Sample records for achondroplasia

  1. Achondroplasia (United States)

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    Full Text Available Stunted growth of an individual occurs in many systemic conditions and the main cause is due to defective cartilage growth in the long bones particularly in the lower extremities. In achondroplasia and Ellis Van Creveld syndrome the endochondral ossification of long bones are affected but in Ellis Van Creveld syndrome, the stunted growth is associated with ectodermal dysplasia, polydactyly and cardiac diseases. The common feature for both achondroplasia and Ellis Van Creveld syndrome is the individual’s trunk is normal but the lower extremities are short. Though there is a cartilage dysfunction in these two cases, different clinical manifestation occurs in the body and these things are recorded from two case reports of Achondroplasia and Ellis Van Creveld syndrome and submitted the clinical differences with explanation and discussion.

  3. Achondroplasia: Craniofacial manifestations and considerations in dental management


    Al-Saleem,Afnan; Al-Jobair, Asma


    Achondroplasia is the most common form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of dental interest because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require special precautions during dental management. Craniofacial manifestations and c...

  4. Prenatal Diagnosis of Concurrent Achondroplasia and Klinefelter Syndrome

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    Esther Perez-Carbajo


    Full Text Available Achondroplasia is the most frequent nonlethal skeletal dysplasia, with a prevalence of 1 : 5000 to 1 : 40,000 live births, and it is caused by a fibroblast growth factor receptor alteration. The combination of achondroplasia and Klinefelter syndrome is extremely rare and just four reports have been published in the literature, which were all diagnosed postnatally. We report the fifth case described of this uncommon association and its prenatal diagnosis. In cases of prenatal diagnosis of achondroplasia with additional suspicious morphological abnormalities, an invasive test such as amniocentesis must be carried out to assess the karyotype normality.

  5. Sagging rope sign in achondroplasia is different from Perthes disease. (United States)

    Oh, Chang-Wug; Shingade, Viraj Uttamrao; Song, Hae-Ryong; Suh, Seung-Woo; Hong, Jun-Seok; Lee, Seok-Hyun


    The "sagging rope" sign is a radiopaque line seen on radiographs of hips with Perthes disease. The main purpose of this study was to determine the incidence, cause, and importance of this sign in achondroplasia and to reveal how it differs from in Perthes disease. Serial radiograms, along with two- and three-dimensional CT images were studied in 42 patients with achondroplasia. The sign was observed bilaterally in all patients. Evaluation of CT images revealed spherical heads with the presence of circumferential overhang in all hips. This circumferential overhang seen on three-dimensional CT images corresponded to the sagging rope sign on plain radiographs. The presence of the sagging rope sign in bilateral hips is a characteristic feature of achondroplasia. It usually appears before epiphyseal closure. Its cause, incidence, and nature differ from in Perthes disease, and its presence does not carry a negative prognosis in achondroplasia.

  6. Physeal growth arrest after tibial lengthening in achondroplasia


    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong


    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who und...

  7. Sleep and upper airway obstruction in children with achondroplasia

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    Zucconi, M; Weber, G; Castronovo, [No Value; FeriniStrambi, L; Russo, F; Chiumello, G; Smirne, S


    Objective: The features of achondroplasia, the most common form of dwarfism, includes short cranial base and midface hypoplasia; both abnormalities increased the risk of upper airway obstruction during sleep, The aim of our study was to evaluate sleep and respiratory function of children with achond

  8. Development in Children with Achondroplasia: A Prospective Clinical Cohort Study (United States)

    Ireland, Penelope J.; Donaghey, Samantha; McGill, James; Zankl, Andreas; Ware, Robert S.; Pacey, Verity; Ault, Jenny; Savarirayan, Ravi; Sillence, David; Thompson, Elizabeth; Townshend, Sharron; Johnston, Leanne M.


