e) character of frequencies changes of crack of upper lip and/or palate has tendency to growth; f) it is defined that boys predominate among children with this disease; g) congenial crack of soft palate have being revealed as solitary thresholds of development; h) genealogy analysis of hemophilia sick reveals, that it has only hereditary character. 8 refs

  13. Molecular biology of hereditary diabetes insipidus.

    Science.gov (United States)

    Fujiwara, T Mary; Bichet, Daniel G

    2005-10-01

    The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.

  14. Clinicoelectrophysiologic and magnetoresonance and tomographic investigation of hereditary and congenital diseases of the brain

    International Nuclear Information System (INIS)

    Kamalov, I.I.; Pikuza, O.I.; Idrisova, L.G.; Uryvskij, V.I.

    1996-01-01

    The combined investigation of hereditary and congenital diseases of the brain using magnetoresonance tomography is performed. The hereditary and congenital diseases of the brain accompanied by disorders of liquoroconductive tracts with medullary substance lesion are revealed. The investigation results provide timely development of the treatment tactics and rehabilitation of sick children. Refs. 3

  15. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Kjeldsen, J

    2000-01-01

    Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

  16. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised

  17. Management of acute attacks of hereditary angioedema: potential role of icatibant.

    Science.gov (United States)

    Longhurst, Hilary J

    2010-09-07

    Icatibant (Firazyr(®)) is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema.

  18. Management of acute attacks of hereditary angioedema: potential role of icatibant

    Science.gov (United States)

    Longhurst, Hilary J

    2010-01-01

    Icatibant (Firazyr®) is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema. PMID:20859548

  19. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  20. Cellular Pathways of Hereditary Spastic Paraplegia*

    OpenAIRE

    Blackstone, Craig

    2012-01-01

    Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticul...

  1. Hereditary iron and copper deposition

    DEFF Research Database (Denmark)

    Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

    2007-01-01

    Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about......, they may be inadequate in patients diagnosed so late that extensive body deposits of metal have been developed. The main research needs in this field are to further clarify molecular mechanisms of disease progression and to develop new chelators that are more effective and less toxic than those presently...

  2. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.

    NARCIS (Netherlands)

    Swinkels, D.W.; Janssen, M.C.H.; Bergmans, J.; Marx, J.J.M.

    2006-01-01

    Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for

  3. Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

    Science.gov (United States)

    Haidas, S; Zannos-Mariolea, L; Matsaniotis, N

    1975-12-01

    The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

  4. Hereditary angioedema in women

    Directory of Open Access Journals (Sweden)

    Bouillet Laurence

    2010-07-01

    Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

  5. Comparison of Attitudes Regarding Preimplantation Genetic Diagnosis Among Patients with Hereditary Cancer Syndromes

    Science.gov (United States)

    Rich, Thereasa A.; Liu, Mei; Etzel, Carol J.; Bannon, Sarah A.; Mork, Maureen E.; Ready, Kaylene; Saraiya, Devki S.; Grubbs, Elizabeth G.; Perrier, Nancy D.; Lu, Karen H.; Arun, Banu K.; Woodard, Terri L.; Schover, Leslie R.; Litton, Jennifer K.

    2014-01-01

    Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered. PMID:24072553

  6. Could Ossification of the Achilles Tendon Have a Hereditary Component?

    Directory of Open Access Journals (Sweden)

    Chawki Cortbaoui

    2013-01-01

    Full Text Available Ossification of the Achilles tendon (OTA is an unusual clinical condition. It is characterized by the presence of an ossified mass within the fibrocartilaginous substance of the Achilles tendon. The etiology of the ossification of the Achilles tendon is unknown. Review of the literature suggests that its etiology is multifactorial. The major contributing factors are trauma and surgery with other minor causes such as systemic diseases, metabolic conditions, and infections. To our knowledge, no previous reports suggest any genetic/hereditary predisposition in OAT. We report 3 siblings who have OAT with no history of any of the aforementioned predisposing factors. Could OAT have a hereditary component as one of its etiologies?

  7. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  8. Clinical and genetic characteristics of Pseudohypoparathyroidism in the Chinese population.

    Science.gov (United States)

    Chu, Xueying; Zhu, Yan; Wang, Ou; Nie, Min; Quan, Tingting; Xue, Yu; Wang, Wenbo; Jiang, Yan; Li, Mei; Xia, Weibo; Xing, Xiaoping

    2018-02-01

    Pseudohypoparathyroidism (PHP) is caused by mutations and epimutations in the GNAS locus, and characterized by the possibility of resistance to multiple hormones and Albright's hereditary osteodystrophy. PHP can be classified into the forms 1A/C, sporadic 1B and familial 1B. To obtain an overall view of the clinical and genetic characteristics of the Chinese PHP patient population. From 2000 to 2016, 120 patients were recruited and studied using Sanger sequencing, methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) and combined bisulfite restriction analysis (COBRA). Of these patients, 104 had positive molecular alterations indicative of certain forms of PHP and were included in data analysis. Clinical and laboratory features were compared between PHP1A/C and PHP1B patients. Ten PHP1A/C, 21 familial PHP1B and 73 sporadic PHP1B patients were identified. Four novel GNAS mutations were discovered in these patients, including c.1038+1G>T, c.530+2T>C, c.880_883delCAAG and c.311_312delAAG, insT. The most common symptoms in this series were recurrent tetany (89.4%) and epilepsy (47.1%). The prevalence of weight excess increased with age for PHP1B (10%-35%) and PHP1A/C (50%-75%). Intracranial calcification had a prevalence of 94.6% and correlated with seizures (r = .227, P = .029). Cataracts occurred in 56.2% PHP patients, and there was a trend towards longer disease duration in patients with cataracts (P = .051). Statistically significant differences (P PHP1B and PHP1A/C patients, including age of onset (10 vs 7 year), short stature (21.3% vs 70%), rounded face (60.6% vs 100%), brachydactyly (25.5% vs 100%), ectopic ossification (1.1% vs 40%) and TSH resistance (44.6% vs 90%), respectively. This study is the largest single-centre series of PHP patients and summarizes the clinical and genetic features of the Chinese PHP population. While there was substantial clinical overlap between PHP1A/C and PHP1B, differences in disease progression

  9. Hereditary effects in eccentric compact binary inspirals to third post-Newtonian order

    Science.gov (United States)

    Loutrel, Nicholas; Yunes, Nicolás

    2017-02-01

    While there has been much success in understanding the orbital dynamics and gravitational wave emission of eccentric compact binaries in the post-Newtonian formalism, some problems still remain. The largest of these concerns hereditary effects: non-linear phenomena related to the scattering off of the background curved spacetime (tails) and to the generation of gravitational waves by gravitational waves (memory). Currently, these hereditary effects are only known numerically for arbitrary eccentricity through infinite sums of Bessel functions, with closed-form, analytic results only available in the small eccentricity limit. We here calculate, for the first time, closed-form, analytic expressions for all hereditary effects to third post-Newtonian order in binaries with arbitrary eccentricity. For the tails, we first asymptotically expand all Bessel functions in high eccentricity and find a superasymptotic series for each enhancement factor, accurate to better than 10-3 relative to post-Newtonian numerical calculations at all eccentricities. We further improve the small-eccentricity behavior of the superasymptotic series by generating hyperasymptotic expressions for each enhancement factor, typically accurate to better than 10-8 at all eccentricities. For the memory, we discuss its computation within the context of an osculating approximation of the binary’s orbit and the difficulties that arise. Our closed-form analytic expressions for the hereditary fluxes allow us to numerically compute orbital phases that are identical to those found using an infinite sum of Bessel functions to double numerical precision.

  10. Hereditary effects in eccentric compact binary inspirals to third post-Newtonian order

    International Nuclear Information System (INIS)

    Loutrel, Nicholas; Yunes, Nicolás

    2017-01-01

    While there has been much success in understanding the orbital dynamics and gravitational wave emission of eccentric compact binaries in the post-Newtonian formalism, some problems still remain. The largest of these concerns hereditary effects: non-linear phenomena related to the scattering off of the background curved spacetime (tails) and to the generation of gravitational waves by gravitational waves (memory). Currently, these hereditary effects are only known numerically for arbitrary eccentricity through infinite sums of Bessel functions, with closed-form, analytic results only available in the small eccentricity limit. We here calculate, for the first time, closed-form, analytic expressions for all hereditary effects to third post-Newtonian order in binaries with arbitrary eccentricity. For the tails, we first asymptotically expand all Bessel functions in high eccentricity and find a superasymptotic series for each enhancement factor, accurate to better than 10 −3 relative to post-Newtonian numerical calculations at all eccentricities. We further improve the small-eccentricity behavior of the superasymptotic series by generating hyperasymptotic expressions for each enhancement factor, typically accurate to better than 10 −8 at all eccentricities. For the memory, we discuss its computation within the context of an osculating approximation of the binary’s orbit and the difficulties that arise. Our closed-form analytic expressions for the hereditary fluxes allow us to numerically compute orbital phases that are identical to those found using an infinite sum of Bessel functions to double numerical precision. (paper)

  11. Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

    OpenAIRE

    Chu Annie TW; Bonanno George A; Ho Judy WC; Ho Samuel MY; Chan Emily MS

    2010-01-01

    Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer R...

  12. Autosomal dominant hereditary ataxia in Sri Lanka

    OpenAIRE

    Sumathipala, Dulika S; Abeysekera, Gayan S; Jayasekara, Rohan W; Tallaksen, Chantal ME; Dissanayake, Vajira HW

    2013-01-01

    Background Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. Methods ...

  13. A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

    Science.gov (United States)

    Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

    2017-01-04

    We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

  14. [Molecular genetic diagnostics and screening of hereditary hemochromatosis].

    Science.gov (United States)

    Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

    2006-06-01

    Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily

  15. Multiple Hereditary Osteochondromatosis: A Case Report

    OpenAIRE

    K???kesmen, ?i?dem; ?zen, Bu?ra; Ak?am, Mustafa

    2007-01-01

    Objectives Common carious lesions owing to vomiting are not widespread in children. In this case, we aimed to report an 11-years-old male patient with common carious lesions due to repeated vomitings, chewing and eating difficulty and retarded growth with Multiple Hereditary Osteochondromatosis (MHO). Case Report An 11-years-old boy was referred to Department of Pediatric Dentistry in Faculty of Dentistry because of eating difficulty owing to common carious lesions. It was seen that the patie...

  16. Pancreatic cancer risk in hereditary pancreatitis

    OpenAIRE

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  17. Current problems in haematology. 2: Hereditary spherocytosis.

    OpenAIRE

    Smedley, J C; Bellingham, A J

    1991-01-01

    Hereditary spherocytosis is a relatively common haematological disorder and will be encountered by all haematologists. The abundance of new information, dealing principally with molecular and genetic aspects of pathophysiology, is beginning to have implications for its investigation and management. While these advances have not yet exerted a large influence at therapeutic level, the promise of such advents as prenatal diagnosis make this an exciting field to watch.

  18. Multimodality imaging features of hereditary multiple exostoses

    OpenAIRE

    Kok, H K; Fitzgerald, L; Campbell, N; Lyburn, I D; Munk, P L; Buckley, O; Torreggiani, W C

    2013-01-01

    Hereditary multiple exostoses (HME) or diaphyseal aclasis is an inherited disorder characterised by the formation of multiple osteochondromas, which are cartilage-capped osseous outgrowths, and the development of associated osseous deformities. Individuals with HME may be asymptomatic or develop clinical symptoms, which prompt imaging studies. Different modalities ranging from plain radiographs to cross-sectional and nuclear medicine imaging studies can be helpful in the diagnosis and detecti...

  19. Hereditary Portfolio Optimization with Taxes and Fixed Plus Proportional Transaction Costs—Part II

    Directory of Open Access Journals (Sweden)

    Mou-Hsiung Chang

    2007-01-01

    Full Text Available This paper is the continuation of the paper entitled “Hereditary portfolio optimization with taxes and fixed plus proportional transaction costs I” that treats an infinite-time horizon hereditary portfolio optimization problem in a market that consists of one savings account and one stock account. Within the solvency region, the investor is allowed to consume from the savings account and can make transactions between the two assets subject to paying capital-gain taxes as well as a fixed plus proportional transaction cost. The investor is to seek an optimal consumption-trading strategy in order to maximize the expected utility from the total discounted consumption. The portfolio optimization problem is formulated as an infinite dimensional stochastic classical impulse control problem due to the hereditary nature of the stock price dynamics and inventories. This paper contains the verification theorem for the optimal strategy. It also proves that the value function is a viscosity solution of the QVHJBI.

  20. Surgical treatment of hereditary lens subluxations.

    Science.gov (United States)

    Ozdek, Sengul; Sari, Ayca; Bilgihan, Kamil; Akata, Fikret; Hasanreisoglu, Berati

    2002-01-01

    To evaluate the effectiveness and results of pars plana vitreolensectomy approach with transscleral fixation of intraocular lens in hereditary lens subluxations. Fifteen eyes of 9 consecutive patients with a mean age of 12.8+/-6.2 years (6-26 years) with hereditary lens subluxation were operated on and the results were evaluated in a prospective study. Surgery was considered if best spectacle corrected visual acuity (BSCVA) was less than 20/70. All eyes underwent a 2-port pars plana vitreolensectomy and transscleral fixation of an intraocular lens (IOL). The mean follow-up period was 12.6+/-7.5 months (6-22 months). There was no major intraoperative complication. Preoperatively, 8 eyes (53.3%) had a BSCVA of counting fingers (CF) and 7 eyes (46.6%) had a BSCVA of 20/200 to 20/70. Postoperatively, 14 eyes (93.3%) had a BSCVA of 20/50 or better. None of the patients had IOL decentration or intraocular pressure (IOP) increase during the follow-up period. There was a macular hole formation in 1 eye postoperatively. The early results of pars plana vitreolensectomy with IOL implantation using scleral fixation technique had shown that it not only promises a rapid visual rehabilitation but it is also a relatively safe method. More serious complications, however, may occur in the long term.

  1. Motor activation in SPG4-linked hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Scheuer, KH; Nielsen, JE; Krabbe, Katja

    2006-01-01

    OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS: T...

  2. An ABC of the Warning Signs of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Grumach, Anete Sevciovic; Ferraroni, Natasha; Olivares, Maria Margarita

    2017-01-01

    Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased...

  3. Iron in hereditary retinal degeneration: PIXE microanalysis Preliminary results

    International Nuclear Information System (INIS)

    Sergeant, C.; Gouget, B.; Llabador, Y.; Simonoff, M.; Yefimova, M.; Courtois, Y.; Jeanny, J.C.

    1999-01-01

    Several types of hereditary retinal degeneration with progressive alteration of photoreceptors exist in men and animals. Recent immunohistochemical results have shown strong degradation of transferrin, the protein responsible for iron transport, in retinas of rats with hereditary retinal degeneration. Freeze-dried thin sections of rat retinas from different stages of the disease, and respective coeval control sections, have been analyzed using nuclear microprobe. In this first part of the study, the rat retinas at post-natal stages of 35 and 45 days have been analyzed. The sample preparation and the post-irradiation staining to determine precisely the retinal layers involved are described. Preliminary results of element distributions (K, Ca, Fe) in the rat retina layers are discussed. A very high content of calcium in the choriocapillaris of dystrophic rat retinas was observed. Preliminary results on iron distribution in the rat retina layers are presented

  4. Ethical, social and counselling issues in hereditary cancer susceptibility.

    Science.gov (United States)

    Garber, J E; Patenaude, A F

    1995-01-01

    Genetic testing for hereditary susceptibility to disease is new. Much has been learned from experience with Huntington's disease and other non-malignant conditions. There are some differences in the case of predisposition testing for cancer: there is often the perception that cancer is preventable and sometimes curable, in contrast to other hereditary conditions. Testing raises many issues new to the medical community and to the public as well. There is great concern that the explosive technology be used responsibly, so that the potential benefits of genetic knowledge are not eclipsed by the risks to autonomy, privacy and justice. Practical concerns about insurability and discrimination may inhibit some at risk individuals from taking advantage of this powerful technology. There has been considerable effort already in the UK, Europe and the USA at the research and social levels to create protection for individuals found to carry genetic susceptibility to disease.

  5. Hereditary hemochromatosis and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjaerg-Hansen, Anne; Grande, Peer

    2005-01-01

    BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS: We performed a prospective study of 9178 individuals from the Danish...

  6. Suspected Perinatal Depression Revealed to be Hereditary Diffuse Leukoencephalopathy with Spheroids.

    Science.gov (United States)

    Blume, Josefine; Weissert, Robert

    2017-01-01

    Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

  7. Suspected Perinatal Depression Revealed to be Hereditary Diffuse Leukoencephalopathy with Spheroids

    Directory of Open Access Journals (Sweden)

    Josefine Blume

    2017-01-01

    Full Text Available Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

  8. Whole-exome sequencing for diagnosis of hereditary ichthyosis.

    Science.gov (United States)

    Sitek, J C; Kulseth, M A; Rypdal, K B; Skodje, T; Sheng, Y; Retterstøl, L

    2018-02-14

    Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively. Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). Whole-exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first-tier genetic test in these patients. © 2018 European Academy of Dermatology and Venereology.

  9. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

  10. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  11. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, R. J.; Tijmes, N. T.; Cobben, J. M.; Bolhuis, P. A.; van Nesselrooij, B. P.; Houtman, W. A.; de Kok-Nazaruk, M. M.; Bleeker-Wagemakers, E. M.

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  12. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

    Directory of Open Access Journals (Sweden)

    Pavri Roshan

    1977-01-01

    Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

  13. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era

    Directory of Open Access Journals (Sweden)

    Jamie eMcDonald

    2015-01-01

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curaçao diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS HHT panel is proposed.

  14. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  15. Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

    Science.gov (United States)

    McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

    2013-12-17

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

  16. Hereditary arrhythmias and cardiomyopathies: decision-making about genetic testing.

    Science.gov (United States)

    Louis, Clauden; Calamaro, Emily; Vinocur, Jeffrey M

    2018-01-01

    The modern field of clinical genetics has advanced beyond the traditional teachings familiar to most practicing cardiologists. Increased understanding of the roles of genetic testing may improve uptake and appropriateness of use. Clinical genetics has become integral to the management of patients with hereditary arrhythmia and cardiomyopathy diagnoses. Depending on the condition, genetic testing may be useful for diagnosis, prognosis, treatment, family screening, and reproductive planning. However, genetic testing is a powerful tool with potential for underuse, overuse, and misuse. In the absence of a substantial body of literature on how these guidelines are applied in clinical practice, we use a case-based approach to highlight key lessons and pitfalls. Importantly, in many scenarios genetic testing has become the standard of care supported by numerous class I recommendations; genetic counselors can improve accessibility to and appropriate use and application of testing. Optimal management of hereditary arrhythmias and cardiomyopathies incorporates genetic testing, applied as per consensus guidelines, with involvement of a multidisciplinary team.

  17. Recommendations regarding splenectomy in hereditary hemolytic anemias

    Science.gov (United States)

    Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

    2017-01-01

    Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

  18. Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment

    Directory of Open Access Journals (Sweden)

    Valentina S. Vysotskaia

    2017-02-01

    Full Text Available The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs, short insertions and deletions (indels, and copy number variants (CNVs in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA. We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.

  19. Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

    Science.gov (United States)

    Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

    2018-01-01

    Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

  20. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  1. Severe fatigue and reduced quality of life in children with hereditary motor and sensory neuropathy 1A

    NARCIS (Netherlands)

    Jagersma, Elbrich; Jeukens-Visser, Martine; van Paassen, Barbara W.; Meester-Delver, Anke; Nollet, Frans

    2013-01-01

    Severe fatigue and low quality of life are reported by a majority of adult patients with hereditary motor and sensory neuropathy 1A. In children with hereditary motor and sensory neuropathy 1A, the prevalence and impact of fatigue have not been studied yet. In this questionnaire survey, 55 Dutch

  2. Hereditary chronic pancreatitis in a patient with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Varalakshmi Muthukrishnan

    2018-01-01

    Full Text Available In this case report, we present a young patient with type 1 diabetes who had hereditary chronic pancreatitis. We evaluated him for the cause of pancreatitis, but it was inconclusive and finally the genetic testing was done for him, which revealed heterozygous missense mutation in exon 3 of the PRSS1 gene (protease serine 1 gene on chromosome 7. Hence, we were able to make the diagnosis of hereditary chronic pancreatitis. Chronic pancreatitis secondary to any cause can lead to permanent diabetes, which is typically difficult to control. However, in this case, the episodes of recurrent pancreatitis were present after the onset of type 1 diabetes as compared to the usual presentation of diabetes after the advancement of chronic pancreatitis.

  3. Recurrent IVF failure and hereditary thrombophilia.

    Science.gov (United States)

    Safdarian, Leila; Najmi, Zahra; Aleyasin, Ashraf; Aghahosseini, Marzieh; Rashidi, Mandana; Asadollah, Sara

    2014-07-01

    The largest percentage of failed invitro fertilization (IVF (cycles, are due to lack of implantation. As hereditary thrombophilia can cause in placentation failure, it may have a role in recurrent IVF failure. Aim of this case-control study was to determine whether hereditary thrombophilia is more prevalent in women with recurrent IVF failures. Case group comprised 96 infertile women, with a history of recurrent IVF failure. Control group was comprised of 95 healthy women with proven fertility who had conceived spontaneously. All participants were assessed for the presence of inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between groups. Having at least one thrombophilia known as a risk factor for recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation (95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF failure. However, we could not find significant difference in other inherited thrombophilia's. Inherited thrombophilia is more prevalent in women with recurrent IVF failure compared with healthy women. Having at least one thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation were risk factors for recurrent IVF failure.

  4. Mania associated with complicated hereditary spastic paraparesis

    OpenAIRE

    Raghavendra B Nayak; Govind S Bhogale; Nanasaheb M Patil; Aditya A Pandurangi

    2011-01-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints ...

  5. Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

    Science.gov (United States)

    Panas, Marios; Kalfakis, Nikolaos; Karadima, Georgia; Davaki, Panagiota; Vassilopoulos, Demetris

    2002-11-01

    Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.

  6. Hereditary spastic paraplegia.

    Science.gov (United States)

    Blackstone, Craig

    2018-01-01

    The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.

    Science.gov (United States)

    Newton, Timothy; Allison, Rachel; Edgar, James R; Lumb, Jennifer H; Rodger, Catherine E; Manna, Paul T; Rizo, Tania; Kohl, Zacharias; Nygren, Anders O H; Arning, Larissa; Schüle, Rebecca; Depienne, Christel; Goldberg, Lisa; Frahm, Christiane; Stevanin, Giovanni; Durr, Alexandra; Schöls, Ludger; Winner, Beate; Beetz, Christian; Reid, Evan

    2018-05-01

    Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.

  8. Brain abscesses and hereditary hemorrhagic telangiectasia

    International Nuclear Information System (INIS)

    Vives, Daniel A.; Bauni, Carlos E.; Mendoza, Monica E.

    2003-01-01

    Rendu-Osler-Weber disease or Hereditary Hemorrhagic Telangiectasia (HHT) is a generalized familial angiodysplastic disorder. The neurological manifestations of this entity are due to Central Nervous System vascular lesions or to complications of other visceral lesions such as pulmonary arteriovenous fistulae. This report describes two patients (males, 40 and 61 years old), with brain abscesses associated with HHT. The CT, MRI and Angiographic findings as well as the therapeutic approach are analyzed. Patients with brain abscess of unknown origin must be evaluated for the presence of lung vascular malformation in association with HHT. (author)

  9. Bone scintigraphy in hereditary multiple exostoses

    International Nuclear Information System (INIS)

    Epstein, D.A.; Levin, E.J.

    1978-01-01

    Two adult patients with multiple hereditary exostoses, a skeletal disorder with recognized malignant potential, each demonstrated increased /sup 99m/Tc diphosphonate uptake in an exostosis in which renewed growth had begun. None of the other multiple exostoses in either patient showed abnormal uptake. Histologic study of the lesions demonstrated chondrosarcoma in one case and benign osteochondroma in the second. Although bone scintigraphy nonspecifically identifies bone growth rather than malignant degeneration, it is more useful than radiographic bone survey in the periodic surveillance of adult patients with this disorder

  10. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    NARCIS (Netherlands)

    Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

    2011-01-01

    Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

  11. The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.

    NARCIS (Netherlands)

    Verzijl, H.T.F.M.; Zwaag, B. van der; Lammens, M.M.Y.; Donkelaar, H.J. ten; Padberg, G.W.A.M.

    2005-01-01

    OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial

  12. Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

    2011-01-01

    In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic...

  13. Android Mobile Informatics Application for some Hereditary Diseases and Disorders (AMAHD: A complementary framework for medical practitioners and patients

    Directory of Open Access Journals (Sweden)

    Olugbenga Oluwagbemi

    Full Text Available Hereditary diseases and disorders constitute a public health problem. Many people in rural communities of developing countries of the world are particularly ignorant about the cause, modes of transmissions and the treatment plans for such diseases. In some cases, some people lack essential knowledge between common and rare hereditary diseases.It is therefore appropriate and essential to develop a mobile application that will act as an educative resource and a good knowledge base for common and rare hereditary diseases.The aim of this research is to develop AMAHD (Android Mobile Informatics Application for some Hereditary Diseases and Disorders.The objectives of this research are to create an android mobile application that will act as a reference point and provide useful information about various hereditary diseases to medical personnel and professionals; provide additional educational resource to biological and bioinformatics researchers in different higher institutions; and provide a pedagogical, diagnostic and complementary foundational learning tool for African research students in biosciences, bioinformatics, and all other categories of students that currently engage in multidisciplinary research in the aspect of hereditary diseases.Essential data was sourced from relevant literature. We developed AMAHD through an integration of programming languages in Java and XML (Extended Markup Language. SQLite was used to implement the database. We developed a Logical Disjunction Rule-based Algorithm (LDRA for the AMAHD’s diagnosis module.A comparative analysis between existing commercial hereditary mobile applications and AMAHD was conducted and the results presented. A world-wide online survey (spanning Africa, Asia, Europe, America and Australia was conducted to sample the opinion of individuals across the globe on the classification of hereditary diseases as either rare or common, within their respective regions. In addition, an evaluation of

  14. Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a young female patient with hereditary hemochromatosis.

    Science.gov (United States)

    Höblinger, A; Erdmann, C; Strassburg, C P; Sauerbruch, T; Lammert, F

    2009-04-16

    Here we report a 33-years-old woman with hereditary spherocytosis and hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The coinheritance of both conditions led to severe iron overload and liver cirrhosis at young age. The patient was treated by repeated phlebotomy, and reversibility of cirrhosis was documented by transient elastography. This report discusses the pathophysiology of iron accumulation in patients with hemolytic anemia combined with HFE C282Y homozygosity. The case indicates that patients with hematological disorders characterized by increased erythropoetic activity should be screened for HFE mutations.

  15. [Hereditary motor and sensory Lom-neuropathy--first Hungarian case report].

    Science.gov (United States)

    Szabó, Antal; Siska, Eva; Molnár, Mária Judit

    2007-01-20

    Hereditary motor and sensory neuropathy-Lom is an autosomal recessive disorder of the peripheral nervous system, which occurs only in the european Roma population. The symptoms start in the first decade with slowly progressive gait disturbance, weakness and wasting of distal upper extremity muscles, joint deformities and hearing loss develop later in the second and third decades. This disorder is caused by a homozygous missense mutation of the NDRG1 gene, located in the 8q24 region. The Schwann cell dysfunction is most probably caused by altered lipid metabolism as a consequence of the NDRG1 mutation. Molecular genetic testing can be a first diagnostic step among roma individuals showing a Lom neuropathy phenotype, making evaluation of such patients and also genetic counselling faster and easier. Screening for hereditary neuromuscular disorders in this genetically isolated community may become an important public health issue in the near future.

  16. Orthodontic treatment for a patient with hereditary angiodema: a case report.

    Science.gov (United States)

    Waldon, Kate; Barber, Sophy Kathleen; Spencer, Richard James

    2015-05-01

    Hereditary angiodema (HAE), also known as C1 esterase inhibitor deficiency, causes sufferers to experience episodic subcutaneous and submucosal oedema. These episodes can be triggered by dental treatment and manifest as life-threatening oedematous swelling in the head and neck region. This case report reviews an adolescent with hereditary angiodema whose malocclusion required orthodontic intervention. Due to her complex and unpredictable reaction to dental treatment, various options were explored before determining the appropriate care pathway for this patient. Trial placement of a sectional fixed appliance tested the tissue reaction prior to comprehensive treatment including extractions and fixed orthodontic appliances. This report demonstrates successful interdisciplinary management facilitating orthodontic care in a patient with HAE. © 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

    Science.gov (United States)

    Kravochuck, Sara E; Church, James M

    2017-12-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

  18. Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

    OpenAIRE

    Wang, Xu-Lin; Yuan, Ying; Zhang, Su-Zhan; Cai, Shan-Rong; Huang, Yan-Qin; Jiang, Qiang; Zheng, Shu

    2006-01-01

    AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.

  19. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    2012-01-01

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  20. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  1. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

    Science.gov (United States)

    Cicardi, Marco; Banerji, Aleena; Bracho, Francisco; Malbrán, Alejandro; Rosenkranz, Bernd; Riedl, Marc; Bork, Konrad; Lumry, William; Aberer, Werner; Bier, Henning; Bas, Murat; Greve, Jens; Hoffmann, Thomas K; Farkas, Henriette; Reshef, Avner; Ritchie, Bruce; Yang, William; Grabbe, Jürgen; Kivity, Shmuel; Kreuz, Wolfhart; Levy, Robyn J; Luger, Thomas; Obtulowicz, Krystyna; Schmid-Grendelmeier, Peter; Bull, Christian; Sitkauskiene, Brigita; Smith, William B; Toubi, Elias; Werner, Sonja; Anné, Suresh; Björkander, Janne; Bouillet, Laurence; Cillari, Enrico; Hurewitz, David; Jacobson, Kraig W; Katelaris, Constance H; Maurer, Marcus; Merk, Hans; Bernstein, Jonathan A; Feighery, Conleth; Floccard, Bernard; Gleich, Gerald; Hébert, Jacques; Kaatz, Martin; Keith, Paul; Kirkpatrick, Charles H; Langton, David; Martin, Ludovic; Pichler, Christiane; Resnick, David; Wombolt, Duane; Fernández Romero, Diego S; Zanichelli, Andrea; Arcoleo, Francesco; Knolle, Jochen; Kravec, Irina; Dong, Liying; Zimmermann, Jens; Rosen, Kimberly; Fan, Wing-Tze

    2010-08-05

    Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

  2. Prophylactic Therapy for Hereditary Angioedema.

    Science.gov (United States)

    Longhurst, Hilary; Zinser, Emily

    2017-08-01

    Long-term prophylaxis is needed in many patients with hereditary angioedema and poses many challenges. Attenuated androgens are effective in many but are limited by side effect profiles. There is less evidence for efficacy of tranexamic acid and progestagens; however, the small side effect profile makes tranexamic acid an option for prophylaxis in children and progestagens an option for women. C1 inhibitor is beneficial, but at present requires intravenous delivery and may need dose titration for maximum efficacy. Short-term prophylaxis should be considered for all procedures. New therapies are promising in overcoming many problems encountered with current options for long-term prophylaxis. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Treatment of Hereditary Hemorrhagic Telangiectasia-Related Epistaxis.

    Science.gov (United States)

    Sautter, Nathan B; Smith, Timothy L

    2016-06-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an incidence of 1:5000. Recurrent, spontaneous epistaxis is the most common presenting symptom. Severity of epistaxis varies widely, from mild, self-limited nosebleeds to severe, life-threatening nasal hemorrhage. Treatment of HHT-related epistaxis presents a challenge to the otolaryngologist due to the recurrent, persistent nature of epistaxis often requiring multiple treatments. Treatment modalities range from conservative topical therapies to more aggressive surgical treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Genes for hereditary sensory and autonomic neuropathies : a genotype-phenotype correlation

    NARCIS (Netherlands)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven

  5. Generation of patient-specific induced pluripotent stem cells from Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Huai-En Lu

    2018-04-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease caused by homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. In this report, we generated an induced pluripotent stem cell (iPSCs line, TVGH-iPSC-010-09, from the peripheral blood mononuclear cells of a female patient with Leber's hereditary optic neuropathy (LHON by using the Sendai-virus delivery system. The resulting iPSCs retained the disease-causing mitochondrial DNA mutation, expressed pluripotent markers and could differentiate into the three germ layers. We believe LHON patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.

  6. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    DEFF Research Database (Denmark)

    Bygum, Anette

    2014-01-01

    stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...

  7. A role for MLH3 in hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    Wu, Y; Berends, MJW; Sijmons, RH; Mensink, RGJ; Verlind, E; Kooi, KA; van der Sluis, T; Kempinga, C; van der Zee, AGJ; Hollema, H; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW

    2001-01-01

    We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations,

  8. Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

    Science.gov (United States)

    Rudanko, S.-L.

    1995-01-01

    This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

  9. The establishment and utility of Sweha-Reg: a Swedish population-based registry to understand hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Werner Sonja

    2007-11-01

    Full Text Available Abstract Background The importance of acquiring comprehensive epidemiological and clinical data on hereditary angioedema has increasingly caught the attention of physicians and scientists around the world. The development of networks and creation of comprehensive policies to improve care of people suffering from rare diseases, such as hereditary angioedema, is a stated top priority of the European Union. Hereditary angioedema is a rare disease, that it may be life-threatening. Although the exact prevalence is unknown, current estimates suggest that it is 1/10,000–1/150,000 individuals. The low prevalence requires combined efforts to gain accurate epidemiological data on the disease and so give us tools to reduce morbidity and mortality, and improve quality of life of sufferers. Methods Sweha-Reg is a population-based registry of hereditary angioedema in Sweden with the objectives of providing epidemiological data, and so creates a framework for the study of this disease. The registry contains individual-based data on diagnoses, treatments and outcomes. Conclusion The present manuscript seeks to raise awareness of the existence of Sweha-Reg to stimulate the international collaboration of registries. A synthesis of data from similar registries across several countries is required to approach an inclusive course understanding of HAE.

  10. Visão atual da hemocromatose hereditária Current approach to hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    2010-01-01

    Full Text Available A hemocromatose hereditária (HH está relacionada a diversos distúrbios do metabolismo do ferro que ocasionam sua sobrecarga tecidual. A HH clássica está associada às mutações do gene HFE (homozigose para C282Y ou duplo heterozigose para C282Y/H63D, sendo encontrada quase exclusivamente em descendentes do norte Europeu. A hemocromatose hereditária, quando não relacionada ao gene HFE, é causada por mutações de outros genes, recentemente identificados, envolvidos no metabolismo do ferro. Hepcedina é o hormônio regulador do ferro que inibe a ferroportina, proteína exportadora de ferro dos enterócitos e dos macrófagos; um defeito na expressão do gene da hepcedina ou na sua função costuma ser a causa da maioria dos tipos de hemocromatose hereditária. Os alvos acometidos pela HH são órgãos e tecidos - fígado, coração, pâncreas, articulações e pele -, sendo a cirrose e o diabetes melito os sinais tardios da doença em pacientes com expressivo aumento da concentração hepática de ferro. Pacientes com diagnóstico estabelecido de hemocromatose hereditária e sobrecarga de ferro devem ser tratados com flebotomia para a obtenção de depleção do ferro do organismo; em seguida, com flebotomia de manutenção. As causas mais frequentes de morte por hemocromatose hereditária são câncer hepático, cirrose, miocardiopatia e diabete; entretanto, pacientes submetidos à depleção do ferro de maneira satisfatória e antes do desenvolvimento da cirrose ou da diabete podem ter sobrevida normal.Hereditary hemochromatosis refers to several inherited disorders of the iron metabolism that lead to tissue iron overload. Classical hereditary hemochromatosis is associated with mutations of the HFE gene (C282Y homozygotes or C282Y/H63D compound heterozygotes and is almost exclusively found in populations of northern European descent. Non-HFE-associated hereditary hemochromatosis is caused by mutations in other recently identified genes

  11. Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

    Science.gov (United States)

    Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

    2017-11-15

    Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

  12. Atypical hereditary sensory and autonomic neuropathy type IV with neither mental retardation nor pain insensitivity.

    Science.gov (United States)

    Jung, Chae Lim; Ki, Chang-Seok; Kim, Byoung Joon; Lee, Jong-Hyuck; Sung, Ki-Sun; Kim, Jong-Won; Park, Youn-Soo

    2013-12-01

    Hereditary sensory and autonomic neuropathy type IV is an autosomal recessive disorder characterized by severe mental retardation and self-mutilation-related complications. Recently, we investigated a 16-year-old Korean boy with normal intelligence. He had preserved pain sensation but was suspected of having hereditary sensory and autonomic neuropathy type IV because of the recurrent bone fractures and painless joint destruction in the absence of any predisposing medical conditions. Genetic analysis of the NTRK1 gene revealed compound heterozygous mutations including c.851-33T>A and c.2303C>T (p.Pro768Leu) in the NTRK1 gene. The p.Pro768Leu mutation has been identified in 2 Japanese patients with a mild phenotype. Therefore, although it is rare, hereditary sensory and autonomic neuropathy type IV should be considered in patients with recurrent bone fractures and painless joint destruction who do not have any predisposing conditions even when they do not have typical clinical features such as mental retardation or pain insensitivity.

  13. Utilization of the higher plants in a study on hereditary effect of low-dose irradiation

    International Nuclear Information System (INIS)

    Yamashita, Jun

    1976-01-01

    Some problems in a study of hereditary effect of low-dose irradiation, which used the higher plants (tradescantia, peas, etc.) as materials, were mentioned. Conditions to be used as materials were mentioned as follows: 1) the materials must have high radio-sensitivity, 2) the natural mutation of the materials must be low, 3) hereditary uniformity and stability of genes in the materials were important, and 4) in case of considering the materials as environmental radiation monitors, the observation period must be long and the duration from exposure to detection of mutation must be short. Tradescantia has most of these conditions, but the greatest fault is that the object of its observation is mutation of somatic cells, and hereditary study is impossible. Therefore, it is necessary to find out other materials in order to solve the problem whether there is a difference in relative frequency of chromosomal abnormalities, which occurrs in germinal cells and is transmitted to posterity, between low and high doses or not. (Serizawa, K.)

  14. Clinical and electromyographic criteria for the diagnosis of hereditary myotonic syndromes

    Directory of Open Access Journals (Sweden)

    V. P. Fedotov

    2012-01-01

    Full Text Available Hereditary myotonic syndromes (HMS are a group of genetically heterogeneous diseases of the chlorine and sodium ion channels (channelopathies with evident clinical polymorphism and high prevalence in the population. The differential diagnosis of early‑stage NMS poses a challenge to clinicians to this day. The investigation has attempted to elaborate informative differentiating criteria on the basis of a clinical and electromyographic study of 2 groups of patients with hereditary Thomsen or Becker myotonia (n = 45 and myotonic dystrophy type 1 (n = 39 verified by DNA analysis of the CLCN1 and DMPK genes. Along with the clinical symptoms, there may be the value of M‑response amplitude decrement in rhythmic stimulation of the n. ulnaris and the duration of myotonic discharges at pin electromyography of the m. tibialis anterior.

  15. Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough.

    Science.gov (United States)

    Miura, Shiroh; Shibata, Hiroki; Kida, Hiroshi; Noda, Kazuhito; Tomiyasu, Katsuro; Yamamoto, Ken; Iwaki, Akiko; Ayabe, Mitsuyoshi; Aizawa, Hisamichi; Taniwaki, Takayuki; Fukumaki, Yasuyuki

    2008-10-15

    We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of hereditary motor and sensory neuropathy with autosomal dominant inheritance.

  16. Evaluation of an online family history tool for identifying hereditary and familial colorectal cancer.

    Science.gov (United States)

    Kallenberg, F G J; Aalfs, C M; The, F O; Wientjes, C A; Depla, A C; Mundt, M W; Bossuyt, P M M; Dekker, E

    2017-09-21

    Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.

  17. Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

    Science.gov (United States)

    Hasumi, Hisashi; Yao, Masahiro

    2018-03-01

    Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

    Science.gov (United States)

    Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

    2010-06-01

    Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

  19. Hereditary melanoma and predictive genetic testing: why not?

    Science.gov (United States)

    Riedijk, S R; de Snoo, F A; van Dijk, S; Bergman, W; van Haeringen, A; Silberg, S; van Elderen, T M T; Tibben, A

    2005-09-01

    Since p16-Leiden presymptomatic testing for hereditary melanoma has become available in the Netherlands, the benefits and risks of offering such testing are evaluated. The current paper investigated why the non-participants were reluctant to participate in genetic testing. Sixty six eligible individuals, who were knowledgeable about the test but had not participated in genetic testing by January 2003, completed a self-report questionnaire assessing motivation, anxiety, family dynamics, risk knowledge and causal attributions. Non-participants reported anxiety levels below clinical significance. A principal components analysis on reasons for non-participation distinguished two underlying motives: emotional and rational motivation. Rational motivation for non-participation was associated with more accurate risk knowledge, the inclination to preselect mutation carriers within the family and lower scores on anxiety. Emotional motivation for non-participation was associated with disease misperceptions, hesitation to communicate unfavourable test results within the family and higher scores on anxiety. Rational and emotional motivation for non-participation in the genetic test for hereditary melanoma was found. Emotionally motivated individuals may be reluctant to disseminate genetic risk information. Rationally motivated individuals were better informed than emotionally motivated individuals. It is suggested that a leaflet is added to the invitation letter to enhance informed decision-making about genetic testing.

  20. Prevalence of hereditary nonpolyposis colorectal cancer in patients with colorectal cancer in Iran: a systematic review

    Directory of Open Access Journals (Sweden)

    Abbas Esmaeilzadeh

    2016-07-01

    Full Text Available Introduction: Colorectal cancer (CRC is the third leading cause of cancer deaths in the world, and hereditary factors and family history are responsible for the incidence and development of the disease in 20 to 30% of cases. Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC, is the most common hereditary form of CRC that is inherited in an autosomal dominant manner. This study consisted of a systematic literature review of research articles that described the prevalence of HNPCC in Iranian patients with CRC. Methods: A systematic literature search was conducted in the PubMed, Scopus, IranMedex, and Google Scholar databases to identify relevant articles that describe HNPCC or Lynch syndrome in patients with CRC in Iran. For this purpose, a keyword search of the following terms was employed: (((Hereditary nonpolyposis colorectal cancer OR HNPCC OR Lynch syndrome AND (colorectal cancer OR familial colorectal cancer OR colon cancer OR rectal cancer OR bowel cancer AND IRAN. All eligible documents were collected, and the desired data were qualitatively analyzed.Result: Of the 67 articles that were found via the initial database search, only 12 were deemed to be of relevance to the current study. These articles included a total population of 3237 and this sample was selected and qualitatively analyzed. The findings of the review revealed that the frequency of mutation in MLH1, MSH2, PMS2, and MSH6 genes varied between 23.1% and 62.5% among the studied families. This indicated that HNPCC is linked with up to 5.5% of the total cases of colorectal cancers in Iran.Conclusion: The results of this study revealed that the hereditary form of HNPCC or Lynch syndrome is significantly high among patients with CRC in Iran

  1. Genetics of Hereditary Ataxia in Scottish Terriers.

    Science.gov (United States)

    Urkasemsin, G; Nielsen, D M; Singleton, A; Arepalli, S; Hernandez, D; Agler, C; Olby, N J

    2017-07-01

    Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction. To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers. One hundred and fifty-three Scottish Terriers were recruited through the Scottish Terrier Club of America. Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome-wide mapping was performed using both linkage- and association-based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively. Linkage and genome-wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information. This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  2. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

    Directory of Open Access Journals (Sweden)

    Asril Zahari

    2011-09-01

    Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC

  3. Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM "El Álamo III" retrospective study.

    Science.gov (United States)

    Márquez-Rodas, Iván; Pollán, Marina; Escudero, María José; Ruiz, Amparo; Martín, Miguel; Santaballa, Ana; Martínez Del Prado, Purificación; Batista, Norberto; Andrés, Raquel; Antón, Antonio; Llombart, Antonio; Fernandez Aramburu, Antonio; Adrover, Encarnación; González, Sonia; Seguí, Miguel Angel; Calvo, Lourdes; Lizón, José; Rodríguez Lescure, Álvaro; Ramón Y Cajal, Teresa; Llort, Gemma; Jara, Carlos; Carrasco, Eva; López-Tarruella, Sara

    2017-01-01

    To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Álamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. 7,641 patients were evaluable. Of them, 2,252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors.

  4. The influence of coping styles and perceived control on emotional distress in persons at risk for a hereditary heart disease

    NARCIS (Netherlands)

    Hoedemaekers, Ehy; Jaspers, Jan P. C.; Van Tintelen, J. Peter

    2007-01-01

    This prospective study investigates the influence of two coping styles (monitoring and blunting) and perceived control (health loci-is of control and mastery) on emotional distress in persons at risk of a hereditary cardiac disease. Emotional distress in people at risk for a hereditary cardiac

  5. The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

    Directory of Open Access Journals (Sweden)

    Narod Steven

    2004-02-01

    Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.

  6. Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

    Science.gov (United States)

    Martins da Silva, Ana; Cavaco, Sara; Fernandes, Joana; Samões, Raquel; Alves, Cristina; Cardoso, Márcio; Kelly, Jeffery W; Monteiro, Cecília; Coelho, Teresa

    2018-02-01

    Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

  7. HSJ1-related hereditary neuropathies: novel mutations and extended clinical spectrum.

    Science.gov (United States)

    Gess, Burkhard; Auer-Grumbach, Michaela; Schirmacher, Anja; Strom, Tim; Zitzelsberger, Manuela; Rudnik-Schöneborn, Sabine; Röhr, Dominik; Halfter, Hartmut; Young, Peter; Senderek, Jan

    2014-11-04

    To determine the nature and frequency of HSJ1 mutations in patients with hereditary motor and hereditary motor and sensory neuropathies. Patients were screened for mutations by genome-wide or targeted linkage and homozygosity studies, whole-exome sequencing, and Sanger sequencing. RNA and protein studies of skin fibroblasts were used for functional characterization. We describe 2 additional mutations in the HSJ1 gene in a cohort of 90 patients with autosomal recessive distal hereditary motor neuropathy (dHMN) and Charcot-Marie-Tooth disease type 2 (CMT2). One family with a dHMN phenotype showed the homozygous splice-site mutation c.229+1G>A, which leads to retention of intron 4 in the HSJ1 messenger RNA with a premature stop codon and loss of protein expression. Another family, presenting with a CMT2 phenotype, carried the homozygous missense mutation c.14A>G (p.Tyr5Cys). This mutation was classified as likely disease-related by several automatic algorithms for prediction of possible impact of an amino acid substitution on the structure and function of proteins. Both mutations cosegregated with autosomal recessive inheritance of the disease and were absent from the general population. Taken together, in our cohort of 90 probands, we confirm that HSJ1 mutations are a rare but detectable cause of autosomal recessive dHMN and CMT2. We provide clinical and functional information on an HSJ1 splice-site mutation and report the detailed phenotype of 2 patients with CMT2, broadening the phenotypic spectrum of HSJ1-related neuropathies. © 2014 American Academy of Neurology.