    Aim: Achondroplasia is characterized by delays in the development of communication and motor skills. While previously reported developmental profiles exist across gross motor, fine motor, feeding, and communication skills, there has been no prospective study of development across multiple areas simultaneously. Method: This Australasian…

  9. Physeal growth arrest after tibial lengthening in achondroplasia (United States)


    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Results Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Interpretation Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence—especially when lengthening of more than 50% is attempted. PMID:22489887

  10. Correction of anterior open bite in a case of achondroplasia

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    Karpagam S


    Full Text Available Treatment planning for patients with skeletal deformities is often considered challenging. This article reports a female patient with achondroplasia who presented with severe maxillary retrognathism and vertical excess along with anterior open bite. The clinical and cephalometric findings of the patient are detailed here. The treatment plan consisted of modified anterior maxillary osteotomy for simultaneous vertical and sagittal augmentation along with orthodontic intervention. The course of surgical-orthodontic treatment and the results are presented. This treatment is to be followed by correction of vertical maxillary excess after completion of growth. This paper concludes that the dentoalveolar component of a skeletal deformity can be handled independent of the craniofacial management.

  11. Fixator-Assisted Lengthening and Deformity Correction Over an Intramedullary Nail in a Patient with Achondroplasia

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    Erdal Uzun


    Full Text Available Achondroplasia is the most frequently encountered form of nonlethal skeletal dysplasia and a type of rhizomelic dwarfism. It results in considerable physical and psychologic handicaps owing to the disproportionate stature of the body and difficulty in performing routine activities of daily living. They also have major musculoskeletal problems including symptomatic malalignment of the lower limbs. Limb lengthening has been used in patients with achondroplasia by different techniques (Intramedullar nailing, monolateral or circular external fixator. We report our treatment of a patient 17 years of age with achondroplasia for bilateral lower limb length discrepancy and bilateral tibial varus deformity.

  12. Growth hormone treatment in 35 prepubertal children with achondroplasia

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    Hertel, Niels Thomas; Eklöf, Ole; Ivarsson, Sten


    BACKGROUND: Achondroplasia is a skeletal dysplasia with extreme, disproportionate, short stature. AIM: In a 5-y growth hormone (GH) treatment study including 1 y without treatment, we investigated growth and body proportion response in 35 children with achondroplasia. METHODS: Patients were...... randomized to either 0.1 IU/kg (n = 18) or 0.2 IU/kg (n = 17) per day. GH treatment was interrupted for 12 mo after 2 y of treatment in prepubertal patients to study catch-down growth. Mean height SDS (HSDS) at start was -5.6 and -5.2 for the low- and high-dose groups, respectively, and mean age 7.3 and 6.......6 y. RESULTS: Mean growth velocity (baseline 4.5/4.6 cm/y for the groups) increased significantly by 1.9/3.6 cm/y during the first year and by 0.5/1.5 cm/y during the second year. During the third year, a decrease of growth velocity was observed at 1.9/1.3 cm/y below baseline values. HSDS increased...

  13. Magnetic resonance evaluation of the knee in children and adolescents with achondroplasia

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    Akyol, Yakup; Averill, Lauren W. [Nemours/Alfred I. duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Atanda, Alfred; Mackenzie, William G. [Nemours/Alfred I. duPont Hospital for Children, Department of Orthopedics, Wilmington, DE (United States); Kecskemethy, Heidi H. [Nemours/Alfred I. duPont Hospital for Children, Department of Medical Imaging, Wilmington, DE (United States); Nemours/Alfred I. duPont Hospital for Children, Department of Biomedical Research, Wilmington, DE (United States); Bober, Michael B. [Nemours/Alfred I. duPont Hospital for Children, Division of Genetics, Department of Pediatrics, Wilmington, DE (United States)


    Achondroplasia is the most common form of skeletal dysplasia. Although the radiographic features are well described, MRI features of the knee in achondroplasia have not been reported. To describe common MRI characteristics of the knee joint in symptomatic children and adolescents with achondroplasia. We retrospectively evaluated 10 knee MRI examinations in 8 children and young adults (age range 11-20 years, mean 16.3 years) with achondroplasia. We measured modified Insall-Salvati index, knee flexion angle, anterior cruciate ligament (ACL)-Blumensaat line angle, ACL-tibial angle, posterior cruciate ligament (PCL) angle, intercondylar notch width index, and intercondylar notch depth index. We compared our findings with an age- and gender-matched control group of 20 children (age range 15-18 years; mean 16 years) with normal knee MRIs. All 10 knees in the achondroplasia group had discoid lateral meniscus; 8 meniscal tears were identified. Patella baja was present in half of the study cases. Greater knee flexion and increased ACL-Blumensaat line and PCL angles were seen in all achondroplasia knees. ACL-tibial angle was similar in the study and in the control group. Children with achondroplasia had deeper A-shape femoral notches that extended more anteriorly than those seen in the control group. MRI findings were confirmed in all seven knees with arthroscopic correlation. Discoid lateral meniscus, often with tear, is a consistent feature in knee MRIs of symptomatic children and adolescents with achondroplasia. Other findings include patella baja, knee flexion, deep A-shape intercondylar notch, increased ACL-Blumensaat line angle and taut PCL. (orig.)