  8. Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

    Science.gov (United States)

    ... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...

  9. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations

    DEFF Research Database (Denmark)

    Ferré, Marc; Bonneau, Dominique; Milea, Dan

    2009-01-01

    We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten...... and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease....... novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1...

  10. ACOUSTIC WAVES EMISSION IN THE TWO-COMPONENT HEREDITARY-ELASTIC MEDIUM

    Directory of Open Access Journals (Sweden)

    V. S. Polenov

    2014-01-01

    Full Text Available Summary. On the dynamics of two-component media a number of papers, which address the elastic waves in a homogeneous, unbounded fluid-saturated porous medium. In other studies address issues of dissipative processes in harmonic deformation hereditary elastic medium. In the article the dissipative processes of the viscoelastic porous medium, which hereditary properties are described by the core relaxation fractional exponential function U.N. Rabotnova integro-differential Boltzmann-Volterr ratio, harmonic deformation by the straining saturated incompressible liquid are investigated. Speed of wave propagation, absorption coefficient, mechanical loss tangent, logarithmic decrement, depending on fractional parameter γ, determining formulas received. The frequency logarithm and temperature graph dependences with the goal fractional parameter are constructed. Shows the dependences velocity and attenuation coefficient of the tangent of the phase angle of the logarithm of the temperature, and the dependence of the attenuation coefficient of the logarithm of the frequency. Dependencies the speed and the tangent of the phase angle of the frequency identical function of the logarithm of temperature.

  11. De-novo mutation in hereditary motor and sensory neuropathy type I

    NARCIS (Netherlands)

    Hoogendijk, J. E.; Hensels, G. W.; Gabreëls-Festen, A. A.; Gabreëls, F. J.; Janssen, E. A.; de Jonghe, P.; Martin, J. J.; van Broeckhoven, C.; Valentijn, L. J.; Baas, F.

    1992-01-01

    Isolated cases of hereditary motor and sensory neuropathy type I (HMSN I, Charcot-Marie-Tooth disease type 1) have been thought to be most frequently autosomal recessive. We have found that a recently discovered duplication in chromosome 17, responsible for most cases of autosomal dominant HMSN I,

  12. Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

    Science.gov (United States)

    Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

    2009-01-01

    Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant ("SPTLC1"…

  13. Chaperonopathies: spotlight on hereditary motor neuropathies

    Directory of Open Access Journals (Sweden)

    Vincenzo Lupo

    2016-12-01

    Full Text Available Distal hereditary motor neuropathies (dHMN comprise a group of rare hereditary neuromuscular disorders characterized by a peroneal muscular atrophy without sensory symptoms. To date twenty-three genes for dHMN have been reported and four of them encode for chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family, and HSPB1, HSPB3 and HSPB8, which encode three members of the family of small heat shock proteins. Except for HSPB1, with around thirty different mutations, the remaining three genes comprise a much low number of cases. Thus, only one case has been described caused by an HSPB3 mutation, whereas few DNAJB2 and HSPB8 cases are known, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the hot spot K141 residue of the HSPB8 chaperone. This low number of cases makes it difficult to understand the pathomechanism underlying the neuropathy. Chaperones can assemble in multi-chaperone complexes forming an integrative chaperone network in the cell, which plays relevant cellular roles in a variety of processes such as the correct folding of newly synthesized proteins, their escort to their precise cellular locations to form functional proteins and complexes and the response to protein misfolding, including the degradation of proteins that fail to refold properly. Despite of this variety of functions, mutations in some of them lead to diseases with a similar clinical picture, suggesting common pathways. This review gives an overview of the genetics of dHMNs caused by mutations in four genes, DNAJB2, HSPB1, HSPB3 and HSPB8, which encode chaperones and show a common disease mechanism.

  14. McCune-Albright syndrome: a detailed pathological and genetic analysis of disease effects in an adult patient.

    Science.gov (United States)

    Vasilev, Vladimir; Daly, Adrian F; Thiry, Albert; Petrossians, Patrick; Fina, Frederic; Rostomyan, Liliya; Silvy, Monique; Enjalbert, Alain; Barlier, Anne; Beckers, Albert

    2014-10-01

    McCune Albright syndrome (MAS) is a clinical association of endocrine and nonendocrine anomalies caused by postzygotic mutation of the GNAS1 gene, leading to somatic activation of the stimulatory α-subunit of G protein (Gsα). Important advances have been made recently in describing pathological characteristics of many MAS-affected tissues, particularly pituitary, testicular, and adrenal disease. Other rarer disease related features are emerging. The objective of the investigation was to study the pathological and genetic findings of MAS on a tissue-by-tissue basis in classically and nonclassically affected tissues. This was a comprehensive autopsy and genetic analysis. The study was conducted at a tertiary referral university hospital. An adult male patient with MAS and severe disease burden including gigantism was the subject of the study. Interventions included clinical, hormonal, and radiographic studies and gross and microscopic pathology analyses, conventional PCR, and droplet digital PCR analyses of affected and nonaffected tissues. Pathological findings and the presence of GNAS1 mutations were measured. The patient was diagnosed with MAS syndrome at 6 years of age based on the association of café-au-lait spots and radiological signs of polyostotic fibrous dysplasia. Gigantism developed and hyperprolactinemia, hypogonadotropic hypogonadism, and hyperparathyroidism were diagnosed throughout the adult period. The patient died at the age of 39 years from a pulmonary embolism. A detailed study revealed mosaiscism for the p.R201C GNAS1 mutation distributed across many endocrine and nonendocrine tissues. These genetically implicated tissues included rare or previously undescribed disease associations including primary hyperparathyroidism and hyperplasia of the thymus and endocrine pancreas. This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the

  15. Polyostotic Fibrous Dysplasia With and Without McCune–Albright Syndrome—Clinical Features in a Nordic Pediatric Cohort

    Directory of Open Access Journals (Sweden)

    Pauliina Utriainen

    2018-03-01

    Full Text Available ObjectiveFibrous dysplasia (FD presents as skeletal lesions in which normal bone is replaced by abnormal fibrous tissue due to mosaic GNAS mutation. McCune–Albright syndrome (MAS refers to FD combined with skin (café-au-lait and endocrine manifestations. This study describes the clinical childhood manifestations of polyostotic FD and MAS in a Nordic cohort.Patients and designWe retrospectively reviewed a cohort of pediatric patients (n = 16 with polyostotic FD with or without MAS diagnosed and followed in two Nordic Pediatric tertiary clinics between 1996 and 2017.ResultsHalf of the 16 patients with polyostotic FD presented with MAS. All patients with MAS (n = 8 had café-au-lait spots, and either gonadotropin-independent precocious puberty (PP (girls; n = 5 or abnormal testicle structure (boys, n = 3. None manifested hyperthyroidism or growth hormone excess. Mild hypophosphatemia was common (11/16, but none had signs of hypophosphatemic rickets. Craniofacial bone involvement was found in 12 patients (75%; in 5 of these, skeletal lesions were limited to craniofacial area. One child with craniofacial disease had lost vision due to optic nerve damage. Eleven (69% patients had sustained a fracture at FD lesion, over half of them requiring surgical fixation of the fracture, most commonly in the proximal femur. The first symptoms leading to FD/MAS diagnosis included skull/facial asymmetry (n = 4, PP (n = 3, abnormal gait (n = 3, pathologic fracture (n = 3, wide-spread café-au-lait spots (n = 1, headache (n = 1, and vision loss (n = 1.ConclusionPolyostotic FD and MAS remain diagnostic and therapeutic challenges because of the broad clinical spectrum. Recurrent fractures, pain, and even vision loss may impair the quality of life in children with FD.

  16. Blocking protein quality control to counter hereditary cancers

    DEFF Research Database (Denmark)

    Kampmeyer, Caroline; Nielsen, Sofie V.; Clausen, Lene

    2017-01-01

    cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although...... by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes....

  17. Management of women at high risk of hereditary breast cancer in the Veneto Regional Program for Prevention.

    Science.gov (United States)

    Del Sole, Annamaria; Cinquetti, Sandro; Fedato, Chiara; Montagna, Marco; Russo, Francesca; Sbrogiò, Luca Gino; Zorzi, Manuel

    2015-01-01

    Today it is well-known that high risk of genetic breast cancer concerns a very limited part of the population: no more than 2-3 women are affected every thousand and this condition as a whole accounts for no more than 3%-5% of all breast cancers. Following the directions contained in the 2014-2018 National Prevention Plan, Veneto's 2014-2018 Regional Program of Prevention (PRP), approved by Regional Council Resolution (DGR) No. 749 of 14.5.2015, consolidation of a pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma is thus proposed. The principal activities of this policy will be the following: creation of a regional working group, survey of currently existing pathways for the identification of women at risk of hereditary breast cancer and adoption of the same, approval and consolidation of a structured regional pathway for women at high risk of hereditary breast and/or ovarian cancer, from paths of oncogenetic consultation and genetic testing to management of disease risk. Subsequent to the recognition of the pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma, the Veneto region undertakes to develop a co-ordinated program of information and training on this pathway directed at the population and healthcare workers. It is firmly hoped that with the inclusion of a program for the management of women at high risk of hereditary breast cancer within the Veneto PRP this topic may become more defined and structured in terms of sustainability, integration with the existing regional networks (mammography network, Breast Unit), contrasting inequality, monitoring and evaluation, in this way pursuing the objectives of a reduction of cause-specific mortality and improvement of quality of life.

  18. Hereditary Breast Cancer: Mutations Within BRCA1 and BRCA2 with Phenotypic Responses

    National Research Council Canada - National Science Library

    Lynch, Henry T

    2000-01-01

    To date we have seventy-three Hereditary Breast/Ovarian Cancer families with identified BRCA1 or BRCA2 genetic mutations, wherein 24 additional cases of slides and tissue blocks have been retrieved...

  19. Functional C1-inhibitor diagnostics in hereditary angioedema: Assay evaluation and recommendations

    NARCIS (Netherlands)

    Wagenaar-Bos, Ineke G. A.; Drouet, Christian; Aygoeren-Pursun, Emel; Bork, Konrad; Bucher, Christoph; Bygum, Anette; Farkas, Henriette; Fust, George; Gregorek, Hanna; Hack, C. Erik; Hickey, Alaco; Joller-Jemelka, Helen I.; Kapusta, Maria; Kreuz, Wolfhart; Longhurst, Hilary; Lopez-Trascasa, Margarita; Madalinski, Kazimierz; Naskalski, Jerzy; Nieuwenhuys, Ed; Ponard, Denise; Truedsson, Lennart; Varga, Lilian; Nielsen, Erik Waage; Wagner, Eric; Zingale, Lorenza; Cicardi, Marco; van Ham, S. Marieke

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor Cl esterase inhibitor (C1-Inh). In addition to

  20. Urinary tract cancer and hereditary nonpolyposis colorectal cancer : Risks and screening options

    NARCIS (Netherlands)

    Sijmons, RH; Kiemeney, LALM; Witjes, JA; Vasen, HFA

    Purpose: We investigate the risk of the different types of urinary tract cancer in hereditary nonpolyposis colorectal cancer families and review screening options. Materials and Methods: We retrospectively calculated the relative and cumulative risks of developing urinary tract cancer by comparing

  1. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    DEFF Research Database (Denmark)

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  2. Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant.

    Science.gov (United States)

    Krause, Karoline; Metz, Martin; Zuberbier, Torsten; Maurer, Marcus; Magerl, Markus

    2010-04-01

    The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.

  3. Family history record and hereditary cancer risk perception according to National Cancer Institute criteria in a Spanish medical oncology service: a retrospective study.

    Science.gov (United States)

    Márquez-Rodas, Iván; López-Trabada, Daniel; Rupérez Blanco, Ana Belén; Custodio Cabello, Sara; Peligros Gómez, María Isabel; Orera Clemente, María; Calvo, Felipe A; Martín, Miguel

    2012-01-01

    Identification of patients at risk of hereditary cancer is an essential component of oncology practice, since it enables clinicians to offer early detection and prevention programs. However, the large number of hereditary syndromes makes it difficult to take them all into account in daily practice. Consequently, the National Cancer Institute (NCI) has suggested a series of criteria to guide initial suspicion. It was the aim of this study to assess the perception of the risk of hereditary cancer according to the NCI criteria in our medical oncology service. We retrospectively analyzed the recordings of the family history in new cancer patients seen in our medical oncology service from January to November 2009, only 1 year before the implementation of our multidisciplinary hereditary cancer program. The family history was recorded in only 175/621 (28%) patients. A total of 119 (19%) patients met 1 or more NCI criteria (1 criterion, n = 91; 2 criteria, n = 23; 3 criteria, n = 4; and 4 criteria, n = 1), and only 14 (11.4%) patients were referred to genetic counseling. This study shows that few clinicians record the family history. The perception of the risk of hereditary cancer is low according to the NCI criteria in our medical oncology service. These findings can be explained by the lack of a multidisciplinary hereditary cancer program when the study was performed. Copyright © 2012 S. Karger AG, Basel.

  4. Ethical dilemmas in genetic testing: examples from the Cuban program for predictive diagnosis of hereditary ataxias.

    Science.gov (United States)

    Mariño, Tania Cruz; Armiñán, Rubén Reynaldo; Cedeño, Humberto Jorge; Mesa, José Miguel Laffita; Zaldivar, Yanetza González; Rodríguez, Raúl Aguilera; Santos, Miguel Velázquez; Mederos, Luis Enrique Almaguer; Herrera, Milena Paneque; Pérez, Luis Velázquez

    2011-06-01

    Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series of five cases involving predictive testing for hereditary ataxias in Cuba. The examples herein present evidence of the deeply controversial situations faced by both individuals at risk and professionals in charge of these predictive studies, suggesting a need for expanded guidelines to address such complexities.

  5. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  6. Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis.

    Science.gov (United States)

    Giavina-Bianchi, Pedro; Arruda, Luisa Karla; Aun, Marcelo V; Campos, Regis A; Chong-Neto, Herberto J; Constantino-Silva, Rosemeire N; Fernandes, Fátima R; Ferraro, Maria F; Ferriani, Mariana P L; França, Alfeu T; Fusaro, Gustavo; Garcia, Juliana F B; Komninakis, Shirley; Maia, Luana S M; Mansour, Eli; Moreno, Adriana S; Motta, Antonio A; Pesquero, João B; Portilho, Nathalia; Rosário, Nelson A; Serpa, Faradiba S; Solé, Dirceu; Takejima, Priscila; Toledo, Eliana; Valle, Solange O.R; Veronez, Camila L; Grumach, Anete S

    2018-01-01

    Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the "Associação Brasileira de Alergia e Imunologia (ASBAI)" and the "Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)" has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

  7. Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract.

    Science.gov (United States)

    He, Wei; Li, Xin; Chen, Jiajing; Xu, Ling; Zhang, Feng; Dai, Qiushi; Cui, Hao; Wang, Duen-Mei; Yu, Jun; Hu, Songnian; Lu, Shan

    2011-03-01

    The aim of the study was to characterize the underlying mutation in a large multiplex Chinese family with hereditary nuclear cataract. A 6-generation Chinese family having hereditary nuclear cataract was recruited and clinically verified. Blood DNA samples were obtained from 53 available family members. Linkage analyses were performed on the known candidate regions for hereditary cataract with 36 polymorphic microsatellite markers. To identify mutations related to cataract, a direct sequencing approach was applied to a candidate gene residing in our linkage locus. A linkage locus was identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0) at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all affected family members. This transitional mutation resulted in a replacement of aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of the protein. The D47N mutation of Cx50 causes the hereditary nuclear cataract in this family in an autosomal dominant mode of inheritance with incomplete penetrance.

  8. Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract

    DEFF Research Database (Denmark)

    Hansen, Lars; Mikkelsen, Annemette; Nürnberg, Peter

    2009-01-01

    , and a gene conversion is the most likely mutational event causing this variant. Ten families had microcornea cataract, and a mutation was identified in eight of those. Most families displayed mixed phenotypes with nuclear, lamellar, and polar opacities and no apparent genotype-phenotype correlation emerged......PURPOSE: Identification of the causal mutations in 28 unrelated families and individuals with hereditary congenital cataract identified from a national Danish register of hereditary eye diseases. Seven families have been published previously, and the data of the remaining 21 families are presented...... together with an overview of the results in all families. METHODS: A combined screening approach of linkage analysis and sequencing of 17 cataract genes were applied to mutation analyses of total 28 families. RESULTS: The study revealed a disease locus in seven of eight families that were amenable...

  9. [Hereditary motor and sensory neuropathy type 4A].

    Science.gov (United States)

    Shagina, O A; Dadali, E L; Fedotov, V P; Tiburkova, T B; Poliakov, A V

    2010-01-01

    The first in the Russian Federation clinical cases of patients with autosomal-recessive type of hereditary motor and sensory neuropathy, type 4A, (HMSN 4A) are presented. In all cases, the diagnosis has been verified using molecular-genetic methods (DNA diagnostics). An analysis of features of clinical manifestations was performed in patients, aged from 5 to 34 years, with different disease duration (from 3-to 29 years). Criteria of selection of patients for DNA diagnostics for searching mutations in the GDAP1 gene are specified.

  10. [Mutation analysis of FGFR3 gene in a family featuring hereditary dwarfism].

    Science.gov (United States)

    Zhang, Qiong; Jiang, Hai-ou; Quan, Qing-li; Li, Jun; He, Ting; Huang, Xue-shuang

    2011-12-01

    To investigate the clinical symptoms and potential mutation in FGFR3 gene for a family featuring hereditary dwarfism in order to attain diagnosis and provide prenatal diagnosis. Five patients and two unaffected relatives from the family, in addition with 100 healthy controls, were recruited. Genome DNA was extracted. Exons 10 and 13 of the FGFR3 gene were amplified using polymerase chain reaction (PCR). PCR products were sequenced in both directions. All patients had similar features including short stature, short limbs, lumbar hyperlordosis but normal craniofacial features. A heterozygous mutation G1620T (N540K) was identified in the cDNA from all patients but not in the unaffected relatives and 100 control subjects. A heterozygous G380R mutation was excluded. The hereditary dwarfism featured by this family has been caused by hypochondroplasia (HCH) due to a N540K mutation in the FGFR3 gene.

  11. Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

    International Nuclear Information System (INIS)

    Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee

    2012-01-01

    Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

  12. Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee [Dept. of Radiology, Inha University Hospital, Incheon (Korea, Republic of)

    2012-03-15

    Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

  13. Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Suemori

    2015-01-01

    Full Text Available Flow cytometric test for analyzing the eosin-5-maleimide (EMA binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS. However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP and Southeast Asian ovalocytosis (SAO, which are forms in the category of hereditary elliptocytosis (HE, show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF cut-off value of 36.4 (sensitivity 0.97, specificity 0.95. Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.

  14. Genetics Home Reference: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis

    Science.gov (United States)

    ... Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis Printable PDF Open All Close All Enable Javascript ... Fibrosing Poikiloderma with Tendon Contractures, Myopathy, and Pulmonary ... Lung, and Blood Institute (NHLBI): Pulmonary Function Tests National ...

  15. Hereditary hypohidrotic ectodermal dysplasia: report of a rare case.

    Science.gov (United States)

    Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

    2013-09-01

    Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition.

  16. Hereditary spastic paraplegias: membrane traffic and the motor pathway

    OpenAIRE

    Blackstone, Craig; O’Kane, Cahir J.; Reid, Evan

    2011-01-01

    Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent wo...

  17. Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV

    Directory of Open Access Journals (Sweden)

    Yakup Ergül

    2011-01-01

    Full Text Available Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

  18. Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV.

    Science.gov (United States)

    Ergül, Yakup; Ekici, Bariş; Keskin, Sabiha

    2011-01-01

    Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

  19. Ultrastructural evaluation of gingival connective tissue in hereditary gingival fibromatosis.

    Science.gov (United States)

    Pêgo, Sabina Pena B; de Faria, Paulo Rogério; Santos, Luis Antônio N; Coletta, Ricardo D; de Aquino, Sibele Nascimento; Martelli-Júnior, Hercílio

    2016-07-01

    To describe the ultrastructural features of hereditary gingival fibromatosis (HGF) in affected family members and compare microscopic findings with normal gingival (NG) tissue. Gingival tissue samples from nine patients with HGF from five unrelated families were evaluated by transmission electron microscopy. Nine NG tissue samples were used for comparison. Areas containing collagen fibrils forming loops and folds were observed in both groups, whereas oxytalan fibers were frequently identified in the HGF group. The diameter of collagen fibrils and the interfibrillar space among them were more uniform in the NG group than in the HGF group. Fibroblasts were the most common cells found in both the HGF and NG groups and exhibited enlarged, rough endoplasmic reticulum, mitochondria with well-preserved crests, conspicuous nucleoli, and euchromatic chromatin. Other cells, such as mast cells, plasma cells, and macrophages, were also observed. HGF tissues had ultrastructural characteristics that were very similar to those of NG tissues. Oxytalan fibers were observed more frequently in the HGF samples than in the NG samples. Other studies of HGF in patients from different families should be performed to better understand the pathogenesis of this hereditary condition. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Laparoscopic splenectomy for hereditary spherocytosis-preliminary report.

    Science.gov (United States)

    Rogulski, Robert; Adamowicz-Salach, Anna; Matysiak, Michał; Piotrowski, Dariusz; Gogolewski, Michał; Piotrowska, Anna; Roik, Danuta; Kamiński, Andrzej

    2016-06-01

    Splenectomy is considered standard surgical therapy in hereditary spherocytosis. The procedure is indicated in patients with severe anemia, recurrent hemolytic, and aplastic crises. The aim of the study was to assess treatment outcomes in patients with hereditary spherocytosis who underwent total or partial laparoscopic splenectomy. Fifteen patients aged 4-17 yr underwent laparoscopic splenectomy from 2009 to 2012. Partial and total splenectomies were performed (five and 10 children, respectively). Hematologic parameters, liver function tests, and splenic volume before and after the surgery were analyzed retrospectively. Total follow-up was 1-30 months. Hospitalization and operating time were similar in both groups. In partial splenectomy group, branches of splenic arteries gave better blood supply than short gastric vessels. In both groups, hematologic parameters were improved. Postoperative markedly elevated platelet count was maintained up to 6 months, and after that, platelet count gradually decreased to normal values. Bilirubin level was decreased in early postoperative period; however, it increased later to achieve levels lower than in preoperative period. No severe general infections were observed in both groups. Laboratory parameters (hemoglobin and bilirubin concentrations and RBC) after the surgery improved in all patients, and the effect was maintained during 12 months of follow-up. Platelet count increased significantly after the surgery and was maintained at high levels during the next 6 months. However, it returned to preoperative levels within a year after the surgery. Our study showed that partial splenectomy was not inferior to total splenectomy. However, full assessment requires longer follow-up and larger group of patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Role of stretch therapy in comprehensive physical habilitation of patients with Charcot–Marie–Tooth hereditary neuropathy

    Directory of Open Access Journals (Sweden)

    N. A. Shnayder

    2015-01-01

    Full Text Available Charcot–Marie–Tooth hereditary neuropathy (Charcot–Marie–Tooth disease, CMT is the most common form of hereditary neuropathies, accompanied by sensory disorders, progressive muscle weakness with the formation of disabling contractures of the limbs. Currently, the main treatment program is effective CMT habilitation, which can prevent the development of limb deformities and thereby improve the life quality of the patient. Stretch therapy is one of the most effective methods of prevention and treatment of contractures in patients with CMT. This article provides a brief review of the literature regarding the use of stretching as physical therapy program of CMT habilitation.

  2. Converging cellular themes for the hereditary spastic paraplegias.

    Science.gov (United States)

    Blackstone, Craig

    2018-05-10

    Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes. Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking. Published by Elsevier Ltd.

  3. Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy

    DEFF Research Database (Denmark)

    Vestergaard, Nanna; Rosenberg, Thomas; Torp-Pedersen, Christian

    2017-01-01

    Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients. Methods...... patients (RR: 4.26, 95% CI: 1.91-9.48; P neuropathy, and alcohol-related disorders. Conclusions: The manifestation of LHON was associated...

  4. Hereditary sensory neuropathy type I

    Directory of Open Access Journals (Sweden)

    Auer-Grumbach Michaela

    2008-03-01

    Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

  5. Hereditary sensory neuropathy type I.

    Science.gov (United States)

    Auer-Grumbach, Michaela

    2008-03-18

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

  6. HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

    Directory of Open Access Journals (Sweden)

    A. A. Chernova

    2011-01-01

    Full Text Available Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG, echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

  7. Genetic disorder in carbohydrates metabolism: hereditary fructose intolerance associated with celiac disease.

    Science.gov (United States)

    Păcurar, Daniela; Leşanu, Gabriela; Dijmărescu, Irina; Ţincu, Iulia Florentina; Gherghiceanu, Mihaela; Orăşeanu, Dumitru

    2017-01-01

    Celiac disease (CD) has been associated with several genetic and immune disorders, but association between CD and hereditary fructose intolerance (HFI) is extremely rare. HFI is an autosomal recessive disease caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase). We report the case of a 5-year-old boy suffering from CD, admitted with an initial diagnosis of Reye's-like syndrome. He presented with episodic unconsciousness, seizures, hypoglycemia, hepatomegaly and abnormal liver function. The patient has been on an exclusion diet for three years, but he still had symptoms: stunting, hepatomegaly, high transaminases, but tissue transglutaminase antibodies were negative. Liver biopsy showed hepatic steatosis and mitochondrial damage. The dietary history showed an aversion to fruits, vegetables and sweet-tasting foods. The fructose tolerance test was positive, revealing the diagnostic of hereditary fructose intolerance. Appropriate dietary management and precautions were recommended. The patient has been symptom-free and exhibited normal growth and development until 10 years of age.

  8. Hereditary gingival fibromatosis: A report of two cases in the same family

    Directory of Open Access Journals (Sweden)

    Vanali V Umrania

    2016-01-01

    Full Text Available Overgrowth of keratinized gingival tissues is a common condition and is described under variety of names. Causes of such enlargement can be medications, hereditary, and/or local irritating factors. Mutation in SOS1, son-of-sevenless gene, is thought to be responsible for hereditary gingival fibromatosis. This report shows a case of 19-year-old male and his 15-year-old sister, with a chief complaint of overgrowth of gingival and irregularly placed teeth. A similar overgrowth was also found in other members of the same family, without any drug history or syndromic conditions. An occurrence of the disease has been found in two generations of this family and therefore, it may be following autosomal dominant trait of inheritance. Since it is idiopathic and has a genetic cause for its occurrence, it cannot be prevented. Both cases underwent a surgical intervention to rectify the abnormality and were followed from 6 months to 1 year, during which there was no recurrence.

  9. FROM FAMILIES SYNDROMES TO GENES… THE FIRST CLINICAL AND GENETIC CHARACTERIZATIONS OF HEREDITARY SYNDROMES PREDISPOSING TO CANCER: WHAT WAS THE BEGINNING?

    Directory of Open Access Journals (Sweden)

    Charité Ricker, MS, LCGC

    2017-07-01

    Full Text Available Assessment for hereditary susceptibility to cancer is considered standard of care, as it impacts not only a clinician's understanding of cancer causation but also options for prevention and treatment. The roots of our current knowledge about hereditary cancer syndromes can be traced to early reports of families with striking cancer histories. The purpose of this article is to review the historical timeline of the two most commonly assessed hereditary cancer syndromes, hereditary breast and ovarian cancer (HBOC and Lynch syndrome (LS. While many individuals identified with these syndromes today come from families similar to those seen in the early historical reports, our understanding of these syndromes, their expression and penetrance, has evolved over the years. In addition, the increased utilization of broad multi-gene panels continues to add to the complexity of defining associated phenotypes. These findings can lead to challenges with translating results to clinical management for patients and families, but also provide an opportunity to continue to gain understanding of the genetic underpinnings of cancer etiology.

  10. Imaging of Hereditary Hemorrhagic Telangiectasia

    International Nuclear Information System (INIS)

    Carette, Marie-France; Nedelcu, Cosmina; Tassart, Marc; Grange, Jean-Didier; Wislez, Marie; Khalil, Antoine

    2009-01-01

    This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.

  11. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.

    Science.gov (United States)

    Wells, Samuel A; Gosnell, Jessica E; Gagel, Robert F; Moley, Jeffrey; Pfister, David; Sosa, Julie A; Skinner, Michael; Krebs, Annetta; Vasselli, James; Schlumberger, Martin

    2010-02-10

    PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

  12. Hereditary protein S deficiency presenting with cerebral sinus thrombosis in an adolescent girl

    NARCIS (Netherlands)

    Koelman, J. H.; Bakker, C. M.; Plandsoen, W. C.; Peeters, F. L.; Barth, P. G.

    1992-01-01

    A 14-year-old girl, on oral contraceptives for 3 months, presented with cerebral sinus thrombosis. Investigation revealed underlying hereditary protein S deficiency. This uncommon cause of cerebral sinus thrombosis and the possible association with oral contraceptives are discussed

  13. Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal).

    Science.gov (United States)

    Spínola, Carla; Brehm, António; Spínola, Hélder

    2011-01-01

    Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that results from mutations in the HFE gene. Almost all patients with hereditary hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to hereditary hemochromatosis. One hundred and fifty-four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y, and S65C, by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33%, and 1% for H63D, C282Y, and S65C, respectively. Accordingly to our estimates, both genotypes associated to hereditary hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.

  14. Liberation Tigers of Tamil Elam, Aum Shinrikyo, Al Qaeda, and the Syrian Crisis: Nonstate Actors Acquiring WMD

    Science.gov (United States)

    2013-12-01

    Future of Lethal Gases That Threaten Our World (Santa Barbara, CA: Praeger, 2010), 126–127; David Bamber, Chris Hastings, and Rajeev Syal, “Bin...86 David Albright and Holly Higgins , “Pakistani Nuclear Scientists: How Much Nuclear Assistance to Al Qaeda?” August 30, 2002, Institute...6, 2002. Nautilus Institute. http://www.nautilus.org/archives/for a/Special-Policy-Forum/47_Albright.html. Albright, David and Holly Higgins

  15. Human parvovirus B19-induced aplastic crisis in an adult patient with hereditary spherocytosis: a case report and review of the literature.

    Science.gov (United States)

    Kobayashi, Yujin; Hatta, Yoshihiro; Ishiwatari, Yusaku; Kanno, Hitoshi; Takei, Masami

    2014-03-11

    Although there are several case reports of human parvovirus B19 infection in patients with hereditary spherocytosis, no systematic reviews of adult patients with hereditary spherocytosis with human parvovirus B19 infection have been published as clinical case reports. In this study, we report a case of aplastic crisis due to human parvovirus B19 infection in an adult patient with hereditary spherocytosis. A 33-year-old woman with hereditary spherocytosis and gallstones was admitted because of rapid progress in marked anemia and fever. Although empiric antibiotic therapy was prescribed, her clinical symptoms and liver function test worsened. Because the anti-human parvovirus B19 antibody and deoxyribonucleic acid levels assessed by polymerase chain reaction were positive, the patient was diagnosed with aplastic crisis due to the human parvovirus B19 infection. We collected and reviewed several case reports of patients with hereditary spherocytosis aged > 18 years with human parvovirus B19 infection between 1984 and 2010. A total of 19 reports with 22 cases [median age, 28 years (range, 18-43 range); male: female ratio, 6:16], including the present case were identified. The male-to-female ratio of 6:16 implied that younger females were predominantly affected. Although fever and abdominal symptoms were common initial symptoms, liver dysfunction or skin eruptions were less commonly documented. Anti-human parvovirus B19 antibody or deoxyribonucleic acid levels assessed by polymerase chain reaction was commonly used to diagnose human parvovirus B19 infection and may be useful to distinguish human parvovirus B19 infection from other abdominal infection in patients with hereditary spherocytosis.

  16. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered ica...

  17. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing

    DEFF Research Database (Denmark)

    Rohlin, Anna; Rambech, Eva; Kvist, Anders

    2017-01-01

    Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel...

  18. Clinical definition of hereditary non-polyposis colorectal cancer : A search for the impossible?

    NARCIS (Netherlands)

    Berends, MJW; Wu, Y; Sijmons, RH; Hofstra, RMW; van der Zee, AGJ; Buys, CHCM; Kleibeuker, JH

    2001-01-01

    Hereditary non-polyposis colorectal cancer is an autosomal dominant inherited disorder that predisposes its carriers to an almost 100% lifetime risk of cancer, in particular colorectal and endometrial cancer. Germline mutations, resulting in a deficient DNA mismatch repair system. are responsible

  19. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

    Directory of Open Access Journals (Sweden)

    Annegret Müller

    2004-01-01

    Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.

  20. Hereditary cancer genes are highly susceptible to splicing mutations

    Science.gov (United States)

    Soemedi, Rachel; Maguire, Samantha; Murray, Michael F.; Monaghan, Sean F.

    2018-01-01

    Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5′ and 3′ splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36%) of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing. PMID:29505604

  1. Hereditary cancer genes are highly susceptible to splicing mutations.

    Directory of Open Access Journals (Sweden)

    Christy L Rhine

    2018-03-01

    Full Text Available Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77% of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36% of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing.

  2. Radiobiology in clinical radiation therapy: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

    International Nuclear Information System (INIS)

    Brenner, David J.

    1997-01-01

    The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

  3. [Hereditary haemorrhagic telangiectasia diagnosed in connection with a traffic accident].

    Science.gov (United States)

    Sivapalan, Pradeesh; Demény, Ann Kathrin; Almind, Merete; Kjeldsen, Anette Drøhse

    2014-02-17

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular dysplasia and haemorrhage. It is manifested by mucocutaneous telangiec-tases and arteriovenous malformations in organs such as lungs, liver and brain. We present a case of HHT. A 16-year-old patient with a history of recurrent epistaxis was admitted to the local hospital with chest pain and desaturation. A CT scan revealed pulmonary arteriovenous malformations.

  4. A long-term follow-up study of subtotal splenectomy in children with hereditary spherocytosis

    NARCIS (Netherlands)

    Rosman, Colin; Broens, P M A; Trzpis, M; Tamminga, R Y J

    2017-01-01

    BACKGROUND: Hereditary spherocytosis (HS) is a heterogeneous hemolytic anemia treated with splenectomy in patients suffering from severe or moderate disease. Total splenectomy, however, renders patients vulnerable to overwhelming postsplenectomy infection despite preventive measures. Although

  5. An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations

    DEFF Research Database (Denmark)

    Timshel, Susanne; Therkildsen, Christina; Bendahl, Pär-Ola

    2009-01-01

    Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC......). We specifically addressed anticipation in phenotypic HNPCC families without disease-predisposing mismatch repair (MMR) defects since risk estimates and age at onset are particularly difficult to determine in this cohort. The national Danish HNPCC register was used to identify families who fulfilled...... the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated...

  6. Índices eritrocitarios en la esferocitosis hereditaria Erythrocyte indexes in hereditary spherocytosis

    Directory of Open Access Journals (Sweden)

    Silvia Eandi Eberle

    2007-12-01

    Full Text Available La esferocitosis hereditaria es un grupo heterogéneo de desórdenes caracterizados por la variabilidad en la clínica, en los defectos proteicos del citoesqueleto eritrocitario y en el tipo de herencia. Se estudió la sensibilidad y especificidad de la concentración de hemoglobina corpuscular media (CHCM y el índice de amplitud de distribución eritrocitaria (ADE en el screening diagnóstico de la esferocitosis hereditaria. Noventa y cuatro pacientes fueron comparados con niños sanos de igual sexo y edad. Todos los índices se obtuvieron por impedancia eléctrica (autoanalizador hematológico Coulter JT. En los pacientes con esferocitosis hereditaria, la CHCM (35.67±1.33 g/dl y el ADE (20.60±4.5%, fueron significativamente más elevados que en el grupo control (CHCM 33.48±0.68 g/dl, p 0.000; ADE 13.22±0.9%, p 0.000. Con los valores de corte utilizados en nuestro laboratorio (CHCM ≥ 34.5 g/dl; ADE ≥ 14.5% ambos índices elevados mostraron una sensibilidad de 81% y una especificidad de 98.9% en el screening de esferocitosis hereditaria. La combinación de ambos índices es un excelente predictor para el diagnóstico de esferocitosis hereditaria.Hereditary spherocytosis is a group of heterogenous disorders characterized by variability in its clinical manifestations, membrane protein defects and inheritance. We analysed the sensitivity and specificity of mean corpuscular hemoglobin concentration (MCHC and red cell distribution width (RDW in the diagnostic screening of hereditary spherocytosis. Ninetyfour patients were compared to equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance (Coulter Counter Model JT. In patients with hereditary spherocytosis, MCHC (35.67±1.33 g/dl and RDW (20.60±4.5% were significantly higher than in normal control subjects (MCHC 33.48±0.68 g/dl, p: 0.000; RDW 13.22±0.9%, p: 0.000. By using a cutoff for the MCHC of 34.5 g/dl and for the RDW

  7. Environmental Factors and Colorectal Tumor Risk in Individuals With Hereditary Nonpolyposis Colorectal Cancer

    NARCIS (Netherlands)

    Diergaarde, B.; Braam, H.; Vasen, H.F.; Nagengast, F.M.; Muijen, van G.N.P.; Kok, F.J.; Kampman, E.

    2007-01-01

    Background & Aims: Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) are at increased risk for colorectal cancer. Environmental factors might play a role in HNPCC-associated carcinogenesis. The aim of this study was to gain insight into the effects of environmental factors on

  8. Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

    NARCIS (Netherlands)

    Bohus, B.; Wimersma Greidanus, T.B. van; Wied, D. de

    Behavioral and endocrine profiles were established of homozygous (HO-DI) and heterozygous (HE-DI) rats with hereditary hypothalamic diabetes insipidus in comparison to Wistar strain rats. HO-DI rats were inferior in acquiring and maintaining active and passive avoidance behavior. Behavioral deficits

  9. The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Aben, K.K.H.; Oort, I.M. van; Sedelaar, J.P.M.; Vasen, H.F.A.; Vermeulen, S.H.; Kiemeney, L.A.L.M.

    2016-01-01

    BACKGROUND: The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form

  10. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1989-01-01

    in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages......Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  11. Deprivation amblyopia and congenital hereditary cataract.

    Science.gov (United States)

    Mansouri, Behzad; Stacy, Rebecca C; Kruger, Joshua; Cestari, Dean M

    2013-01-01

    Amblyopia is a neurodevelopmental disorder of vision associated with decreased visual acuity, poor or absent stereopsis, and suppression of information from one eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia), refractive error (anisometropic amblyopia), or deprivation from obstructed vision (deprivation amblyopia). 1 In the developed world, amblyopia is the most common cause of childhood visual impairment, 3 which reduces quality of life 4 and also almost doubles the lifetime risk of legal blindness.(5, 6) Successful treatment of amblyopia greatly depends on early detection and treatment of predisposing disorders such as congenital cataract, which is the most common cause of deprivational amblyopia. Understanding the genetic causes of congenital cataract leads to more effective screening tests, early detection and treatment of infants and children who are at high risk for hereditary congenital cataract.

  12. Knowledge about hereditary cancer of women with family histories of breast, colorectal, or both types of cancer.

    Science.gov (United States)

    Campacci, N; de Lima, J O; Ramadan, L; Palmero, E I

    2015-03-01

    Usually, the mass media do not address hereditary cancer and their risk factors, nor are these topics discussed at the community level. We used an informative guide on cancer and hereditary cancer, followed by a questionnaire on these topics to investigate the relevant knowledge among women at high risk for hereditary breast and/or colorectal cancer from a population-based cohort. The cohort was composed of 81 Brazilian women with positive family histories of breast and/or colorectal cancer. Strauss and Corbin's Grounded Theory was used for qualitative analysis. The average age of the cohort was 49.9 years old. Three participants (3.9%) were illiterate, 45 (59.2%) had attended elementary school, 14 (18.4%) had secondary school, and 14 (18.4%) held higher education degrees. A total of 47 (54.3%) volunteers were unable to fully understand the information provided in the guide because they did not know the meaning of words such as metastasis, malignant, hereditary, sporadic, or oncogenetics. Notwithstanding, the acceptance of the educational tool utilized was satisfactory, and it enhanced the volunteers' interest in a better understanding of cancer and heredity. Thereby, we concluded that the low knowledge of this important subject and the unawareness about fundamental terms required for the comprehension of this specific type of neoplasm made us believe that the use of the informative guide can provide a great value when used previously to the genetic counseling consultations. Besides, educational tools of easy understanding should be part of everyday clinical practice, from primary to specialized patient care.

  13. Gender specific issues in hereditary ocular disorders.

    Science.gov (United States)

    Iragavarapu, Saradha; Gorin, Michael B

    2015-02-01

    This review is intended to summarize the current knowledge from basic science and clinical medical literature cited within PubMed that pertain to gender-related factors and affect those individuals with hereditary ocular disorders. We consider gender-related biological factors that (a) affect disease onset and progression, (b) gender differences for major X-linked ocular disorders, (c) gender-specific conditions, (d) medications that may influence genetic eye disorders, and finally, (e) gender-related issues that influence the management and quality of life of these patients. Several studies have demonstrated the manner in which sex-related hormones in animal models are capable of influencing cell pathway and survival that are likely to affect hereditary eye disorders. There are very few clinical studies that provide compelling evidence for gender differences in human ocular conditions, other than for a number of X-linked disorders. Disease expression for X-linked disorders may be impacted by genetic mechanisms such as lyonization or uniparental disomy. Clinical evidence regarding the impact of gender-related medical conditions and therapies on eye conditions is extremely limited and primarily based on anecdotal evidence. Gender-specific factors may play a major role in the underlying biological pathways that influence the onset, rate of progression, and clinical findings associated with ocular genetic conditions. Clinicians need to be aware of the variable phenotypes observed in female carriers of X-linked disorders of gender specific issues, many of which are inadequately addressed in the current literature. Clinicians need to be sensitive to gender differences in social, cultural, and religious systems and they should also be aware of how their own gender biases may influence how they counsel patients. Finally, it is clear that the lack of effective clinical studies in this area creates an opportunity for future research that will have real benefits for these

  14. Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy.

    Directory of Open Access Journals (Sweden)

    Yadi Li

    Full Text Available Leber hereditary optic neuropathy (LHON and dominant optic atrophy (DOA, the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA (m.3460G>A, m.11778G>A and m.14484T>C. All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3% primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations, four at m.3460 (4/89, 4.5% and nine at m.14484 (9/89, 10.1%. This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age.

  15. Hereditary syndromes with enhanced radiosensitivity

    International Nuclear Information System (INIS)

    Lohmann, D.

    2000-01-01

    Sensitivity to ionizing radiation is modified by heritable genetic factors. This is exemplified by heritable disorders that are characterized by predisposition to the development of neoplasms. Cells derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome and ataxia telangiektasia-like disorder show a markedly changed reaction to exposure to ionizing radiation. Correspondingly, at least in patients with ataxia telangiectasia, an enhanced radiosensitivity that is of clinical importance has been observed. In addition to these recessive disorders, some autosomal dominant cancer predisposition syndromes are associated with increased radiosensitivity. As cells from these patients still have a normal allele (that is dominant over the mutant allele), the cellular phenotype is most often normal. Specifically, there is no overtly altered reaction in response to ionizing radiation. Nevertheless, two dominant cancer predisposition syndromes, namely hereditary retinoblastoma and naevoid basal cell carcinoma syndrome, are associated with a enhanced radiosensitivity as indicated by increased development of tumors following radiation therapy. (orig.) [de

  16. The Decrease in Mitochondrial DNA Mutation Load Parallels Visual Recovery in a Leber Hereditary Optic Neuropathy Patient

    Directory of Open Access Journals (Sweden)

    Sonia Emperador

    2018-02-01

    Full Text Available The onset of Leber hereditary optic neuropathy is relatively rare in childhood and, interestingly, the rate of spontaneous visual recovery is very high in this group of patients. Here, we report a child harboring a rare pathological mitochondrial DNA mutation, present in heteroplasmy, associated with the disease. A patient follow-up showed a rapid recovery of the vision accompanied by a decrease of the percentage of mutated mtDNA. A retrospective study on the age of recovery of all childhood-onset Leber hereditary optic neuropathy patients reported in the literature suggested that this process was probably related with pubertal changes.

  17. Genetic etiology of hereditary colorectal cancer: new mechanisms and advanced mutation detection techniques

    NARCIS (Netherlands)

    Gazzoli, I.

    2006-01-01

    The human DNA mismatch repair (MMR) system functions to repair mispaired bases in DNA that result from DNA replication errors and thereby prevents the accumulation of mutations due to such replication errors. Hereditary nonpolyposis colorectal cancer (HNPCC), the most common form of inherited colon

  18. Bilateral hereditary micro-epiphyseal dysplasia : clinical and genetic analysis of a Dutch family

    NARCIS (Netherlands)

    Mostert, Adrianus Klazinus

    2003-01-01

    This thesis is based upon a study of a Dutch family with a unique skeletal dysplasia first described by Elsbach in 1959. Because of the presence of microepiphyses, he called this disorder bilateral hereditary micro-epiphyseal dysplasia (BHMED) and distinguished it from more common multiple

  19. Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy

    Science.gov (United States)

    Wallace, Douglas C.; Singh, Gurparkash; Lott, Marie T.; Hodge, Judy A.; Schurr, Theodore G.; Lezza, Angela M. S.; Elsas, Louis J.; Nikoskelainen, Eeva K.

    1988-12-01

    Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

  20. Hereditary motor and sensory neuropathy Lom type in a Serbian family.

    Science.gov (United States)

    Dacković, J; Keckarević-Marković, M; Komazec, Z; Rakocević-Stojanović, V; Lavrnić, D; Stević, Z; Ribarić, K; Romac, S; Apostolski, S

    2008-10-01

    Hereditary motor and sensory neuropathy Lom type (HMSNL), also called CMT 4D, a hereditary autosomal recessive neuropathy, caused by mutation in N-Myc downstream regulated gene 1 (NDRG1 gene), was first described in a Bulgarian Gypsy population near Lom and later has been found in Gypsy communities in Italy, Spain, Slovenia and Hungary. We present two siblings with HMSNL, female and male, aged 30 and 26, respectively in a Serbian non-consanguineous family of Gypsy ethnic origin. They had normal developmental milestones. Both had symptoms of lower limb muscle weakness and walking difficulties with frequent falls, which began at the age of seven. At the age of 12, they developed hearing problems and at the age of 15 hand muscle weakness. Neurological examination revealed sensorineural hearing loss, dysarthria, severe distal and mild proximal muscle wasting and weakness, areflexia and impairment of all sensory modalities of distal distribution. Electrophysiological study revealed denervation with severe and early axonal loss. Sensorineural hearing loss was confirmed on electrocochleography and brainstem evoked potentials. Molecular genetic testing confirmed homozygote C564t (R148X) mutation in NDRG1 gene.