  14. A case report of recurrent achondroplasia in fetuses of normal parents

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    Anbumani TL


    Full Text Available Achondroplasia, a skeletal dysplasia has an incidence of 1 in 15000 to 1 in 30000 live births. It is inherited in an autosomal dominant manner. The occurrence of recurrent achondroplasia in babies born to normal parents is rare. The present case report is one such type. A female fetus of 27 weeks gestational age was brought to the Department of Anatomy, Karpaga Vinayaga Institute of Medical Sciences, Maduranthagam. There was frontal bossing of forehead, rhizomelic type of limb shortening with limitation of elbow extension in the fetus. The mother of the fetus, who is 26 years old, gave history of recurrence of such condition. Her first pregnancy was a twin pregnancy, conceived by natural methods, where one of the twins was a male baby who also had achondroplasia and died 2 hours after delivery. The other twin is a girl and the child has delayed developmental milestones. Her second pregnancy was uneventful. The present fetus under study is from her third pregnancy. Her marriage is of second degree consanguineous type. The age of her husband is 36 years old. Germinal mosaicism has been attributed for the causation of recurrent achondroplasia in children, whose parents are normal. 80% of achondroplasia is due to a new mutation. Only 20% of achondroplasia is inherited. Increased paternal age is a risk factor for new mutations to occur. The other investigations of the case and the genetic analysis are described further in the article. [Int J Res Med Sci 2015; 3(6.000: 1533-1537

  15. Achondroplasia and hypochondroplasia. Comments on frequency, mutation rate, and radiological features in skull and spine. (United States)

    Oberklaid, F; Danks, D M; Jensen, F; Stace, L; Rosshandler, S


    An attempt was made to ascertain all the dwarfs in the State of Victoria. The incidence of achondroplasia proved to be approximately 1 in 26,000 live births in the period 1969 to 1975 when ascertainment was nearly complete. This indicates a mutation rate of 1.93 X 10(-5) per generation in this locus. Paternal age was shown to influence mutation. Ascertainment in earlier years of the study was low despite the very great effort made to find all cases. Patients with hypochondroplasia were particularly difficult to find. However, 25 cases were found for study. Overlap between hypochondroplasia and achondroplasia was found in all features except the facial appearance (which was the basis of definition). Achondroplasia was more severe in all regards, but some individuals with hypochondroplasia were very short and some had extreme degrees of spinal canal stenosis. The classical measurements used to describe the skull changes in acondroplasia failed to distinguish this condition from hypochondroplasia. More efficient indices were devised, but visual assessment of the size of the facial region compared to that of the cranial valult proved more reliable than any index. The clinical distinction based upon facial appearance remains the arbitrary basis of definition.

  16. Deceleration in maturation of bone during adolescent age in achondroplasia - a retrospective study using RUS scoring system

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    Lee, Suk-Ha [Konkuk University Hospital, Department of Orthopedics, Seoul (Korea); Modi, Hitesh N.; Suh, Seung Woo [Korea University Guro Hospital, Scoliosis Research Institute, Department of Orthopedics, Seoul (Korea); Song, Hae-Ryong; Hazra, Sunit; Modi, Chetna [Korea University Guro Hospital, Rare Disease Institute, Department of Orthopedics, Seoul (Korea)