  1. Hereditary hemochromatosis (HFE) genotypes in heart failure: relation to etiology and prognosis

    DEFF Research Database (Denmark)

    Møller, Daniel Vega; Pecini, Redi; Gustafsson, Finn

    2010-01-01

    It is believed that hereditary hemochromatosis (HH) might play a role in cardiac disease (heart failure (HF) and ischemia). Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role...... and the prognostic significance of HFE genotypes....

  2. Treatment of Laryngeal Telangiectatic Lesions in a Patient Diagnosed with Hereditary Haemorrhagic Telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, Anette Drøhse; Printz, Trine; Slot Mehlum, Camilla

    2015-01-01

    Abstract We here present a case concerning a 69 year old female patient with Hereditary Haemorrhagic Telangiectasia (HHT). She was suffering from hoarseness due to a telangiectatic lesion on the right vocal cord. The lesion was treated with laser and the voice improved markedly, which is document...

  3. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    NARCIS (Netherlands)

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  4. [Hereditary sensory and autonomic neuropathy type II A: early neurological and skeletal findings].

    Science.gov (United States)

    Esmer, C; Díaz Zambrano, S; Santos Díaz, M A; González Huerta, L M; Cuevas Covarrubias, S A; Bravo Oro, A

    2014-04-01

    The hereditary sensory and autonomic neuropathies are genetic disorders characterized by the loss of sensation including pain, tactile and temperature. Its clinical and molecular features vary widely; the symptoms may begin from birth or be noticed in the first or second decade, with different types of complications of trauma to the extremities such as ulcers, mutilations and acral amputations. They are classified into six groups from I to VI, determined by the abnormality in eleven genes leading to phenotypic variations in the age of onset and the presence or absence of dysautonomia signs. With the exception of type I, all are autosomal recessive. The type II of these neuropathies is characterized by insensitivity to pain, heat and proprioception. We describe three members of a Mexican family with WNK1 gene mutation that caused hereditary neuropathy IIA. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  5. Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy

    Science.gov (United States)

    Klein, C; Dyck, P; Friedenberg, S; Burns, T; Windebank, A; Dyck, P

    2002-01-01

    Objective: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. Methods: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. Results: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. Conclusions: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders. PMID:12082044

  6. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Aygören-Pürsün E

    2016-09-01

    Full Text Available Emel Aygören-Pürsün,1 Anette Bygum,2 Kathleen Beusterien,3 Emily Hautamaki,4 Zlatko Sisic,5 Henrik B Boysen,6 Teresa Caballero7 1Angioedema Centre, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; 2Hereditary Angioedema Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; 3Outcomes Research Strategies in Health, Washington, DC, 4Patient Reported Outcomes, Oxford Outcomes Inc., an ICON plc company, Bethesda, MD, USA; 5ViroPharma Incorporated, Chatsworth House, Maidenhead, UK; 6HAEi – Hereditary Angioedema International Patient Organization for C1 Inhibitor Deficiencies, Skanderborg, Denmark; 7Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz, Biomedical Research Network on Rare Diseases U754 (CIBERER, University Hospital La Paz, Madrid, Spain Objective: To estimate health status utility (preference weights for hereditary angioedema (HAE during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation

  7. Hereditary stomatocytosis: association of low 2,3-diphosphoglycerate with increased cation pumping by the red cell.

    Science.gov (United States)

    Wiley, J S; Cooper, R A; Adachi, K; Asakura, T

    1979-01-01

    The levels of glycolytic intermediates have been measured in red cells from patients with both overhydrated and dehydrated varieties of the hereditary stomatocytosis syndrome. Red cell 2,3-diphosphoglycerate was reduced by 33% below normal in all patients with either stomatocyte or target cell morphologies (i.e. over or under hydrated varieties respectively). The relative decrement in 2,3-diphosphoglycerate was even greater when abnormal cells were compared with control cells with similar reticulocytosis. Red cell ADP concentrations in stomatocytosis were significantly increased above normal but ATP concentrations were not significantly changed. Whole blood oxygen affinity in stomatocytosis was increased in proportion to the lowered content of diphosphoglycerate. Some new parameters of membrane transport in hereditary stomatocytosis have been measured. Platelet K+ and Na+ concentrations and platelet K+ permeability were normal in stomatocytosis. The number of 3H-uridine transport sites in stomatocytes were increased by 9-39% above normal and this increment was the same as the increment in red cell lipids (0-38%). Hereditary stomatocytes contain 2-10-fold more cation pumps than normal and the increased active cation pumping may explain the high ADP, the low 2,3-diphosphoglycerate concentration and the increased oxygen affinity in this syndrome.

  8. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...

  9. Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    de Jong, Andrea E.; van Puijenbroek, Marjo; Hendriks, Yvonne; Tops, Carli; Wijnen, Juul; Ausems, Margreet G. E. M.; Meijers-Heijboer, Hanne; Wagner, Anja; van Os, Theo A. M.; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans F. A.; Morreau, Hans

    2004-01-01

    Immunohistochemistry (IHC) and microsatellite instability (MSI) analysis can be used to identify patients with a possible DNA mismatch repair defect [hereditary nonpolyposis colorectal carcinoma (HNPCC)]. The Bethesda criteria have been proposed to select families for determination of MSI. The aims

  10. Automated imaging dark adaptometer for investigating hereditary retinal degenerations

    Science.gov (United States)

    Azevedo, Dario F. G.; Cideciyan, Artur V.; Regunath, Gopalakrishnan; Jacobson, Samuel G.

    1995-05-01

    We designed and built an automated imaging dark adaptometer (AIDA) to increase accuracy, reliability, versatility and speed of dark adaptation testing in patients with hereditary retinal degenerations. AIDA increases test accuracy by imaging the ocular fundus for precise positioning of bleaching and stimulus lights. It improves test reliability by permitting continuous monitoring of patient fixation. Software control of stimulus presentation provides broad testing versatility without sacrificing speed. AIDA promises to facilitate the measurement of dark adaptation in studies of the pathophysiology of retinal degenerations and in future treatment trials of these diseases.

  11. [Hereditary hemorrhagic telangiectasia presenting with hematuria and severe anemia].

    Science.gov (United States)

    Paz, A; Goren, E; Segal, M

    1995-07-01

    A patient with hereditary hemorrhagic telangiectasia was admitted with hematuria and severe anemia after mild recurrent episodes of epistaxis. Telangiectasias were found in the skin and buccal and nasal mucosa. No defect in the coagulation mechanism was found; thrombocyte count and function were normal. On cystoscopy, tortuous engorged vessels, some actively bleeding, were seen in the trigonal mucosa. Biopsy showed enlarged vessels in the lamina propria. Electrocoagulation of the bleeding vessels stopped hematuria, but 6 months later it recurred. This time Nd-YAG laser was used to stop the bleeding after electrocoagulation was ineffective.

  12. Lamotrigine in the treatment of psychotic depression associated with hereditary coproporphyria -- case report and a brief review of the literature.

    Science.gov (United States)

    Takács, Rozália; Makkos, Zoltán; Kassai-Farkas, Ákos; Pusztai, Ágnes; Ungvári, Gábor S; Gazdag, Gábor

    2014-03-01

    We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. M.F., a 38-year-old, single woman was admitted to an acute psychiatric ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was diagnosed 9 years before the current admission. While on treatment with olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view of her significant mood fluctuations predominantly with depressed phases, lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow-up, while still on lamotrigine, her porphyria was asymptomatic. To the best of our knowledge, this is the first report about the safe administration of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute porphyric attack as confirmed by clinical and laboratory findings.

  13. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    Science.gov (United States)

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

  14. Serial casting for neuromuscular flatfoot and vertical talus in an adolescent with hereditary spastic paraplegia.

    Science.gov (United States)

    Sweet, Laurene A; OʼNeill, Lindsey M; Dobbs, Matthew B

    2014-01-01

    The purpose of this report is to explore assessment and serial casting intervention for painful rigid flatfoot deformities with vertical talus in an adolescent girl with hereditary spastic paraplegia who was nonambulatory. The participant's right foot underwent 2 phases of casting with correction first toward hindfoot inversion and then dorsiflexion. Because of a vertical talus, her left foot required an intermediate casting toward plantar flexion, inversion, and forefoot adduction prior to casting toward dorsiflexion. The patient improved despite the underlying progressive neuromuscular disorder. Pain ameliorated and she returned to supported standing and transfers. Spasticity decreased bilaterally and the flexibility of her foot deformities improved to allow orthotic fabrication in subtalar neutral. Results were maintained at 12 and 16 months. Individualized multiphase serial casting requires further investigation with patients such as those with hereditary spastic paraplegia.

  15. Dementia with non-hereditary cystatin C angiopathy

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Jóhannesson, G

    1989-01-01

    Brain biopsies from two patients with non-hereditary cerebral hemorrhages and eighty autopsied cases with the clinical diagnosis of dementia are presented. The biopsied cases, both males aged 64 and 59, had a sudden onset of cerebral hemorrhage, mild progressive dementia and cystatin C cerebral...... amyloid angiopathy. Of the autopsied cases 59 had senile plaques and cerebral amyloid angiopathy was also found in 36 of them. Both senile plaques and the blood vessel amyloid stained positively with beta-protein antibodies, and five of them also showed a positive reaction to cystatin C antibodies....... These cystatin C positive cases were three males aged 76, 80 and 83, and one female 93 years old and the fifth case was a female aged 47 with Down's syndrome....

  16. Current concepts in the treatment of hereditary ataxias

    Directory of Open Access Journals (Sweden)

    Pedro Braga Neto

    2016-03-01

    Full Text Available ABSTRACT Hereditary ataxias (HA represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

  17. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study

    NARCIS (Netherlands)

    Maat-Schieman, M. L.; Rozemuller, A. J.; van Duinen, S. G.; Haan, J.; Eikelenboom, P.; Roos, R. A.

    1994-01-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately

  18. Canine hereditary ataxia in old english sheepdogs and gordon setters is associated with a defect in the autophagy gene encoding RAB24.

    Directory of Open Access Journals (Sweden)

    Caryline Agler

    2014-02-01

    Full Text Available Old English Sheepdogs and Gordon Setters suffer from a juvenile onset, autosomal recessive form of canine hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex. The clinical and histological characteristics are analogous to hereditary ataxias in humans. Linkage and genome-wide association studies on a cohort of related Old English Sheepdogs identified a region on CFA4 strongly associated with the disease phenotype. Targeted sequence capture and next generation sequencing of the region identified an A to C single nucleotide polymorphism (SNP located at position 113 in exon 1 of an autophagy gene, RAB24, that segregated with the phenotype. Genotyping of six additional breeds of dogs affected with hereditary ataxia identified the same polymorphism in affected Gordon Setters that segregated perfectly with phenotype. The other breeds tested did not have the polymorphism. Genome-wide SNP genotyping of Gordon Setters identified a 1.9 MB region with an identical haplotype to affected Old English Sheepdogs. Histopathology, immunohistochemistry and ultrastructural evaluation of the brains of affected dogs from both breeds identified dramatic Purkinje neuron loss with axonal spheroids, accumulation of autophagosomes, ubiquitin positive inclusions and a diffuse increase in cytoplasmic neuronal ubiquitin staining. These findings recapitulate the changes reported in mice with induced neuron-specific autophagy defects. Taken together, our results suggest that a defect in RAB24, a gene associated with autophagy, is highly associated with and may contribute to canine hereditary ataxia in Old English Sheepdogs and Gordon Setters. This finding suggests that detailed investigation of autophagy pathways should be undertaken in human hereditary ataxia.

  19. Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography

    Energy Technology Data Exchange (ETDEWEB)

    Avni, Fred E.; Cassart, Marie; Massez, Anne [Erasme Hospital, Department of Medical Imaging, Brussels (Belgium); Garel, Laurent [Sainte Justine Hospital, Department of Paediatric Imaging, Montreal, Quebec (Canada); Eurin, Daniele [Charles Nicolle Hospital, Department of Paediatric Imaging, Rouen (France); Didier, Francois [A. Pinard Regional Maternity Hospital, Department of Paediatric Imaging, Nancy (France); Hall, Michelle [Erasme Hospital, Department of Pediatric Nephrology, Brussels (Belgium); Teele, Rita L. [Starship Children' s Hospital, Department of Radiology, Auckland (New Zealand)

    2006-05-15

    The aims of this review article were to clarify the steps that may lead to a proper diagnosis of fetal and neonatal renal cystic diseases. All the hereditary cystic diseases are reviewed and a classification is proposed. The various sonographic patterns that can be used to ascertain the diagnosis are also reviewed. Finally, tables with differential diagnoses are presented to help the reader in the work-up of such pathologies. (orig.)

  20. Life-threatening hereditary angio-oedema: Challenges of care in South Africa.

    Science.gov (United States)

    Potter, P; Peter, J

    2018-03-28

    The report and description by Coovadia et al.[1] in this issue of SAMJ of a large cohort of patients in the Western Cape Province of South Africa (SA) suffering from type 1 hereditary angio-oedema (HAE) not only documents for the first time a significant presence of this life-threatening condition on the African continent but highlights the challenges of diagnosis and management in the SA socioeconomic and healthcare context.

  1. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Møller, T R; Brusgaard, K

    2005-01-01

    BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically...... patients had experienced more severe GI bleeding than HHT2 patients. There was no significant difference in severity of epistaxis or age at debut. Finally the mortality over a 90-month observation period was not significantly increased....

  2. Hereditary Angioedema: The Economics of Treatment of an Orphan Disease.

    Science.gov (United States)

    Lumry, William Raymond

    2018-01-01

    This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

  3. Hereditary properties of Amenability modulo an ideal of Banach algebras

    Directory of Open Access Journals (Sweden)

    Hamidreza Rahimi

    2014-10-01

    Full Text Available In this paper we investigate some hereditary properties of amenability modulo an ideal of Banach algebras. We show thatif $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity modulo $I$ of a Banach algebra $A$ and $X$ is a neo-unital modulo $I$, then $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity for $X$. Moreover we show that amenability modulo an ideal of a Banach algebra $A$ can be only considered by the neo-unital modulo $I$ Banach algebra over $A$

  4. The burden of illness in patients with hereditary angioedema.

    Science.gov (United States)

    Banerji, Aleena

    2013-11-01

    Hereditary angioedema (HAE) is a rare genetic disease characterized by long-term recurrent attacks of subcutaneous or submucosal edema in different parts of the body. A comprehensive review of the literature on burden of illness for patients with HAE is presented. A Boolean search was performed using MEDLINE and EMBASE databases and the Internet. Articles discussing aspects of the burden of illness in HAE were selected. Topics focused on the course of the disease, nature of attacks, treatment, quality of life, and costs. Hereditary angioedema is associated with a significant and multifaceted disease burden. Diagnosis is often delayed for years, with patients receiving ineffective treatment and unnecessary medical procedures before diagnosis. HAE attacks are painful, unpredictable, and debilitating and often require emergency medical attention. Attacks can affect a patient's daily activities, including work or schooling. Depression and anxiety are prevalent in patients with HAE. Recent advances in treatment provide patients with effective and well-tolerated prophylactic and on-demand therapeutic options. However, end points specific to HAE that better measure the impact of treatment on disease burden are lacking. Furthermore, there is a notable paucity of literature directed toward physicians who are instrumental in diagnosing and treating patients with HAE (eg, emergency department). More publications are broadening the understanding of HAE. However, important gaps remain. Effective management of HAE requires a more comprehensive understanding of the disease burden so that disease management can be individualized to meet specific patient needs. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Fractional hereditariness of lipid membranes: Instabilities and linearized evolution.

    Science.gov (United States)

    Deseri, L; Pollaci, P; Zingales, M; Dayal, K

    2016-05-01

    In this work lipid ordering phase changes arising in planar membrane bilayers is investigated both accounting for elasticity alone and for effective viscoelastic response of such assemblies. The mechanical response of such membranes is studied by minimizing the Gibbs free energy which penalizes perturbations of the changes of areal stretch and their gradients only (Deseri and Zurlo, 2013). As material instabilities arise whenever areal stretches characterizing homogeneous configurations lie inside the spinoidal zone of the free energy density, bifurcations from such configurations are shown to occur as oscillatory perturbations of the in-plane displacement. Experimental observations (Espinosa et al., 2011) show a power-law in-plane viscous behavior of lipid structures allowing for an effective viscoelastic behavior of lipid membranes, which falls in the framework of Fractional Hereditariness. A suitable generalization of the variational principle invoked for the elasticity is applied in this case, and the corresponding Euler-Lagrange equation is found together with a set of boundary and initial conditions. Separation of variables allows for showing how Fractional Hereditariness owes bifurcated modes with a larger number of spatial oscillations than the corresponding elastic analog. Indeed, the available range of areal stresses for material instabilities is found to increase with respect to the purely elastic case. Nevertheless, the time evolution of the perturbations solving the Euler-Lagrange equation above exhibits time-decay and the large number of spatial oscillation slowly relaxes, thereby keeping the features of a long-tail type time-response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Rodent models of congenital and hereditary cataract in man.

    Science.gov (United States)

    Tripathi, B J; Tripathi, R C; Borisuth, N S; Dhaliwal, R; Dhaliwal, D

    1991-01-01

    Because the organogenesis and physiology of the lens are essentially similar in various mammals, an understanding of the etiology and pathogenesis of the formation of cataract in an animal model will enhance our knowledge of cataractogenesis in man. In this review, we summarize the background, etiology, and pathogenesis of cataracts that occur in rodents. The main advantages of using rodent mutants include the well-researched genetics of the animals and the comparative ease of breeding of large litters. Numerous rodent models of congenital and hereditary cataracts have been studied extensively. In mice, the models include the Cts strain, Fraser mouse, lens opacity gene (Lop) strain, Lop-2 and Lop-3 strains, Philly mouse, Nakano mouse, Nop strain, Deer mouse, Emory mouse, Swiss Webster strain, Balb/c-nct/nct mouse, and SAM-R/3 strain. The rat models include BUdR, ICR, Sprague-Dawley, and Wistar rats, the spontaneously hypertensive rat (SHR), the John Rapp inbred strain of Dahl salt-sensitive rat, as well as WBN/Kob, Royal College of Surgeons (RCS), and Brown-Norway rats. Other proposed models for the study of hereditary cataract include the degu and the guinea pig. Because of the ease of making clinical observations in vivo and the subsequent availability of the intact lens for laboratory analyses at different stages of cataract formation, these animals provide excellent models for clinicopathologic correlations, for monitoring of the natural history of the aging process and of metabolic defects, as well as for investigations on the effect of cataract-modulating agents and drugs, including the prospect of gene therapy.

  7. The investigation on hereditary disease and congenital malformation in the surrounding area of the nuclear test site in Xinjiang

    International Nuclear Information System (INIS)

    Zou Wenliang; Zhang Jujing

    1989-01-01

    The investigation on hereditary disease and congenital malformation, on the children below eleven years old and living in the surrounding area of the nuclear test site and control area is reported. The total prevalence rate of the ninteen kinds of hereditary disease and congenital malformation in both areas are 7.12%0 and 7.28%0, respectively. The prevalence rate of congenital foolishness in investigation area is 0.64%0; while in control area, it is 0.54%0. There is no significant difference between the two areas. However, it is found that the prevalence rate of harelip in investigation area is higher than in control area, whereas the prevalence rate of congenital heart disease in control area is higher than in investigation area. As for the rests there is no significant difference. There is no significant difference between the two areas. It is concluded that nuclear tests in China did not cause hereditary disease and congenital malformation for the children who live in surrounding area, of the nuclear test site

  8. Hereditary Factors Involved in Radiation-Induced Leukaemogenesis

    International Nuclear Information System (INIS)

    Duplan, J.F.

    1969-01-01

    The hereditary factors involved in radiation-induced leukaemogenesis were studied in pure AKR and C57BL strains, their first-generation hybrids and their back-crosses. It is known that the heredity of spontaneous lymphoid leukaemias is attributable to hereditary factors, of which only some are chromosomal, and the same situation can be considered to exist as regards the heredity of radiation-induced leukoses. In order to identify the various chromosomal and non-chromosomal factors concerned, three types of experiment were conducted with the pure strains and with each of the crosses, intended to evaluate (a) the incidence of spontaneous lymphoid leukoses, (b) the incidence of radiation-induced leukoses and (c) the inhibition of radioleukaemo- genesis by the injection of isogenic haematopoietic cells. The results show that the main non-chromosomal factor is the leukaemogenic Gross virus (VG) in the case of the AKR strain and the radioleukaemia virus (VRL) in that of the C57BL strain; these two agents are transmitted by the mother to her progeny. The VG may be responsible for radioleukaemias as well as for spontaneous leukoses, but the VRL does not produce spontaneous leukaemias even in back-crosses possessing a substantial fraction of the AKR genome, which is particularly conducive to leukaemogenesis. Restoration using C57BL bone marrow brings about a distinct inhibition of leukaemogenesis in all animals deriving from crossings for which this material is histocompatible; AKR marrow, however, never exhibits any restorative activity. Three hypotheses may be put forward to explain these results. The first is that C57BL bone marrow contains many more precursor elements than AKR marrow, these cells being necessary for inhibition of the leukaemogenic process. The second hypothesis is that the AKR strain lacks a factor which is essential for the utilization of these precursors. Finally the third hypothesis, which seems the least probable, is that AKR cells are much more

  9. [Review of the recent literature on hereditary neuropathies].

    Science.gov (United States)

    Birouk, N

    2014-12-01

    The recent literature included interesting reports on the pathogenic mechanisms of hereditary neuropathies. The axonal traffic and its abnormalities in some forms of Charcot-Marie-Tooth (CMT) disease were particularly reviewed by Bucci et al. Many genes related to CMT disease code for proteins that are involved directly or not in intracellular traffic. KIF1B controls vesicle motility on microtubules. MTMR2, MTMR13 and FIG4 regulate the metabolism of phosphoinositide at the level of endosomes. The HSPs are involved in the proteasomal degradation. GDAP1 and MFN2 regulate the mitochondrial fission and fusion respectively and the mitochondial transport within the axon. Pareyson et al. reported a review on peripheral neuropathies in mitochondrial disorders. They used the term of "mitochondrial CMT" for the forms of CMT with abnormal mitochondrial dynamic or structure. Among the new entities, we can draw the attention to a proximal form of hereditary motor and sensory neuropathy with autosomal dominant inheritance, which is characterized by motor deficit with cramps and fasciculations predominating in proximal muscles. Distal sensory deficit can be present. The gene TFG on chromosome 3 has been recently identified to be responsible for this form. Another rare form of axonal autosomal recessive neuropathy due to HNT1 gene mutation is characterized by the presence of hands myotonia that appears later than neuropathy but constitute an interesting clinical hallmark to orientate the diagnosis of this form. In terms of differential diagnosis, CMT4J due to FIG4 mutation can present with a rapidly progressive and asymmetric weakness that resembles CIDP. Bouhy et al. made an interesting review on the therapeutic trials, animal models and the future therapeutic strategies to be developed in CMT disease. Copyright © 2014. Published by Elsevier Masson SAS.

  10. Hereditary angioedema: what the gastroenterologist needs to know

    Directory of Open Access Journals (Sweden)

    Ali MA

    2014-11-01

    Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis

  11. Kindler syndrome - a rare type of hereditary epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    V. I. Albanova

    2015-01-01

    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.