    Knowledge of bone age in achondroplasia is required for the prediction of adult height, timings of limb lengthening, and epiphysiodesis procedures. The purpose of this investigation was to determine the differences in skeletal age in achondroplasia and a control population with the Tanner-Whitehouse 3 method using the RUS score and to determine the right age for the interventional procedure for limb lengthening procedure or deformity correction in these patients. Left hand radiographs of 34 patients (age range, 5-18 years) with achondroplasia were evaluated for skeletal age using the RUS scoring system, which were compared with the left hand radiographs of 41 patients (age range, 5-18 years) without achondroplasia measuring skeletal age. The difference in chronological age and RUS bone age were evaluated statistically according to gender and age group. In the achondroplasia group, chronological age were 10.5{+-}4.3 years for males and 10.1{+-}3.6 years for females and RUS bone age were 9.2{+-}4.0 years for males and 8.9{+-}3.4 years for females, which showed statistically significantly difference (males p=0.0003 and females p < 0.0001), while in the control group, chronological age were 11.1{+-}2.9 years for males and 10.7{+-}3.4 years for females and RUS bone age were 11.2{+-}3.4 years for males and 10.7{+-}3.3 years for females, which did not show statistically significantly difference (males p=0.54 and females p=0.76). Our finding suggested a delay of 1.4 years for males and 1.2 years for females in the maturation of bone in achondroplasia patients. Difference between chronological age and RUS bone age was 0.9{+-}1.1 for <10 years and 1.6{+-}0.9 for >10 years in the study group, while 0.1{+-}1.1 for <10 years and -0.2 {+-} 0.6 for >10 years in the control group, which also showed >statistically significant difference (<10 years p=0.04 and >10 years p<0.0001). These differences indicate that there was a delay in the maturation of bones by 1 year in the group <10

  17. Magnetic resonance imaging study determining cord level and occupancy at thoracolumbar junction in achondroplasia - A prospective study

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    Hitesh N Modi


    Conclusion: Our results indicated high level of spinal cord in achondroplasia patients compared to nonachondroplasia individuals. High prevalence of neurological symptoms at TL level in such patients can be associated with high cord level and developing progressive kyphosis at TL level along with degenerative process.

  18. Achondroplasia with 47, xxy karyotype: a case report of the neonatal diagnosis of an extremely unusual association

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    Ros-Pérez Purificación


    Full Text Available Abstract Background The association of achondroplasia and Klinefelter syndrome is extremely rare. To date, five cases have been previously reported, all of them diagnosed beyond the postnatal period, and only one was molecularly characterized. We describe the first case of this unusual association diagnosed in the neonatal period, the clinical findings and the molecular studies undertaken. Case presentation The boy was born at term with clinical and radiological features indicating the diagnosis of achondroplasia or hypochondroplasia combined with the prenatal karyotype of Klinefelter syndrome (47,XXY. Neonatal FGFR3 mutation screening showed that the newborn was heterozygous for the classic achondroplasia G340R mutation. Microsatellite marker analysis showed that the sex chromosome aneuploidy had arisen from a non-disjunction error in paternal meiosis I, with a recombination event in the pseudoautosomal region 1 (PAR1. Conclusion Specific mutation analysis is appropriate to confirm the clinical diagnosis of achondroplasia for appropriate diagnosis, prognosis, and genetic counseling, especially when the karyotype does not explain the abnormal prenatal sonographic findings. In the present case, a recombination event was observed in the PAR1 region, although recombinational events in paternally derived Klinefelter syndrome cases are much rarer than expected.

  19. Common mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism

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    Bonaventure, J.; Rousseau, F.; Legeai-Mallet, L.; LeMerrer, M.; Munnich, A.; Maroteaux, P. [INSERM, Paris (France)


    The mapping of the achondroplasia locus to the short arm of chromosome 4 and the subsequent identification of a recurrent missense mutation (G380R) in the fibroblast growth factor receptor 3 (FGFR-3) gene has been followed by the detection of common FGFR-3 mutations in two clinically related disorders: thanatophoric dwarfism (types I and II) and hypochondroplasia. The relative clinical homogeneity of achondroplasia was substantiated by demonstration of its genetic homogeneity as more than 98% of all patients hitherto reported exhibit mutations in the transmembrane receptor domain. Although most hypochondroplasia cases were accounted for by a recurrent missense substitution (N540K) in the first tyrosine kinase (TK 1) domain of the receptor, a significant proportion (40%) of our patients did not harbor the N540K mutation and three hypochondroplasia families were not linked to the FGFR-3 locus, thus supporting clinical heterogeneity of this condition. In thanatophoric dwarfism (TD), a recurrent FGFR-3 mutation located in the second tyrosine kinase (TK 2) domain of the receptor was originally detected in 100% of TD II cases; in our series, seven distinct mutations in three different protein domains were identified in 25 of 26 TD I patients, suggesting that TD, like achondroplasia, is a genetically homogenous skeletal disorder. 31 refs., 4 figs., 2 tabs.

  20. ANÁLISIS MUTACIONAL DE LA ACONDROPLASIA EN 20 PACIENTES COLOMBIANOS Mutational analysis of achondroplasia in 20 Colombian patients

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    Ángela Castro


    Full Text Available Antecedentes. La acondroplasia es la más común de las displasias esqueléticas. Se trata de una enfermedad autosómica dominante con penetrancia completa. Esta enfermedad se debe a una mutación en el gen del receptor 3 del factor de crecimiento fibroblástico (FGFR3. El 90% o más de los casos se deben a mutaciones nuevas que se originan en las células germinales de padres sanos, asociada a una edad incrementada. Se ha calculado una frecuencia al nacimiento de 1:10.000 a 1:30.000. En la mayoría de los casos (97% la mutación presente es la transición G1138A, en el dominio transmembranal de gen. En el resto se presenta la transversión en el mismo nucleótido, G1138C. Objetivo. Detectar mutaciones del gen FGFR3 en un grupo de pacientes colombianos con acondroplasia. Material y métodos. Estudiamos un grupo de 20 pacientes con diagnóstico clínico de acondroplasia. Se utilizó el método, ARMS-PCR (Amplification Refractory Mutation System - Polymerase Chain Reaction que emplea dos pares primers diseñados específicamente para amplificar respectivamente los dos diferentes nucleótidos de una mutación puntual. Resultados. 19 pacientes (95%, presentaron la mutación G1138A y un paciente presentó la mutación G1138C (5%. Conclusión. No obstante la acondroplasia presentar un fenotipo considerado distinguible de otras displasias esqueléticas, algunas veces la hipocondroplasia, que se presenta por mutaciones en el mismo gen FGFR3, puede ser difícil de discriminar clínicamente, por lo que el análisis mutacional permite la correcta clasificación, así como de eventualmente otras displasias esqueléticas por mutaciones en otros genes.Background. Achondroplasia is the most common skeletal dysplasia, mainly affecting tubular bones, vertebrae and skull. This is an autosomal dominant syndrome with complete penetrance, due to a mutation in the fibroblast growth factor receptor 3 (FGFR3 gene. Approximately 90% of the achondroplasia cases, are due

  1. Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia (United States)

    Lee, Yi-Ching; Song, I-Wen; Pai, Ya-Ju; Chen, Sheng-De; Chen, Yuan-Tsong


    Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3G380R (FGFR3ACH) cDNA, the most common mutation in human ACH. Heterozygous (FGFR3ACH/+) and homozygous (FGFR3ACH/ACH) mice expressing human FGFR3G380R recapitulate the phenotypes observed in ACH patients, including growth retardation, disproportionate shortening of the limbs, round head, mid-face hypoplasia at birth, and kyphosis progression during postnatal development. We also observed premature fusion of the cranial sutures and low bone density in newborn FGFR3G380R mice. The severity of the disease phenotypes corresponds to the copy number of activated FGFR3G380R, and the phenotypes become more pronounced during postnatal skeletal development. This mouse model offers a tool for assessing potential therapeutic approaches for skeletal dysplasias related to over-activation of human FGFR3, and for further studies of the underlying molecular mechanisms. PMID:28230213

  2. Ser217Cys mutation in the Ig Ⅱ domain of FGFR3 in a Chinese family with autosomal dominant achondroplasia

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    ZHANG Shi-rong; ZHOU Xiao-qing; REN Xiang; WANG Tian-tian; YUAN Ming-xiong; WANG Qing; LIU Jing-yu; LIU Mu-gen


    @@ Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, relative macrocephaly and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. The combined frequency of the disease has been estimated to be 1 in 15 000 live births.1 ACH is inherited in autosomal dominant fashion with a complete penetrance, more than 80% of affected individuals have de novo mutations associated with increased paternal age.

  3. Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation.

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    Zankl, A.; Elakis, G.; Susman, R.D.; Inglis, G.; Gardener, G.; Buckley, M.F.; Roscioli, T.