  12. Hereditary neuropathy with liability to pressure palsy: a brief review with a case report.

    Science.gov (United States)

    Rana, Abdul Qayyum; Masroor, Mohamed Sufian

    2012-03-01

    Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is an autosomal dominant disorder and is usually characterized by episodes of recurrent and painless focal motor and sensory peripheral mononeuropathy. This condition is usually localized around areas of entrapment (predominantly the wrists, knees, elbows, and shoulders). The genetic locus of the disease is chromosome 17p12. A deletion of the PMP22 gene results in the lack of peripheral myelin protein, a key component to the myelin sheet of peripheral nerves. However, this disease may be completely asymptomatic until an event, such as a minor trauma, triggers these episodes, as seen in our presented case report. The diagnosis of HNPP can be somewhat challenging, as other diseases, such as Charcot-Marie-Tooth disease type 1A (CMT) and Hereditary Neuralgic Amyotrophy (HNA) must be included in the differential diagnosis due to their overlapping clinical features. There are currently no treatments to cure the disease, but therapies seek to alleviate the symptoms and recurring episodes.

  13. The contribution of self-esteem and self-concept in psychological distress in women at risk of hereditary breast cancer.

    Science.gov (United States)

    den Heijer, Mariska; Seynaeve, Caroline; Vanheusden, Kathleen; Duivenvoorden, Hugo J; Vos, Joël; Bartels, Carina C M; Menke-Pluymers, Marian B E; Tibben, Aad

    2011-11-01

    Clarification of the role of several aspects of self-concept regarding psychological distress in women at risk of hereditary breast cancer will help to target counselling and psychosocial interventions more appropriately. In this study, we aimed (1) to examine the role of general self-esteem and specific aspects of self-concept (i.e. stigma, vulnerability, and mastery) in psychological distress in women at risk of hereditary breast cancer and (2) to compare the relative importance of these self-concept aspects in psychological distress in women with low versus high self-esteem. General and breast-cancer-specific distress, self-esteem, self-concept, and demographics were assessed in 246 women being at risk of hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. In the total study group, self-esteem was negatively associated with general distress. Furthermore, feeling stigmatized was strongly associated with more breast-cancer-specific distress, and to a lesser degree with general distress. In women with low-self esteem, feelings of stigmatization were strongly associated with higher levels of both breast-cancer-specific and general distress, while a sense of mastery was associated with less general distress. For women with high self-esteem, feelings of both stigmatization and vulnerability were associated with more breast-cancer-specific distress, whereas there were no significant associations with general distress. Psychosocial interventions or support groups for women at risk of hereditary breast cancer should focus on self-esteem and feelings of stigmatization and isolation, and consequently tailor the interventions on specific items for respective women. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Mitochondrial DNA analysis as a diagnostic tool in singleton cases of Leber's hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, R. J.; Bolhuis, P. A.; Bleeker-Wagemakers, E. M.

    1993-01-01

    Leber's hereditary optic neuropathy (LHON) is characterized by subacute loss of central vision due to bilateral optic nerve atrophy accompanied by several nonspecific clinical findings. The only pathognomonic feature is its strictly maternal inheritance. It was therefore impossible to establish the

  15. Radiographic diagnosis of hereditary chondrodysplasia in newborn lambs

    International Nuclear Information System (INIS)

    Vanek, J.A.; Walter, P.A.; Alstad, A.D.

    1989-01-01

    Normal appearing Suffolk lambs affected with hereditary chondrodysplasia (HC) and normal appearing unaffected lambs were radiographed at birth, and at 2, 4, and 8 weeks of age. In affected lambs, lesions were seen consistently in the elbows, shoulders, sternum, and spine. Similar lesions were not identified in unaffected lambs. A malformed Corriedale lamb was radiographed to compare its lesions to those seen in HC. The Corriedale lamb had islands of ossification of the anconeal process similar to those identified in lambs with signs of HC at birth. The islands of ossification seen in the Corriedale lamb were fused by 2 months of age, whereas elbow lesions seen in lambs with HC increased in severity during the same period

  16. Radiobiology in clinical radiation therapy - Part IV: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

    International Nuclear Information System (INIS)

    Brenner, David J.

    1996-01-01

    The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

  17. 76 FR 73691 - Oral Argument

    Science.gov (United States)

    2011-11-29

    ...-1; and Marcella Albright v. U.S. Postal Service, MSPB Docket Number DC-0752- 11-0196-I-1. Date and... Docket Number AT-0353-11-0369-I-1; and Marcella Albright v. U.S. Postal Service, MSPB Docket Number DC...

  18. Aplastic crisis in occult hereditary spherocytosis caused by human parvovirus (HPV B19).

    Science.gov (United States)

    Rappaport, E S; Quick, G; Ransom, D; Helbert, B; Frankel, L S

    1989-02-01

    We have reported a case of aplastic crisis occurring in an 11-year-old black boy with occult hereditary spherocytosis. An etiologic diagnosis of human parvovirus (HPV) B19 infection was confirmed serologically. The Coulter Model S + IV proved useful for both diagnosis and treatment monitoring through serial histograms. The relationship of HPV infection and aplastic crisis is discussed.

  19. Identification of a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population by next-generation sequencing.

    Directory of Open Access Journals (Sweden)

    Xiaochen Yang

    Full Text Available The genetic etiology of hereditary breast cancer has not been fully elucidated. Although germline mutations of high-penetrance genes such as BRCA1/2 are implicated in development of hereditary breast cancers, at least half of all breast cancer families are not linked to these genes. To identify a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population, we performed an analysis of germline mutations in 2,165 coding exons of 152 genes associated with hereditary cancer using next-generation sequencing (NGS in 99 breast cancer patients from families of cancer patients regardless of cancer types. Forty-two deleterious germline mutations were identified in 21 genes of 34 patients, including 18 (18.2% BRCA1 or BRCA2 mutations, 3 (3% TP53 mutations, 5 (5.1% DNA mismatch repair gene mutations, 1 (1% CDH1 mutation, 6 (6.1% Fanconi anemia pathway gene mutations, and 9 (9.1% mutations in other genes. Of seven patients who carried mutations in more than one gene, 4 were BRCA1/2 mutation carriers, and their average onset age was much younger than patients with only BRCA1/2 mutations. Almost all identified high-penetrance gene mutations in those families fulfill the typical phenotypes of hereditary cancer syndromes listed in the National Comprehensive Cancer Network (NCCN guidelines, except two TP53 and three mismatch repair gene mutations. Furthermore, functional studies of MSH3 germline mutations confirmed the association between MSH3 mutation and tumorigenesis, and segregation analysis suggested antagonism between BRCA1 and MSH3. We also identified a lot of low-penetrance gene mutations. Although the clinical significance of those newly identified low-penetrance gene mutations has not been fully appreciated yet, these new findings do provide valuable epidemiological information for the future studies. Together, these findings highlight the importance of genetic testing based on NCCN guidelines and a multi-gene analysis

  20. N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom

    NARCIS (Netherlands)

    Kalaydjieva, L.; Gresham, D.; Gooding, R.; Heather, L.; Baas, F.; de Jonge, R.; Blechschmidt, K.; Angelicheva, D.; Chandler, D.; Worsley, P.; Rosenthal, A.; King, R. H.; Thomas, P. K.

    2000-01-01

    Hereditary motor and sensory neuropathies, to which Charcot-Marie-Tooth (CMT) disease belongs, are a common cause of disability in adulthood. Growing awareness that axonal loss, rather than demyelination per se, is responsible for the neurological deficit in demyelinating CMT disease has focused

  1. Informing family members about a hereditary predisposition to cancer: attitudes and practices among clinical geneticists

    NARCIS (Netherlands)

    Stol, Y.; Menko, F.H.; Westerman, M.J.; Janssens, M.J.P.A.

    2010-01-01

    If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic

  2. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis)

    OpenAIRE

    Kantanen, Mari; Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

    2014-01-01

    Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuro...

  3. Autosomal recessive type II hereditary motor and sensory neuropathy with acrodystrophy.

    Science.gov (United States)

    Thomas, P K; Claus, D; King, R H

    1999-02-01

    A family is described with presumed autosomal recessive inheritance in which three siblings developed a progressive neuropathy that combined limb weakness and severe distal sensory loss leading to prominent mutilating changes. Electrophysiological and nerve biopsy findings indicated an axonopathy. The disorder is therefore classifiable as type II hereditary motor and sensory neuropathy (HMSN II). The clinical features differ from those reported in previously described cases of autosomal recessive HMSN II. This disorder may therefore represent a new variant.

  4. Interdisciplinary management for restoration of function and esthetics in a patient with hereditary amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Sushma Dhiman

    2015-01-01

    Full Text Available Amelogenesis imperfecta (AI is a type of the hereditary disorder which is expressed as a group of conditions causing developmental alterations in the structure of enamel. It is associated with a reduction of oral health-related quality-of-life, has an impact on psychological well-being, and leads to various physiological problems. Children or adults with AI express varying degree of malocclusions either in the form of crowding, impacted teeth, spacing, retained teeth, reduced vertical height due to abnormal tooth structure or undue tooth loss. Orthodontic treatment should precede esthetic rehabilitation. Proper diagnosis of the case is quintessential to provide durable functional and esthetic result to these patients, improving the quality of their lives. We present a case of interdisciplinary management for restoring function and esthetics in a patient with hereditary AI of the hypoplastic type accompanied with tooth impaction and some other dental anomalies.

  5. Effect of epithalon on age-specific changes in the retina in rats with hereditary pigmentary dystrophy.

    Science.gov (United States)

    Khavinson, V Kh; Razumovskii, M I; Trofimova, S V; Grigor'yan, R A; Chaban, T V; Oleinik, T L; Razumovskaya, A M

    2002-01-01

    The effect of peptide bioregulator Epithalon on the course of hereditary pigmentary retinal degeneration was studied in Campbell rats. Administration of epithalon starting from birth protected morphological structure, increased its bioelectrical activity, and improved its function.

  6. Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Erik; Johnson, B; Koefoed, Pernille

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  7. Hereditary sensory and autonomic neuropathy type IV and orthopaedic complications.

    Science.gov (United States)

    Kim, W; Guinot, A; Marleix, S; Chapuis, M; Fraisse, B; Violas, P

    2013-11-01

    Hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is a very rare autosomal recessive disorder characterized by recurrent episodes of unexplained fever, extensive anhidrosis, total insensitivity to pain, hypotonia, and mental retardation. The most frequent complications of this disease are corneal scarring, multiple fractures, joint deformities, osteomyelitis, and disabling self-mutilations. We reported the case of a 12-year-old boy. The goal was to discuss our decision-making and compare this case with cases described in the literature. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Efficiency of laser treatment in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Jørgensen, Gita; Lange, Bibi; Wanscher, Jens Højberg

    2011-01-01

    Earlier studies have shown the effect of laser treatment on epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). At the present time, only very few prospective trials have been performed, and many studies are based on patients' subjective assessment of the severity of epistaxis....... This prospective study measures the objective effect of laser treatment in HHT patients with mild to moderate epistaxis. We introduce an objective measure to assess the severity of epistaxis: the bleeding time (BT). Before and after treatment, the quality of life, as measured by the patient, was assessed...

  9. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  10. Developing an item bank to measure the coping strategies of people with hereditary retinal diseases.

    Science.gov (United States)

    Prem Senthil, Mallika; Khadka, Jyoti; De Roach, John; Lamey, Tina; McLaren, Terri; Campbell, Isabella; Fenwick, Eva K; Lamoureux, Ecosse L; Pesudovs, Konrad

    2018-05-05

    Our understanding of the coping strategies used by people with visual impairment to manage stress related to visual loss is limited. This study aims to develop a sophisticated coping instrument in the form of an item bank implemented via Computerised adaptive testing (CAT) for hereditary retinal diseases. Items on coping were extracted from qualitative interviews with patients which were supplemented by items from a literature review. A systematic multi-stage process of item refinement was carried out followed by expert panel discussion and cognitive interviews. The final coping item bank had 30 items. Rasch analysis was used to assess the psychometric properties. A CAT simulation was carried out to estimate an average number of items required to gain precise measurement of hereditary retinal disease-related coping. One hundred eighty-nine participants answered the coping item bank (median age = 58 years). The coping scale demonstrated good precision and targeting. The standardised residual loadings for items revealed six items grouped together. Removal of the six items reduced the precision of the main coping scale and worsened the variance explained by the measure. Therefore, the six items were retained within the main scale. Our CAT simulation indicated that, on average, less than 10 items are required to gain a precise measurement of coping. This is the first study to develop a psychometrically robust coping instrument for hereditary retinal diseases. CAT simulation indicated that on an average, only four and nine items were required to gain measurement at moderate and high precision, respectively.

  11. The Hereditary Hyperferritinemia-Cataract Syndrome in 2 Italian Families

    Directory of Open Access Journals (Sweden)

    Katia Perruccio

    2013-01-01

    Full Text Available Two 8- and 9-year-old brothers were referred to the Pediatric Oncology Unit, Perugia General Hospital, because of hyperferritinemia. Both had a history of bilateral cataract and epilepsy. Genetic investigation revealed two distinct mutations in iron haemostasis genes; homozygosity for the HFE gene H63D mutation in the younger and heterozygosity in the elder. Both displayed heterozygosity for C33T mutation in the ferritin light chain iron response element. A 7-year-old boy from another family was referred to our unit because of hyperferritinemia. Genetic analyses did not reveal HFE gene mutations. Family history showed that his mother was also affected by hyperferritinemia without HFE gene mutations. Magnetic resonance imaging in the mother was positive for iron overload in the spleen. Cataract was diagnosed in mother and child. Further genetic investigation revealed the C29G mutation of the ferritin light chain iron response element. C33T and C29G mutations in the ferritin light chain iron response element underlie the Hereditary Hyperferritinemia-Cataract Syndrome (HHCS. The HFE gene H63D mutation underlies Hereditary Haemochromatosis (HH, which needs treatment to prevent organ damages by iron overload. HHCS was definitively diagnosed in all three children. HHCS is an autosomal dominant disease characterized by increased L-ferritin production. L-Ferritin aggregates accumulate preferentially in the lens, provoking bilateral cataract since childhood, as unique known organ damage. Epilepsy in one case and the spleen iron overload in another could suggest the misleading diagnosis of HH. Consequently, the differential diagnosis between alterations of iron storage system was essential, particularly in children, and required further genetic investigation.

  12. The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Gerdes, Anne-Marie; Mosgaard, Berit

    2014-01-01

    Objective. We aimed to estimate the incidence rate of endometrial cancer (EC) and to evaluate the results of EC-surveillance in hereditary nonpolyposis colorectal cancer (HNPCC) families. Methods. All at-risk women recommended for EC-surveillance by the HNPCC-register-2959 women (19,334 women yea...... of having Lynch syndrome. We conclude that EC surveillance should only be targeted at MMR-mutation carriers. (C) 2014 Elsevier Inc. All rights reserved....

  13. Neurologic Manifestation as Initial Presentation in a Case of Hereditary Haemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Yeow Kwan Teo

    2010-01-01

    Full Text Available Hereditary Haemorrhagic Telangiectasia (HHT, or Osler-Weber-Rendu syndrome is an uncommon autosomal dominant multi-organ condition of vascular dysplasias. We describe a 19 year old Indian female who presented with cerebral abscess secondary to paradoxical emboli from pulmonary arteriovenous malformations (PAVMs associated with HHT. Cerebral, pulmonary, hepatic and gastrointestinal involvement can be life-threatening and it is important to have lifelong follow-ups on these patients.

  14. Radiological features of bilateral hereditary micro-epiphyseal dysplasia - a distinct entity in the skeletal dysplasias

    NARCIS (Netherlands)

    Morstert, AK; Dijkstra, PF; van Horn, [No Value; Jansen, BRH; Heutink, P; Lindhout, D

    Aim: To prove that bilateral hereditary micro-epiphyseal dysplasia (BHMED), first described by Elsbach in 1959 [1], is a distinct disorder radiologically as well as clinically, compared with multiple epiphyseal dysplasia (MED). Material and Methods: We used the data of the revised pedigree with 84

  15. Mania associated with complicated hereditary spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Raghavendra B Nayak

    2011-01-01

    Full Text Available Hereditary spastic paraparesis (HSP is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient′s father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  16. Mania associated with complicated hereditary spastic paraparesis.

    Science.gov (United States)

    Nayak, Raghavendra B; Bhogale, Govind S; Patil, Nanasaheb M; Pandurangi, Aditya A

    2011-07-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient's father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  17. Prosthodontic Rehabilitation of Hereditary Ectodermal Dysplasia in an 11-Year-Old Patient with Flexible Denture: A Case Report

    Directory of Open Access Journals (Sweden)

    Neha Jain

    2012-01-01

    Full Text Available Hereditary ectodermal dysplasia is a rare group of inherited disorders characterized by aplasia or dysplasia of two or more tissues of ectodermal origin such as hair, nails, teeth, and skin. The dental characteristics of this syndrome include anodontia or hypodontia of the primary and/or permanent teeth, hypoplastic conical teeth, and underdevelopment of the alveolar ridges. The options for a definitive treatment plan include fixed, removable or implant-supported prostheses, singly or in combination. This clinical report describes the prosthetic rehabilitation of an 11-year-old boy with hereditary ectodermal dysplasia. Maxillary flexible removable partial denture and mandibular conventional complete denture were fabricated to establish an acceptable masticatory function, speech, and esthetics for the patient.

  18. [Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses].

    Science.gov (United States)

    Cammarata-Scalisi, Francisco; Cozar, Mónica; Grinberg, Daniel; Balcells, Susana; Asteggiano, Carla G; Martínez-Domenech, Gustavo; Bracho, Ana; Sánchez, Yanira; Stock, Frances; Delgado-Luengo, Wilmer; Zara-Chirinos, Carmen; Chacín, José Antonio

    2015-04-01

    Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18,000 to 1/50,000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses.

  19. The role of Clinical Geneticists in Hereditary Cancer Management and Research

    Directory of Open Access Journals (Sweden)

    Hanne Meijers Heijboer

    2017-02-01

    Full Text Available Abstract Hereditary cancer refers to cancers caused by germline mutations in cancer predisposing genes. These mutations confer a significantly increased risk of cancer, are rare, and are in the majority of cases autosomal dominantly inherited.  Since the eighties of last century more than 115 cancer predisposing genes have been identified. In many Western countries genetic testing of patients and families with clustering of cancers started early, and was often performed by clinical geneticists (MDs performed the counselling and pedigree analyses and by molecular biologists (in laboratories within departments of clinical genetics.  It turned out to be a long path to fully realize the promise of cancer predisposing genes. The clinical utility of many cancer genetic tests and subsequent risk reducing interventions has not yet been validated and pitfalls in e.g. misinterpretation of genetic variants showed up. However, without doubt genetic testing for mutations will eventually turn out as a strong tool to save lives from early cancer death and will become part of standard cancer care throughout the developed world.  Apart from primary surgical prevention, major progress is to be expected in earlier diagnoses, tailored therapies, and possibly chemoprevention.  Ideally researchers, clinical geneticists, molecular biologists, surgeons, oncologists, gynaecologists and other professionals will work together to reach this goal. Keywords : clinical genetics, germline, hereditary cancers, cancer predisposing genes

  20. Follow-up of Thalidomide treatment in patients with Hereditary Haemorrhagic Telangiectasia.

    Science.gov (United States)

    Hosman, A; Westermann, C J J; Snijder, R; Disch, F; Mummery, C L; Mager, J J

    2015-12-01

    Patients with a hereditary vascular disorder called Rendu-Osler-Weber syndrome (Hereditary Haemorrhagic Telangiectasia, HHT) haemorrhage easily due to weak-walled vessels. Haemorrhage in lungs or brain can be fatal but patients suffer most from chronic and prolonged nosebleeds (epistaxis), the frequency and intensity of which increases with age. Several years ago, it was discovered serendipitously that the drug Thalidomide had beneficial effects on the disease symptoms in several of a small group of HHT patients: epistaxis and the incidence of anaemia were reduced and patients required fewer blood transfusions. In addition, they reported a better quality of life. However, Thalidomide has significant negative side effects, including neuropathy and fatigue. We followed up all HHT patients in the Netherlands who had been taking Thalidomide at the time the original study was completed to find out (i) how many had continued taking Thalidomide and for how long (ii) the nature and severity of any side-effects and (iii) whether side-effects had influenced their decision to continue taking Thalidomide. Only a minority of patients had continued taking the drug despite its beneficial effects on their symptoms and that the side effects were the primary reason to stop. Despite symptom reduction, alternative treatments are still necessary for epistaxis in HHT patients and a large-scale clinical trial is not justified although incidental use in the most severely affected patients can be considered.

  1. A Topic Diathesis In Hereditary Ichthyosis Patients Attending A Tertiary Health Care Center In Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Al-Akloby Omar M Al-Amro

    2004-01-01

    Full Text Available The occurrence of atopic diathesis in hereditary ichthyosis (HI has not been documented in Saudi patients. The atopic manifestations in histopathologically confirmed HI patients attending the dermatology clinic of king Fahad Hospital of the University at Al-Khobar city, Saudi Arabia is discussed in this study. From the dermatology OPD logbook, all Saudi patients with confirmed HI seen between January 1990 to December 1995 were included in the study. The findings regarding atopic manifestations were extracted into data collection forms and analyzed. During the 5 year study period, 10,455 new cases were seen in our dermatology OPD. Of these, 61 had hereditary icthyosis, with 37 males and 24 females with a male to female ratio of 1.5:1. Thus, the frequency of HI among Saudi hospital attendees was 6 per 1000 new cases. The type of HI was ichthyosis vulgaris in 25 (41% patients, X-linked recessive ichthyosis in 11 (18%, lamellar ichthyosis in 4(7%, bullous ichthyosiform erythroderma in 2 (3% and nonbullous ichthyosiform erythroderma was seen in 19 (31%. Generalized pruritus was present in 49 (80% cases, atopic dermatitis in , elevated serum IgE level was noted in 27 and bronchial asthma in 3 cases. Dandruff was reported in 24 cases, keratosis pilaris in15, recurrent skin infection in 7. Combination of hereditary ichthyosis, generalized pruritus and high serum IGE level was reported in 27 (44.3% patient.

  2. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2008-09-15

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT.

  3. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    International Nuclear Information System (INIS)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin

    2008-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT

  4. Hereditary spastic paraplegias: membrane traffic and the motor pathway.

    Science.gov (United States)

    Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

    2011-01-01

    Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

  5. Bilateral vision loss due to Leber's hereditary optic neuropathy after long-term alcohol, nicotine and drug abuse.

    Science.gov (United States)

    Maass, Johanna; Matthé, Egbert

    2018-04-01

    Leber's hereditary optic neuropathy is relatively rare, and no clinical pathognomonic signs exist. We present a rare case of bilateral vision loss of a patient with multiple drug abuse in the history. A 31-year-old man presented with a history of progressive, decreased vision in both eyes for 6 month. On examination, his visual acuity was hand motion in both eyes. Funduscopy demonstrated a temporal pallor of the optic disc. Goldmann visual field perimetry showed a crescent visual field in the right eye and a circular decrease to less than 50 ° in the left eye. Electroretinogram showed a scotopic b-wave amplitude reduction. Optical coherence tomographies, Heidelberg Retina tomography, visual evoked potentials, and magnetic resonance imaging with contrast as well as blood tests were normal. The patient reported to consume various kinds of drugs as well as recreational drug use and alcohol consumption since he was 16 years old. We started a hemodilution therapy, believing the patient suffered from a bilateral, toxic optic neuropathy due to his lifestyle. Laboratory results later on showed Leber's hereditary optic neuropathy. Leber's hereditary optic neuropathy is a rare disease without a typical, pathognomonic presentation. Even though the patient gave good reasons for a toxic optic neuropathy, one should never stop to test for other diseases.

  6. Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I.

    Science.gov (United States)

    Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R; Janecke, Andreas R; Blackstone, Craig; Auer-Grumbach, Michaela

    2011-01-07

    Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders.

  7. Socioeconomic burden of hereditary angioedema: results from the hereditary angioedema burden of illness study in Europe.

    Science.gov (United States)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B; Caballero, Teresa

    2014-07-04

    Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the patient perspective in Europe. The study was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE via a cross-sectional survey of HAE patients, including direct and indirect resource utilization during and between attacks for patients and their caregivers over the past 6 months. A regression model examined predictors of medical resource utilization. Overall, 164 patients had an attack in the past 6 months and were included in the analysis. The most significant predictor of medical resource utilization was the severity of the last attack (OR 2.6; p career/educational advancement. HAE poses a considerable burden on patients and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks.

  8. Leber hereditary optic neuropathy due to a new ND1 mutation

    DEFF Research Database (Denmark)

    Soldath, Patrick; Wegener, Marianne; Sander, Birgit

    2017-01-01

    We report a proband with Leber hereditary optic neuropathy (LHON), in whom we have identified a novel homoplasmic m.3,395A>G mutation in the ND1 gene. The mutation alters a highly conserved amino acid in codon 30 which previously has been associated with LHON and leads to a severe selective complex...... and is present in the early stage of the disease. Furthermore, evaluation of two unaffected mutation carriers disclosed asymptomatic borderline ganglion cell loss and thin pRNFL in one....

  9. Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Pawel Domagala

    Full Text Available This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs and to poly(ADP-ribose polymerase (PARP inhibitors.Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Thirty five (22.2% of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7% of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%, and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%. In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined were identified in the hereditary non-triple-negative group.Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

  10. Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight

    DEFF Research Database (Denmark)

    Caballero, Teresa; Zanichelli, Andrea; Aberer, Werner

    2018-01-01

    Background: Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in ...

  11. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant

    DEFF Research Database (Denmark)

    Aberer, Werner; Maurer, Marcus; Bouillet, Laurence

    2017-01-01

    BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prop...

  12. Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care

    Directory of Open Access Journals (Sweden)

    Palmero Edenir I

    2009-08-01

    Full Text Available Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2 had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65. Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at

  13. Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome

    DEFF Research Database (Denmark)

    Nielsen, J.E.; Jensen, L. Neerup; Krabbe, K.

    1995-01-01

    . A patient is reported with hereditary haemochromatosis and a syndrome of dementia, dysarthria, a slowly progressive gait disturbance, imbalance, muscle weakness, rigidity, bradykinesia, tremor, ataxia, and dyssynergia. The findings on MRI of a large signal decrease in the basal ganglia, consistent...

  14. [Evaluation of fundus autofluorescence in hereditary retinal diseases using Heidelberg Retina Angiograph2].

    Science.gov (United States)

    Côco, Monique; Baba, Natalia Tamie; Sallum, Juliana Maria Ferraz

    2007-01-01

    To define characteristics of the fundus autofluorescence examination, verifying usefulness in the diagnosis and care of hereditary retinal diseases. 28 patients, adults, divided equally into four groups with diagnoses of Stargardt macular dystrophy, cone dystrophy, retinitis pigmentosa and healthy volunteers for the establishment of the normality pattern. An average of nine images with the filter for fluorescein angiography was obtained for the formation of the image autofluorescence using Heidelberg Retina Angiograph2. The images of each group of patients were analyzed to verify common characteristics. The fundus autofluorescence of healthy volunteers showed the foveal area darker than the surrounding retina. The images of Stargardt macular dystrophy, in general, presented an oval central lesion, with reduced autofluorescence. The main alterations of the autofluorescence in patients with cone dystrophy were reduced foveal autofluorescence with a parafoveal ring of increased autofluorescence. In general, the images of retinitis pigmentosa showed outlying pigments with reduced autofluorescence, and of the foveal area, in some cases disorganization or reduced autofluorescence. The study showed the existence of patterns of fundus autofluorescence in the hereditary retinal diseases that allow the diagnosis and better interpretation of the pathogenesis of these diseases.

  15. Hereditary Spherocytosis Unmasked by Human Parvovirus B19 Induced Aplastic Crisis in a Family

    Directory of Open Access Journals (Sweden)

    Samin Alavi

    2015-09-01

    Full Text Available Human parvovirus (HPV B19 induced aplastic crisis in a family leading to the diagnosis of hereditary spherocytosis (HS is a very rare condition being barely reported in the literature. We herein report a 4-year-old girl, her brother, and their mother who all presented with progressive pallor and jaundice after a febrile illness. The HPV B19 was diagnosed using polymerase chain reaction (PCR and positive serology for specific anti-HPV B19 IgM. They were further diagnosed with having HS. The clinical importance of this report is that in the case of an abrupt onset of unexplained severe anemia and jaundice, one should consider underlying hemolytic anemias mostly hereditary spherocytosis complicated by HPV B19 aplastic crisis. Herein, we report the occurrence of this condition, simultaneously in three members of a family. The distinguished feature of this report is that all affected family members developed some degrees of transient pancytopenia, not only anemia, all simultaneously in the course of their disease.

  16. Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

    OpenAIRE

    Hilary Longhurst

    2018-01-01

    Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophyla...

  17. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    International Nuclear Information System (INIS)

    Loefberg, M.; Liewendahl, K.; Savolainen, S.; Nikkinen, P.; Lamminen, A.; Tiula, E.; Somer, H.

    1994-01-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  18. Accessory mammary tissue associated with congenital and hereditary nephrourinary malformations.

    Science.gov (United States)

    Urbani, C E; Betti, R

    1996-05-01

    The association between polythelia (supernumerary nipple) and kidney and urinary tract malformations (KUTM) is controversial. Some authors reported this association in newborns and infants. Case-control studies dealing with adult subjects are not found in the literature. The purpose of this study is to determine the frequency of the association between accessory mammary tissue (AMT) and congenital and hereditary nephrourinary defects in an adult population compared to a control group. The study was performed in 146 white patients (123 men, 23 women) with AMT out of 2645 subjects consecutively referred to us for physical examination. The following investigations were undertaken: ultrasonographic examination of the abdomen and the kidneys, ECG, echocardiogram, roentgenogram of the vertebral column, urinalysis, and other laboratory tests. A sex- and age-matched control group without any evidence of AMT or lateral displacement of the nipples underwent the same examinations. Kidney and urinary tract malformations were detected in 11 patients with AMT (nine men, two women) and in one control. These data indicate a significantly higher frequency of KUTM in the AMT-affected patients compared to controls (7.53% vs. 0.68%, P < 0.001). A broad spectrum of KUTM was discovered in association with AMT: adult dominant polycystic kidney disease, unilateral renal agenesis, cystic renal dysplasia, familial renal cysts, and congenital stenosis of the pyeloureteral joint. Accessory mammary tissue offers an important clue for congenital and hereditary anomalies of the kidneys and urinary collecting systems. Patients with AMT should, therefore, be extensively examined for the presence of occult nephrouropathies.

  19. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Loefberg, M. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland)); Liewendahl, K. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Savolainen, S. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Nikkinen, P. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Lamminen, A. (Dept. of Radiology, Helsinki Univ. Central Hospital (Finland)); Tiula, E. (First Dept. of Internal Medicine, Helsinki Univ. Central Hospital (Finland)); Somer, H. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland))

    1994-10-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  20. Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets

    Science.gov (United States)

    Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolis...

  1. Specific Radiological Imaging Findings in Patients With Hereditary Pancreatitis During a Long Follow-up of Disease

    NARCIS (Netherlands)

    Esch, A.A.J. van; Drenth, J.P.H.; Hermans, J.J.

    2017-01-01

    OBJECTIVES: Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP. METHODS: We retrospectively collected data

  2. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)

    DEFF Research Database (Denmark)

    Shovlin, C L; Guttmacher, A E; Buscarini, E

    2000-01-01

    Hereditary Hemorrhagic Telangiectasia (HHT) is easily recognized in individuals displaying the classical triad of epistaxis, telangiectasia, and a suitable family history, but the disease is more difficult to diagnosis in many patients. Serious consequences may result if visceral arteriovenous ma...... in this disorder. These criteria may be refined as molecular diagnostic tests become available in the next few years....... of the HHT Foundation International, Inc., we present consensus clinical diagnostic criteria. The four criteria (epistaxes, telangiectasia, visceral lesions and an appropriate family history) are carefully delineated. The HHT diagnosis is definite if three criteria are present. A diagnosis of HHT cannot...

  3. In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA-damaging agents

    International Nuclear Information System (INIS)

    Woods, W.G.; Byrne, T.D.

    1986-01-01

    We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA-damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strains derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents

  4. Atrofia óptica hereditaria autosómica dominante: A propósito de una familia Dominant autosomal hereditary optical atrophy: Apropos of a family

    Directory of Open Access Journals (Sweden)

    Noel Taboada Lugo

    2004-12-01

    Full Text Available Entre las causas de pérdida insidiosa, bilateral y simétrica de la visión central se deben tener siempre presente las atrofias ópticas heredo degenerativas. La atrofia óptica hereditaria autosómica dominante es la forma más frecuente de atrofia óptica heredofamiliar simple o monosintomática. Se realizó la caracterización clínica de una familia con el diagnóstico de esta discapacidad visual.Among the causes of insidious, bilateral and symmetric loss of the central vision, the hereditary and degenerative optical atrophies should always be taken into account. The dominant autosomal hereditary optical atrophy is the most frequent form of simple or monosymptomatic hereditary family optical atrophy. The clinical characterization of a family with the diagnosis of this visual impairment was made.

  5. Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.

    Science.gov (United States)

    Lenzhofer, Markus; Schroedl, Falk; Trost, Andrea; Kaser-Eichberger, Alexandra; Wiedemann, Helmut; Strohmaier, Clemens; Hohensinn, Melchior; Strasser, Michael; Muckenthaler, Martina U; Grabner, Guenther; Aigner, Elmar; Reitsamer, Herbert A

    2015-04-01

    Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare autosomal dominant hereditary disease, characterized by hyperferritinemia but with absence of body iron excess and early onset of bilateral cataracts. Although 5- to 20-fold increased serum ferritin concentrations have been reported in HHCS patients, data of ferritin levels in aqueous humor have not been obtained. We therefore aimed to investigate the ferritin levels in aqueous humor and serum and further present histological and ultrastructural data of the lens. During cataract extraction and intraocular lens implantation, aqueous humor and lens aspirate of a 37-year-old HHCS patient were obtained from both eyes. Ferritin levels in serum and aqueous humor were quantitatively analyzed via immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens aspirate in HHCS was analyzed histologically and at the ultrastructural level. Further, genetic mutation screening by polymerase chain reaction and DNA sequencing in blood was performed. Serum ferritin levels in the control group were 142.2 ± 38.7 μg/L, whereas in the HHCS patient, this parameter was excessively increased (1086 μg/L). Analysis of ferritin in aqueous humor revealed 6.4 ± 3.8 μg/L in normal control subjects and 146.3 μg/L (OD) and 160.4 μg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on position +18, a T>G mutation on position +22, a T>C mutation on position +24, and a T>G polymorphism on position +26 in the iron-responsive element of the light-chain ferritin (L-ferritin) gene. In the HHCS patient, a 23-fold (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected. Therefore, the formation of bilateral cataract in HHCS is most likely a result of elevated aqueous humor ferritin. In addition, a novel mutation in this rare disease in the iron-responsive element of L-ferritin gene is reported.

  6. Molecular biology methods in assessing radiation-induced hereditary risks in humans

    International Nuclear Information System (INIS)

    Kiuru, A.

    2004-12-01

    Effort to predict the genetic consequences for humans of exposure to ionising radiation has been one of the most important issues of human genetics over the past 60 years. To date, there has been little experimental knowledge on the genetic risks of human exposure to ionising radiation. Radiation-induced deleterious hereditary effects have not been detected in human populations - not even among the offspring of atomic bomb survivors in Hiroshima and Nagasaki. This does not mean deleterious hereditary effects do not exist in humans, but rather that they are small and/or difficult to detect because the normal incidence of inherited abnormalities is quite high in the human population. Thus, assessment of radiation-induced hereditary risks in humans has been based on the common knowledge of human heredity and on animal experiments. However, recent data have suggested that hyper-variable tandem repeat minisatellite loci provide a useful and sensitive experimental approach for monitoring radiation-induced germline mutations in humans. In order to investigate the feasibility of the minisatellite mutation screening system in assessing radiation-induced hereditary risks in humans, we examined the amount of hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers. The men studied received a median radiation dose of 109 mSv while working on the cleanup activities after the Chernobyl accident. We compared the minisatellite mutation rates of 155 children born to 147 Estonian Chernobyl cleanup workers after the accident to those of their 148 siblings born prior to it. In addition, 44 Estonian families, where the father had not been exposed to radiation, composed an additional control group. In all of these families, the paternity of the children was ascertained by using 5 minisatellite loci (APOB, HRAS, MCOB19, MCT118, and YNZ-22) in PCR-based analyses. Other 8 minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, and MS32) were used

  7. Use of hereditary for the detection of radioinduced variability in the height of tomato plants

    International Nuclear Information System (INIS)

    Fundora, Z.; Perez Talavera, S.; Auchet, F.; Moya, C.

    1986-01-01

    This paper is about the study of induced variability in the height of tomato plants from seeds treated with Co-60 gamma-rays. Hereditary coefficients in narrow sense were used trough progenitor-descendant regression of varieties irradiated on the control as indicator of the variability induced by the different doses

  8. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

    Science.gov (United States)

    Geisthoff, Urban W; Seyfert, Ulrich T; Kübler, Marcus; Bieg, Birgitt; Plinkert, Peter K; König, Jochem

    2014-09-01

    Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Multigeneration family with dominant SPG30 hereditary spastic paraplegia.

    Science.gov (United States)

    Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig

    2017-11-01

    Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.

  10. Hereditary hypertriglyceridemic rat: a suitable model of cardiovascular disease and metabolic syndrome?

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pecháňová, Olga; Čačányiová, S.; Cebová, M.; Kristek, F.; Török, J.; Šimko, F.; Dobešová, Zdenka; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. S1 (2006), S49-S63 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA MZd(CZ) NR7786 Grant - others:VEGA(SK) 2/6148/26; VEGA(SK) 2/6150/26; VEGA(SK) 1/3429/06; VEGA(SK) 2/3139/26 Institutional research plan: CEZ:AV0Z50110509 Keywords : hereditary hypertriglyceridemic rat * insulin resistance * hypertension Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  11. Hereditary thrombophilia and recurrent pregnancy loss: a retrospective cohort study of pregnancy outcome and obstetric complications

    DEFF Research Database (Denmark)

    Lund, Marie; Nielsen, H S; Hviid, T V

    2010-01-01

    The association among hereditary thrombophilia, recurrent pregnancy loss (RPL) and obstetric complications is yet uncertain. The objective of the study was to assess the prognostic value of the factor V Leiden (FVL) and prothrombin (PT) mutations for the subsequent chance of live birth for women...

  12. Management of Venous Thromboembolism in Patients with Hereditary Antithrombin Deficiency and Pregnancy: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Mohammad Refaei

    2017-01-01

    Full Text Available Background. Hereditary antithrombin deficiency is a thrombogenic disorder associated with a 50–90% lifetime risk of venous thromboembolism (VTE, which is increased during pregnancy and the puerperium in these patients. We present a case of a woman with antithrombin (AT deficiency who presented with a VTE despite therapeutic low molecular weight heparin (LMWH. Though the pregnancy was deemed unviable, further maternal complications were mitigated through the combined use of therapeutic anticoagulation and plasma-derived antithrombin concentrate infusions to normalize her functional antithrombin levels. Methods. A review of the literature was conducted for studies on prophylaxis and management of VTE in pregnant patients with hereditary AT deficiency. The search involved a number of electronic databases, using combinations of keywords as described in the text. Only English language studies between 1946 and 2015 were included. Conclusion. Antithrombin concentrate is indicated in pregnant women with hereditary AT deficiency who develop VTE despite being on therapeutic dose anticoagulation. Expert opinion suggests AT concentrate should be used concomitantly with therapeutic dose anticoagulation. However, further high-quality studies on the dose and duration of treatment in the postpartum period are required. Use of AT concentrate for prophylaxis is controversial and should be based on individual VTE risk stratification.

  13. Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

    Science.gov (United States)

    2009-01-01

    In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504

  14. An investigation on clinical radiological diagnosis of hereditary osteogenesis imperfect (a report of 42 patients in a family)

    International Nuclear Information System (INIS)

    He Junxiang; Jiang Xuzhou; Zhang Shunzhi; Huang Guomei; Mu Huinian; Li Yi; Li Meihe

    1998-01-01

    Purpose: To investigate the main points of diagnosing hereditary osteogenesis imperfect. Methods: Retrospective analysis of clinical and radiological diagnosis of hereditary osteogenesis imperfect was done in 35 surviving patients and 7 deaths in a family. Results: (1) A family was described in which hereditary osteogenesis imperfect occurred in 5 generations. Forty-two patients (18 males, 24 females) ranged in age from 10 months to 67 years. (2) Both modes of inheritance existed simultaneously (dominant in 35 patients, recessive in 7 patients). (3) Blue sclera of different shades was found in all 42 patients. (4) Radiological change of bone was recognised in 35 surviving patients. The conditions were as follows: in 29 patients, general decreased bone density, thin bone cortex and long slender tubular bones were observed; six patients were normal; twenty-two patients had fracture. (5) Twenty-four patients (including 3 deaths) suffered form progressive deafness. (6) Twenty-one patients (including 3 deaths) had the triad of blue sclera, osteopsathyrosis and progressive deafness. (7) An increase in alkaline phosphatase level (in 17 patients) was confirmed by the tests in our laboratory. Conclusion: The authors suggested that the triad of blue sclera, osteopsathyrosis and progressive deafness is the characteristic manifestations of the disease, especially blue sclera, which may be regarded as an initial and suggestible physical sign, and an essential criterion for diagnosis

  15. Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study.

    Science.gov (United States)

    Fewings, Eleanor; Larionov, Alexey; Redman, James; Goldgraben, Mae A; Scarth, James; Richardson, Susan; Brewer, Carole; Davidson, Rosemarie; Ellis, Ian; Evans, D Gareth; Halliday, Dorothy; Izatt, Louise; Marks, Peter; McConnell, Vivienne; Verbist, Louis; Mayes, Rebecca; Clark, Graeme R; Hadfield, James; Chin, Suet-Feung; Teixeira, Manuel R; Giger, Olivier T; Hardwick, Richard; di Pietro, Massimiliano; O'Donovan, Maria; Pharoah, Paul; Caldas, Carlos; Fitzgerald, Rebecca C; Tischkowitz, Marc

    2018-04-26

    Germline pathogenic variants in the E-cadherin gene (CDH1) are strongly associated with the development of hereditary diffuse gastric cancer. There is a paucity of data to guide risk assessment and management of families with hereditary diffuse gastric cancer that do not carry a CDH1 pathogenic variant, making it difficult to make informed decisions about surveillance and risk-reducing surgery. We aimed to identify new candidate genes associated with predisposition to hereditary diffuse gastric cancer in affected families without pathogenic CDH1 variants. We did whole-exome sequencing on DNA extracted from the blood of 39 individuals (28 individuals diagnosed with hereditary diffuse gastric cancer and 11 unaffected first-degree relatives) in 22 families without pathogenic CDH1 variants. Genes with loss-of-function variants were prioritised using gene-interaction analysis to identify clusters of genes that could be involved in predisposition to hereditary diffuse gastric cancer. Protein-affecting germline variants were identified in probands from six families with hereditary diffuse gastric cancer; variants were found in genes known to predispose to cancer and in lesser-studied DNA repair genes. A frameshift deletion in PALB2 was found in one member of a family with a history of gastric and breast cancer. Two different MSH2 variants were identified in two unrelated affected individuals, including one frameshift insertion and one previously described start-codon loss. One family had a unique combination of variants in the DNA repair genes ATR and NBN. Two variants in the DNA repair gene RECQL5 were identified in two unrelated families: one missense variant and a splice-acceptor variant. The results of this study suggest a role for the known cancer predisposition gene PALB2 in families with hereditary diffuse gastric cancer and no detected pathogenic CDH1 variants. We also identified new candidate genes associated with disease risk in these families. UK Medical

  16. Hereditary onchyo-osteo-arthrodysplasia (nail-patella syndrome) with progressive renal failure

    International Nuclear Information System (INIS)

    Stellamor, K.; Anzboeck, W.

    1989-01-01

    A case of a fully developed hereditary onycho-osteo-arthrodysplasia (nail-patella syndrome) is presented. The typical signs, such as the iliac horns or variations of the knees, cubitals and nails should be familiar to every radiologist. The associated nephropathy seems to be caused by typical changes in the glomerular basement membrane seen in electron microscopy. Asymptomatic proteinuria is found in about 60% of the cases, in 5,5-8% the disease leads to the necessity of haemodialysis because of renal insufficiency. Hence, early diagnosis is very important. (orig.) [de

  17. Women’s Satisfaction with Genetic Counseling for Hereditary Breast-Ovarian Cancer: Psychological Aspects

    OpenAIRE

    Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.

    2004-01-01

    Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...

  18. Distinctions in sensitivity and repair of cells of children with some hereditary diseases

    International Nuclear Information System (INIS)

    Zasukhina, G.D.; Barashnev, Yu.I.; Vasil'eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N.

    1982-01-01

    A study was made of blood cell sensitivity of children, with some hereditary diseases, to ν-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes

  19. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

    Czech Academy of Sciences Publication Activity Database

    Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

    2016-01-01

    Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

  20. The technical hereditary of CWD

    International Nuclear Information System (INIS)

    Smulders, P.T.

    1990-01-01

    An overview is given of the activities of the Dutch foundation CWD since 1975. The financing of the foundation stopped July 1st 1990. From 1975 the CWD stimulated the use of small scale wind energy to pump up water in developing countries. The hereditary of the CWD consists of knowledge of the design and performance of components of wind mills, knowledge to design integral systems based on these components and preconditions, and knowledge how to manufacture, install and maintain the wind mills locally. The CWD designed three wind mill pumps of which 250 have been brought into operation in developing countries. A CWD-type pump was developed in Sri-Lanka of which 150 pumps were installed. Also attention is paid to the external situation which effected the CWD activities: the lack of interest from the Dutch industry to cooperate in developing CWD pumps; the actual market far away in developing countries; and too little competition in the research and development. The nature of the CWD-participants caused some internal friction which did not contribute to the effectivity of the CWD organisation. It is recommended to continue the development and testing of small wind energy systems and to preserve the knowledge gained by the CWD. 3 figs., 2 tabs., 3 refs

  1. Surgical hip dislocation according to Ganz for excision of osteochondromas in patients with multiple hereditary exostoses

    NARCIS (Netherlands)

    Sorel, J. C.; Façee Schaeffer, M.; Homan, A. S.; Scholtes, V. A B; Kempen, D. H R; Ham, S. J.

    2016-01-01

    Aims We report a prospective cohort study of the midterm results of surgical dislocation of the hip (according to Ganz) to perform resection of osteochondromas involving the femoral neck in patients with multiple hereditary exostoses (MHE). Methods Hip range of movement (ROM) was assessed pre-and

  2. Does calf muscle spasticity contribute to postural imbalance? A study in persons with pure hereditary spastic paraparesis

    NARCIS (Netherlands)

    Niet, M. de; Weerdesteyn, V.G.M.; Bot, S.T. de; Warrenburg, B.P.C. van de; Geurts, A.C.H.

    2013-01-01

    OBJECTIVES: The contribution of spasticity to postural imbalance in patients with upper motor neuron syndrome is still unclear. This study aimed to evaluate the responses to support-surface perturbations in patients with hereditary spastic paraparesis (HSP). These patients typically suffer from

  3. Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ekstrand, Anna Isinger; Jönsson, Mats; Lindblom, Annika

    2010-01-01

    The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT......, and PTEN in colorectal cancers linked to hereditary nonpolyposis colorectal cancer (HNPCC). Sequencing was used to identify mutations in PIK3CA, a real-time PCR-based method to identify KRAS mutations, and immunohistochemical staining was used to evaluate the expression of PIK3CA, phosphorylated AKT...... and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59...