    We present prenatal and postnatal features of a patient with severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN). Mutation analysis confirmed the clinical diagnosis by detecting the FGFR3 Lys650Met mutation. This case, one of only six with molecular analysis reported in

  4. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta

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    Orioli, I.M. [Universidade Federal do Rio de Janeiro (Brazil); Castilla, E.E. [Centro de Educacion Medica e Investigacion Clinica, Buenos Aires (Argentina); Scarano, G.; Mastroiacovo, P. [Universita Cattolica, Rome (Italy)


    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite (IPIMC) and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congenitas (ECLAMC) series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 {plus_minus} 6.74 years in the IPIMC, and 37.19 {plus_minus} 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 {plus_minus} 7.08 years in the IPIMC, and 36.41 {plus_minus} 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 {plus_minus} 9.25 years, but not in the IPIMC, 32.26 {plus_minus} 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area. 28 refs., 1 fig., 6 tabs.

  5. New evidence for positive selection helps explain the paternal age effect observed in achondroplasia. (United States)

    Shinde, Deepali N; Elmer, Dominik P; Calabrese, Peter; Boulanger, Jérôme; Arnheim, Norman; Tiemann-Boege, Irene


    There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10(-6). We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism.

  6. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. (United States)

    Orioli, I M; Castilla, E E; Scarano, G; Mastroiacovo, P


    The paternal ages of nonfamilial cases of achondroplasia (AC) (n = 78), thanatophoric dysplasia (TD) (n = 64), and osteogenesis imperfecta (OI) (n = 106), were compared with those of matched controls, from an Italian Indagine Policentrica Italiana sulle Malformazioni Congenite and a South American Estudio Colaborativo Latinoamericano de Malformaciones Congénitas series. The degree of paternal age effect on the origin of these dominant mutations differed among the three conditions. Mean paternal age was highly elevated in AC, 36.30 +/- 6.74 years in the IPIMC, and 37.19 +/- 10.53 years in the ECLAMC; less consistently elevated in TD, 33.60 +/- 7.08 years in the IPIMC, and 36.41 +/- 9.38 years in the ECLAMC; and only slightly elevated in OI in the ECLAMC, 31.15 +/- 9.25 years, but not in the IPIMC, 32.26 +/- 6.07 years. Increased maternal age or birth order in these conditions disappeared when corrected for paternal age. Approximately 50% of AC and TD cases, and only 30% of OI cases, were born to fathers above age 35 years. For AC and TD, the increase in relative incidence with paternal age fitted an exponential curve. The variability of paternal age effect in these new mutations could be due, among other reasons, to the high proportion of germ-line mosaicism in OI parents, or to the localization of the AC gene, mapped to the 4p16.3 region, in the neighborhood of an unstable DNA area.

  7. Analysis of callus pattern of tibia lengthening in achondroplasia and a novel method of regeneration assessment using pixel values

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    Singh, Suryaudai; Song, Hae-Ryong; Venkatesh, K.P.; Modi, Hitesh N.; Jang, Ki-Mo; Kim, Seung J. [Korea University Guro Hospital, Rare Diseases Institute, Department of Orthopedic Surgery, Seoul (Korea); Park, Man Sik [Korea University, Department of Biostatistics, College of Medicine, Seoul (Korea)


    To relate morphology of new bone formation to outcome after tibial lengthening performed in patients with achondroplasia. A retrospective analysis of 60 tibial segments in 30 achondroplasia patients was performed. There were 22 female patients and eight male patients, with a mean age of 9.8 years. New bone formation was classified by shape, homogeneity and density. Pixel values in relation to original bone were measured using a picture-archiving communication system (PACS). Clinical outcome was described by the external fixator and maturation indices. Mean lengthening was 9.2 cm (range 3-12.7 cm). The mean external fixator index was 23.4 (range 15.1-50). The mean maturation index was 12.3 days/cm (range 6-40 days/cm). Homogeneous pathways were associated with the best clinical results (fixator index 20.4, maturation index 10.8), followed by heterogeneous pathway (external fixator index 26.5, maturation index 16.8) and radiolucent pathway (fixator index 31.2, maturation index 21.4). Both cylindrical (external fixator index 25.2, maturation index 14.5) and concave (external fixator index 26.6, maturation index 16.3) callus shapes were favourable. Mineralization of new bone became equal to that of normal bone within 16 weeks (mean) for homogeneous pathway, 12 weeks for heterogeneous pathway and 32 weeks for lucent pathway. The type of new bone formation seen on radiographs is related to clinical outcome, with homogeneous pathways being the most favourable ones. (orig.)