  4. Leber's Hereditary Optic Neuropathy: A Case Report

    Directory of Open Access Journals (Sweden)

    Chi-Wu Chang

    2003-10-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease that primarily affects the optic nerve, causing bilateral vision loss in juveniles and young adults. A 12-year-old boy had complained of blurred vision in both eyes for more than 1 year. His best-corrected visual acuity was 0.08 in the right eye and 0.1 in the left. Ophthalmologic examination showed bilateral optic disc hyperemia and margin blurring, peripapillary telangiectasis, and a relative afferent pupil defect in his right eye. Fluorescein angiography showed no stain or leakage around the optic disc in the late phase. Visual field analysis showed central scotoma in the left eye and a near-total defect in the right. Upon examination of the patient's mitochondrial DNA, a point mutation at nucleotide position 11778 was found, and the diagnosis of LHON was confirmed. Coenzyme Q10 was used to treat the patient.

  5. Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

    OpenAIRE

    Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

    2009-01-01

    Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differe...

  6. Molecular Analysis: Microsatellite Instability and Loss of Heterozygosity of Tumor Suppressor Gene in Hereditary Non-Polyposis Colorectal Cancer (HNPCC

    Directory of Open Access Journals (Sweden)

    Vesna Hadžiavdić

    2009-02-01

    Full Text Available HNPCC (Hereditary non-polyposis colorectal cancer development is caused by mutation of genes included in system of mismatch repair genes. The mutation exists at 60% of patients in hMSH2 gene, 30% in hMLH1 and 10% both in hPMS1and hPMS2 genes. RER+ exists in about 90% in hereditary non-polyposis colorectal cancer and about 15-28% in sporadic cancers.The purpose of the study was to determine highly sensitive microsatellite markers which can be fast and efficient way of microsatellite screening for detection of HNPCC patients. Moreover, we have analysed the loss of heterozygosity of tumour suppressor genes which could have the diagnostic value in detection of HPNCC patients.

  7. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

    Directory of Open Access Journals (Sweden)

    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions.

  8. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

    Directory of Open Access Journals (Sweden)

    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions

  9. Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    M. H. Sun

    2004-01-01

    Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.

  10. Prognostic factors for hereditary cancer distress six months after BRCA1/2 or HNPCC genetic susceptibility testing

    NARCIS (Netherlands)

    van Oostrom, Iris; Meijers-Heijboer, Hanne; Duivenvoorden, Hugo J.; Brocker-Vriends, Annette H. J. T.; van Asperen, Christi J.; Sijmons, Rolf H.; Seynaeve, Caroline; Van Gool, Arthur R.; Klijn, Jan G. M.; Tibben, Aad

    This study explored predictors for hereditary cancer distress six months after genetic susceptibility testing for a known familial BRCA1/2 or HNPCC related mutation, in order to gain insight into aspects relevant for the identification of individuals needing additional psychosocial support. Coping,

  11. Recognition and management of hereditary colorectal cancer syndromes Identificación y tratamiento de los síndromes de cáncer colorrectal hereditario

    Directory of Open Access Journals (Sweden)

    M. Herráiz

    2009-02-01

    Full Text Available Over 1.900 colorectal tumors will arise in association with a hereditary colorectal cancer syndrome in Spain in 2009. The genetic defects responsible for the most common syndromes have been discovered in recent years. Genetic testing helps diagnose affected individuals and allows identification of individuals at-risk. Colonoscopy and prophylactic colectomy decrease colorectal cancer incidence and overall mortality in patients with hereditary colon cancer. Extracolonic tumors are frequent in these syndromes, so specific surveillance strategies should be offered.

  12. Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

    Science.gov (United States)

    Li, Junyan; Jing, Ruilin; Wei, Hongyi; Wang, Minghao; Qi, Xiaowei; Liu, Haoxi; Liu, Jian; Ou, Jianghua; Jiang, Weihua; Tian, Fuguo; Sheng, Yuan; Li, Hengyu; Xu, Hong; Zhang, Ruishan; Guan, Aihua; Liu, Ke; Jiang, Hongchuan; Ren, Yu; He, Jianjun; Huang, Weiwei; Liao, Ning; Cai, Xiangjun; Ming, Jia; Ling, Rui; Xu, Yan; Hu, Chunyan; Zhang, Jianguo; Guo, Baoliang; Ouyang, Lizhi; Shuai, Ping; Liu, Zhenzhen; Zhong, Ling; Zeng, Zhen; Zhang, Ting; Xuan, Zhaoling; Tan, Xuanni; Liang, Junbin; Pan, Qinwen; Chen, Li; Zhang, Fan; Fan, Linjun; Zhang, Yi; Yang, Xinhua; Li, Jingbo; Chen, Chongjian; Jiang, Jun

    2018-05-12

    Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n=937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n=18), PALB2 (n=11), CHEK2 (n=6), ATM (n=6), and BARD1 (n=5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes. This article is protected by copyright. All rights reserved. © 2018 UICC.

  13. Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability

    OpenAIRE

    Umar, Asad; Boland, C. Richard; Terdiman, Jonathan P.; Syngal, Sapna; de la Chapelle, Albert; Rüschoff, Josef; Fishel, Richard; Lindor, Noralane M.; Burgart, Lawrence J.; Hamelin, Richard; Hamilton, Stanley R.; Hiatt, Robert A.; Jass, Jeremy; Lindblom, Annika; Lynch, Henry T.

    2004-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Because cancers with MSI account for approximately 15% of all colorectal cancers and because of the need for a better understanding of the clinical and histologic manifestations of HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in 1996, which led to...

  14. Distinctions in sensitivity and repair of cells of children with some hereditary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Zasukhina, G.D.; Barashnev, Yu.I.; Vasil' eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N. (AN SSSR, Moscow. Inst. Obshchej Genetiki)

    A study was made of blood cell sensitivity of children with some hereditary diseases, to ..gamma..-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes.

  15. Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Poulsen, Henrik E; Weimann, Allan

    2009-01-01

    Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method...... of the iron overload seen in this disease. By this mechanism cellular damage resulting in end organ damage, typically seen in the liver of such patients, may be mediated....

  16. In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11.

    Directory of Open Access Journals (Sweden)

    Rita-Eva Varga

    2015-08-01

    Full Text Available Hereditary spastic paraplegia (HSP is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs. Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice.

  17. [Hereditary heterozygous factor VII deficiency in patients undergoing surgery : Clinical relevance].

    Science.gov (United States)

    Woehrle, D; Martinez, M; Bolliger, D

    2016-10-01

    A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients. In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution. We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution. Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

  18. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...

  19. Re-emergence of hereditary polyneuropathy in scandinavian alaskan malamute dogs-old enemy or new entity? A case series

    DEFF Research Database (Denmark)

    Jäderlund, Karin Hultin; Rohdin, Cecilia; Berendt, Mette

    2017-01-01

    A homozygous mutation has been identified in the N-myc downstream-regulated gene 1 (NDRG1) in recent cases of polyneuropathy in Alaskan malamute dogs from the Nordic countries and USA. The objective of the present study was to determine if cases diagnosed 30-40 years ago with polyneuropathy...... in the Alaskan malamute breed in Norway had the same hereditary disease as the recent cases. Fourteen historical cases and 12 recently diagnosed Alaskan malamute dogs with hereditary polyneuropathy, and their parents and littermates (n = 88) were included in this study (total n = 114). After phenotyping...... of historical and recent cases, NDRG1 genotyping was performed using DNA extracted from archived material from five Norwegian dogs affected by the disease in the late 1970s and 1980s. In addition, pedigrees were analysed. Our study concluded that historical and recent phenotypic polyneuropathy cases were...

  20. CLINICAL APPROACH TO HEREDITARY HEMORRHAGIC TELANGIECTASIA

    Directory of Open Access Journals (Sweden)

    Mary Hachmeriyan

    2013-11-01

    Full Text Available Background: Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber disease is a rare syndrome, inherited as an autosomal dominant trait with incidence of 1/10000. The clinical manifestations are due to vascular malformations and predisposition to hemorrhages in different organs, the leading symptom being recurrent epistaxis. If diagnosed with HHT, the patient and his relatives and especially children have to be screened for occult vascular malformations.Case report: A 30 years old woman was treated for cerebral stroke, epistaxis, anemia, arterio-venous malformations for over 6 months. Only at this point she was diagnosed with HHT, after noticing the typical mucosal changes. Focused family history revealed symptoms of HHT in her only child, her father, aunt and two cousins The child was screened for occult vascular malformations – attainment of the nasal mucosa, lungs, gastrointestinal system, liver and brain. Pulmonary and gastrointestinal arterio-venous malformations were proven.Conclusion: Any case of recurrent epistaxis should be evaluated for HHT. After confirmation of the diagnosis every patient and close relatives have to be screened for attainment of other organs and followed up in order to prevent severe life threatening complications.

  1. RBEs and cytogenetic hereditary effects induced by neutron beams in mice

    International Nuclear Information System (INIS)

    Du Zeji; Li Yanyi; Liu Degui

    1994-01-01

    The RBEs and cytogenetic hereditary effects of different dose of neutron beams on chromosome aberrations and micronuclei of bone marrow cells in mice were observed. The results indicated that micronuclei frequency of occurrence and chromosome aberration frequency caused by neutrons increased with doses. The relationship was feasible to Y aD n . The lower energy of neutrons had the smaller value of RBE. RBE determined by CSACR were larger than that by MNCF. RBEs decreased with increasing of neutron doses, especially within the low range of doses. There was a linear relationship between CSACR and MNCF caused by neutron beams and γ-ray

  2. Chondrosarcoma secondary to hereditary multiple exostosis treated by extended internal hemiplevectomy

    Directory of Open Access Journals (Sweden)

    Ademar Lopes

    Full Text Available The authors report on the case of a 28-year-old patient with extensive chondrosarcoma of the left ischium and pubis involving hip joint, skin, and soft tissue of the gluteal region, secondary to hereditary multiple exostosis submitted to an extended internal Enneking type II and Ill hemipelvectomy. No prosthesis or arthrodesis was used. A few years ago, patients with extensive tumors like this one were treated with interilioabdominal amputation, resulting in a loss of quality of Iife.Two years after the limb-preserving surgery, this patient was disease free, with good functional results, including bipedal ambulation with support.

  3. Hereditary hemorrhagic telangiectasia: progress of diagnostic imaging and vascular therapeutic embolization

    International Nuclear Information System (INIS)

    Lu Chuan; Liu Zuoqin

    2008-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a genetic autosomal-dominant disorder characterized by the presence of epistaxis, vascular telangiectasis in mucosal and cutaneous tissues, with visceral lesions and family history. However, many specialists or radiologists are still in lack of appreciation concerning the full range of consequences in diagnosis and their family relationship resulting the poor recognition of the disease. Understanding the diagnostic imaging and therapeutic measure for HHT will be critical, because of the continuous growth and risk existance of these arteriovenous malformations arousing early diagnosis, proper treatment, adequate follow-up and screening of the family. (authors)

  4. Psychological distress and breast self-examination frequency in women at increased risk for hereditary or familial breast cancer

    NARCIS (Netherlands)

    van Dooren, S.; Rijnsburger, A. J.; Seynaeve, C.; Kriege, A.; Duivenvoorden, H. J.; Bartels, C. C. M.; Essink-Bot, M. L.; de Koning, H. J.; Tibben, A.

    2003-01-01

    BACKGROUND: The Magnetic Resonance Imaging Screening study evaluates the efficacy and psychological impact of a surveillance program for women at increased risk for hereditary or familial breast cancer in the Netherlands. Surveillance consists of biannual physical examination, annual mammography,

  5. Identification of a new mutation in an Iranian family with hereditary multiple osteochondromas

    Directory of Open Access Journals (Sweden)

    Akbaroghli S

    2016-12-01

    Full Text Available Susan Akbaroghli,1,* Maryam Balali,2,* Behnam Kamalidehghan,3,4 Siamak Saber,4 Omid Aryani,5 Goh Yong Meng,6 Massoud Houshmand4 1Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, 2ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences (IUMS, 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, 4Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology, 5Department of Neuroscience, Iran Medical University, Tehran, Iran; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM, Serdang, Malaysia *These authors contributed equally to this work Background: Hereditary multiple osteochondromas (HMO, previously named hereditary multiple exostoses (HME, is an autosomal dominant skeletal disorder characterized by the growth of multiple osteochondromas and is associated with bony deformity, skeletal growth reduction, nerve compression, restriction of joint motion, and premature osteoarthrosis. HMO is genetically heterogeneous, localized on at least three chromosomal loci including 8q24.1 (EXT1, 11p11-p13 (EXT2, and 19p (EXT3. The median age of diagnosis is 3 years; almost all affected individuals are diagnosed by age 12. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk of malignant degeneration is low (~1%.Methods and results: This study was performed on an Iranian family with nine affected individuals from three consecutive generations. Here, the proband was an affected woman who received genetic counseling prior to pregnancy. All exons of the three genes were examined in the proband using polymerase chain reaction and sequencing methods (the last member of this family is a male with severe deformities and lesions, especially around his large joints. Exon 4 of EXT1 (c.1235 G>A was changed in affected

  6. The Design of Studies to Evaluate Hereditary and Environmental Contributions to the Etiology of Behavioral Disorders.

    Science.gov (United States)

    Rosenthal, David

    The introductory discussion focuses on the change in the current scientific climate regarding the role of heredity in the etiology of behavioral disorders. The author and his colleagues embarked on a series of studies, using naturally occurring adoptions as their subject source, to tease apart hereditary and environmental factors thought to be…

  7. Movement disorders in hereditary ataxias.

    Science.gov (United States)

    Garcia Ruiz, Pedro J; Mayo, David; Hernandez, Jaime; Cantarero, Susana; Ayuso, Carmen

    2002-10-15

    Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA. Copyright 2002 Elsevier Science B.V.

  8. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance

    NARCIS (Netherlands)

    Hendriks, Yvonne M. C.; Wagner, Anja; Morreau, Hans; Menko, Fred; Stormorken, Astrid; Quehenberger, Franz; Sandkuijl, Lodewijk; Møller, Pal; Genuardi, Maurizio; van Houwelingen, Hans; Tops, Carli; van Puijenbroek, Marjo; Verkuijlen, Paul; Kenter, Gemma; van Mil, Anneke; Meijers-Heijboer, Hanne; Tan, Gita B.; Breuning, Martijn H.; Fodde, Riccardo; Wijnen, Juul Th; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans

    2004-01-01

    BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20

  9. Clinical and neurophysiologic characterization of an European family with hereditary sensory neuropathy, paroxysmal cough and gastroesophageal reflux

    Directory of Open Access Journals (Sweden)

    Pedro Barros

    2014-04-01

    Full Text Available In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. Objective: To study a new Portuguese family with these characteristics. Method: To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Results: Three of five siblings presented a similar history of paroxysmal cough (5th decade. About a decade later they experienced numbness and paraesthesia in the feets and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Discussion: Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

  10. Clinical and neurophysiologic characterization of an European family with hereditary sensory neuropathy, paroxysmal cough and gastroesophageal reflux.

    Science.gov (United States)

    Barros, Pedro; Morais, Hugo; Santos, Catarina; Roriz, José; Coutinho, Paula

    2014-04-01

    In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. To study a new Portuguese family with these characteristics. To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Three of five siblings presented a similar history of paroxysmal cough (5th decade). About a decade later they experienced numbness and paraesthesia in the feet and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

  11. Prophylactic total gastrectomy in hereditary diffuse gastric cancer

    DEFF Research Database (Denmark)

    Bardram, Linda; Hansen, Thomas V O; Gerdes, Anne-Marie

    2014-01-01

    Inactivating mutations in the CDH1 (E-cadherin) gene are the predisposing cause of gastric cancer in most families with hereditary diffuse gastric cancer (HDGC). The lifetime risk of cancer in mutation positive members is more than 80 % and prophylactic total gastrectomy is recommended. Not all...... mutations in the CDH1 gene are however pathogenic and it is important to classify mutations before this major operation is performed. Probands from two Danish families with gastric cancer and a history suggesting HDGC were screened for CDH1 gene mutations. Two novel CDH1 gene mutations were identified....... Hospital stay was 6-8 days and there were no complications. Small foci of diffuse gastric cancer were found in all patients-intramucosal in six and advanced in one. Preoperative endoscopic biopsies had revealed a microscopic cancer focus in two of the patients. Our data confirmed the pathogenic nature...

  12. Hereditary ectodermal dysplasia: Report of 11 patients from a family

    Directory of Open Access Journals (Sweden)

    Seema Vaidya

    2013-01-01

    Full Text Available Hereditary Ectodermal Dysplasia is an inherited disorder commonly involving skin, teeth, hair, and nails. We have observed ectodermal dysplasia (EDs in 11 individuals over two generations in one family. Smooth, dry, thin skin was seen in most affected individuals. All had fine, slow-growing scalp hair and body hair and some had sparse eyebrows and short eyelashes. Nearly all showed decrease in sweating. Severe teeth abnormalities were seen in all patients and fingernail abnormalities were not so severe but toenail abnormalities were seen in all patients. No other abnormalities were seen in affected individuals in this family. It is very rare to find such a large family having ectodermal dysplasia.

  13. Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P).

    Science.gov (United States)

    Campellone, Joseph V

    2013-06-01

    Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P) is a rare disorder inherited in an autosomal dominant fashion. Patients present with slowly progressive proximal-predominant weakness, painful muscle cramps, fasciculations, large-fiber sensory loss, and areflexia. Electrodiagnostic (EDX) studies typically reveal abnormalities consistent with a sensorimotor neuronopathy. A patient with HMSN-P underwent EDX studies, revealing ongoing and chronic neurogenic denervation, motor unit instability, and neuromyotonic discharges, further defining the spectrum of EDX findings in HMSN-P. The clinical, pathological, and genetic features are also reviewed. The appearance of HMSN-P in the United States and elsewhere calls for clinicians in nonendemic regions to be familiar with this rare disorder, which has typically been geographically confined.

  14. The hereditary angioedema burden of illness study in Europe (HAE-BOIS- Europe)

    DEFF Research Database (Denmark)

    Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa

    2012-01-01

    ABSTRACT: BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation...... of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect...

  15. Imaging features of type 1 hereditary tyrosinemia: a review of 30 patients

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, J. [Department of Radiology, Hopital Sainte-Justine, Montreal, Que. (Canada); Garel, L. [Department of Radiology, Hopital Sainte-Justine, Montreal, Que. (Canada); Patriquin, H. [Department of Radiology, Hopital Sainte-Justine, Montreal, Que. (Canada); Paradis, K. [Department of Pediatrics, Gastroenterology, Universite de Montreal, Que. (Canada); Forget, S. [Department of Pediatrics, Gastroenterology, Universite de Montreal, Que. (Canada); Filiatrault, D. [Department of Radiology, Hopital Sainte-Justine, Montreal, Que. (Canada); Grignon, A. [Department of Radiology, Hopital Sainte-Justine, Montreal, Que. (Canada); Russo, P. [Department of Pathology, Hopital Sainte-Justine, Montreal, Que. (Canada); St-Vil, D. [Department of Surgery, Hopital Sainte-Justine, Montreal, Que. (Canada)

    1996-12-01

    Hereditary tyrosinemia type 1, a common genetic disorder in the province of Quebec, is characterized by a deficiency of fumarylacetoacetate hydrolase. In this autosomal recessive disorder of tyrosine metabolism, the accumulation of succinylacetone leads to neurologic crises, acute and chronic liver failure, complex renal tubulopathy, rickets and a hemorrhagic syndrome. Liver trans- plantation has dramatically modified the spontaneous course of this lethal disease. The present paper describes the imaging fea- tures of tyrosinemia in 30 patients followed from 1980 to 1995 at Hopital Sainte-Justine, Montreal, Canada. (orig.). With 10 figs., 2 tabs.

  16. Hereditary retinal eye diseases in childhood and youth affecting the central retina

    Directory of Open Access Journals (Sweden)

    Martin M Nentwich

    2013-01-01

    Classic examinations for patients suffering from hereditary retinal dystrophies of the central retina are funduscopy - also using red-free light - visual-field tests, electrophysiologic tests as electro-retinogram [ERG] and multifocal ERG and tests evaluating color vision. Recently, new imaging modalities have been introduced into the clinical practice. The significance of these new methods such as high-resolution spectral-domain optic coherence tomography [SD-OCT] and fundus autofluorescence will be discussed as well as "next generation sequencing" as a new method for the analysis of genetic mutations in a larger number of patients.

  17. Motor activation in SPG4-linked hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Scheuer, KH; Nielsen, JE; Krabbe, Katja

    2006-01-01

    OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS......: Thirteen patients and 13 normal controls matched for age, gender and handedness underwent O15-labelled water positron emission tomography during (1) right ankle flexion-extension, (2) right shoulder flexion-extension and (3) rest. Within-group comparisons of movement vs. rest (simple main effects......, the supplementary motor areas and the right premotor cortex compared to controls. CONCLUSIONS: Motor cortical reorganisation may explain this result, but as no significant differences were recognised in the motor response of the unaffected limb, differences in functional demands should also be considered...

  18. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test

    NARCIS (Netherlands)

    Curvers, J; Thomassen, MCLGD; Rimmer, J; Hamulyak, K; van der Meer, J; Tans, G; Preston, FE; Rosing, J

    Background. Several hereditary and acquired risk factors for venous thromboembolism (VTE) are associated with impaired down-regulation of thrombin formation via the protein C pathway. To identify individuals at risk, functional tests are needed that estimate the risk to develop venous thrombosis.

  19. Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation: further clinical and histological characterization in a patient.

    Science.gov (United States)

    König, P; Ambrose, N S; Scott, N

    2000-01-01

    Hereditary internal anal sphincter myopathy is a very rare condition, only three families have so far been described in the literature. In this case report further clinical and histological findings of one affected member of one of the above families are presented.

  20. An ochre mutation in the vitamin D receptor gene causes hereditary 1,25-dihydroxyvitamin D3-resistant rickets in three families

    International Nuclear Information System (INIS)

    Ritchie, H.H.; Hughes, M.R.; Thompson, E.T.; Pike, J.W.; O'Malley, B.W.; Malloy, P.J.; Feldman, D.; Hochberg, Z.

    1989-01-01

    Hereditary 1,25-dihydroxyvitamin D 3 -resistant rickets is a rare autosomal-recessive disease resulting from target-organ resistance to the action of the active hormonal form of vitamin D. Four affected children from three related families with the classical syndrome of hereditary 1,25-dihydroxyvitamin D 3 -resistant rickets and the absence of detectable binding to the vitamin D receptor (VDR) in cultured fibroblasts or lymphoblasts were examined for genetic abnormalities in the VDR gene. Genomic DNA from Epstein-Barr virus-transformed lymphoblasts of eight family members was isolated and amplified by polymerase chain reaction techniques. Amplified fragments containing the eight structural exons encoding the VDR protein were sequenced. The DNA from all affected children exhibited a single C → A base substitution within exon 7 at nucleotide 970. Although the affected children were all homozygotic for the mutation, the four parents tested all exhibited both wild-type and mutant alleles, indicating a heterozygous state. Recreated mutant receptor exhibited no specific 1,25-[ 3 H]dihydroxyvitamin D 3 binding and failed to activate a cotransfected VDR promoter-reporter gene construct. Thus these findings identify an ochre mutation in a human steroid hormone receptor in patients with hereditary 1,25-dihydroxyvitamin D 3 -resistant rickets