  8. A simple and rapid quantitative method of detection of the common achondroplasia mutation: Analysis in mismatch repair deficient cells

    Directory of Open Access Journals (Sweden)

    Grewal Raji


    Full Text Available Achondroplasia is the most common form of dwarfism and has an incidence of approximately 1/7,500. In more than 97% of cases, it is caused by a recurrent point mutation, a G to A substitution at nucleotide position 1138 (G1138A of the fibroblast growth factor receptor 3 gene. Although this is an autosomal dominant condition, more than 90% of all mutations occur sporadically making this one of the most mutagenic sites in the human genome. The reasons for the high spontaneous G1138A mutation rate are not known. This investigation was performed by developing a simple and rapid semi-quantitative allele specific PCR based assay capable of reliably detecting more than 25 mutant G1138A copies in a pool of 300,000 wild type molecules. Using this assay, the G1138A mutation frequency was measured in cell lines deficient in mismatch repair (LoVo, SW48 and comparing it with controls. No differences were found in the frequency of this point mutation between the mismatch repair deficient and wild type cell lines.

  9. Limb lengthening in achondroplasia

    Directory of Open Access Journals (Sweden)

    Sanjay K Chilbule


    Full Text Available Background: Stature lengthening in skeletal dysplasia is a contentious issue. Specific guidelines regarding the age and sequence of surgery, methods and extent of lengthening at each stage are not uniform around the world. Despite the need for multiple surgeries, with their attendant complications, parents demanding stature lengthening are not rare, due to the social bias and psychological effects experienced by these patients. This study describes the outcome and complications of extensive stature lengthening performed at our center. Materials and Methods: Eight achondroplasic and one hypochondroplasic patient underwent bilateral transverse lengthening for tibiae, humeri and femora. Tibia lengthening was carried out using a ring fixator and bifocal corticotomy, while a monolateral pediatric limb reconstruction system with unifocal corticotomy was used for the femur and humerus. Lengthening of each bone segment, height gain, healing index and complications were assessed. Subgroup analysis was carried out to assess the effect of age and bone segment on the healing index. Results: Nine patients aged five to 25 years (mean age 10.2 years underwent limb lengthening procedures for 18 tibiae, 10 femora and 8 humeri. Four patients underwent bilateral lengthening of all three segments. The mean length gain for the tibia, femur and humerus was 15.4 cm (100.7%, 9.9 cm (52.8% and 9.6 cm (77.9%, respectively. Healing index was 25.7, 25.6 and 20.6 days/cm, respectively, for the tibia, femur and humerus. An average of 33.3% height gain was attained. Lengthening of both tibia and femur added to projected height achieved as the 3 rd percentile of standard height in three out of four patients. In all, 33 complications were encountered (0.9 complications per segment. Healing index was not affected by age or bone segment. Conclusion: Extensive limb lengthening (more than 50% over initial length carries significant risk and should be undertaken only after due consideration.

  10. 儿童和青少年软骨发育不全侏儒症双下肢延长术%Bilateral Lengthening of the Lower Limbs in Children and Adolescences with A-chondroplasia

    Institute of Scientific and Technical Information of China (English)

    俞宏亮; 马亮; 赵立登; 席光宝; 劳继军


    1984年6月至1990年12月,采用双侧下肢延长术治疗25例软骨发育不全侏儒患者.男16例,女9例.年龄9~15岁,平均12岁.术前身高平均121cm,术后双侧胫骨骨延长长度为4.5~22cm,平均14.5cm.股骨延长长度为16cm.胫骨骨愈合时间为150~421天,其中24例平均214天获骨愈合.股骨骨愈合时间为180天.%From June 1984 to December 1990,bilateral lenthening of the lower limbs was performed on patients with achondroplasia.Among them,16 were males and 9 females,age 9 to 15 years.The preoperative heights ranged from 100 to 135 cms.The tibial length were increased postoperatively from a minimum of 4.5 cms to a maximum of 22 cms,14.5 cms on average.The ratio between the gained length to the original of the tibia was 25% minimum to 147% maximum,75% on average.The femurs were lengthened by 19 cms on average and made the ratio between the gained length to the original being 88%.Bony union of the lengthened tibia appeared from 150 to 721 days.214 days on average,while the bony union of the femur in 270 days averagely.Comlications included:infection of the pin holes in 6 cases (12 holes),equinus deformity in 8 (16 feet),and delayed union in 1 (bilateral tibiae).There was no neurovascular impairment.

  11. 软骨发育不全家系产前诊断与基因突变分析%Prenatal diagnosis and mutation analysis of fibroblast growth factor receptor 3 gene in achondroplasia

    Institute of Scientific and Technical Information of China (English)

    郝胜菊; 闫有圣; 李静; 郑雷; 张钏; 梁济慈; 陈雪


    Objective To explore the value of prenatal genetical diagnosis by mutation analysis of achondroplasia (ACH) fibroblast growth factor receptor 3 (FGFR3) gene.Methods Genomic DNA from nine ACH patients and their parents in Gansu Maternal and Child Health Hospital from July,2010 to December,2014 was prepared for polymerase chain reaction.Direct sequencing revealed the samples were performed after amplification of exon 10 of FGFR3 containing the potential mutation.Fetal DNA was extracted from cells in both amniotic fluid and umbilical cord,and then exon 10 of FGFR3 was also tested.Three fetuses with short-limb dysplasia were also included and prenatal diagnosis was offered to them through amniocentesis or cordocentesis.Results Prenatal ultrasonography test showed shorter femoral length,which was less than 2-3 standard deviation of normal reference dysplasia fetal performance for femoral short.Femur length is lower than 2-3 standard deviation minus normal value,and discrepancy in biparietal diameter compared with fetuses at the same gestational age.In the four families with one ACH parent,c.1138G > A heterozygous mutation was detected in all of the four mothers,while two fetuses among them showed c.1138G > A heterozygous mutation mutation and the other two were normal.There were other two fetuses with c.1138G > A heterozygous mutation from other two families,one's father had c.1138G > A heterozygous mutations,but not the mother,the other had c.1138G > A heterozygous mutations in both the mother and father.Among the three families with unaffected parents but each had a de novo c.1138G > A mutation child,no mutation of c.1138G > A genotype was detected in their fetuses,neither in the three fetus with short limb dysplasia.Four fetuses with a c.1138G > A mutation and three with short-limb dysplasia were terminated.The other five fetuses whose genotype was normal were born and healthy with normal phenotype at one-year-old follow-up.Conclusion FGFR3 genetic

  12. ANÁLISIS MUTACIONAL DE LA ACONDROPLASIA EN 20 PACIENTES COLOMBIANOS Mutational analysis of achondroplasia in 20 Colombian patients


    Ángela Castro; Andrés Gutiérrez; Luisa Fernanda Rodríguez; Pineda Tatiana; Harvy Velasco; Clara Arteaga; Hugo Sotomayor; Alejandro Giraldo


    Antecedentes. La acondroplasia es la más común de las displasias esqueléticas. Se trata de una enfermedad autosómica dominante con penetrancia completa. Esta enfermedad se debe a una mutación en el gen del receptor 3 del factor de crecimiento fibroblástico (FGFR3). El 90% o más de los casos se deben a mutaciones nuevas que se originan en las células germinales de padres sanos, asociada a una edad incrementada. Se ha calculado una frecuencia al nacimiento de 1:10.000 a 1:30.000. En la mayoría ...

  13. 77 FR 33998 - Make Inoperative Exemptions; Retrofit On-Off Switches for Air Bags (United States)


    ... agency. This regulation is only available for motor vehicles manufactured before September 1, 2012. In..., osteoporosis/arthritis; driver because of achondroplasia; or passenger because of Down syndrome and... vehicles. There have been two confirmed air-bag- related adult fatalities in model year 2004 or...

  14. Veterans Affairs: Health Care and Benefits for Veterans Exposed to Agent Orange (United States)


    pharynx (including tonsils), or nasal cavity (including ears and sinuses); cancers of the pleura, mediastinum, and other unspecified sites within the...1) Achondroplasia; (2) Cleft lip and cleft palate; (3) Congenital heart disease; (4) Congenital talipes equinovarus (clubfoot); (5) Esophageal and

  15. Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene

    DEFF Research Database (Denmark)

    Juul, A; Aksglaede, L; Lund, A M;


    receptor 3 (FGFR3) gene, which is a gain-of-function mutation resulting in achondroplasia. The patient had phenotypic characteristics of achondroplasia (e.g. short limbed dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and repeated semen samples showed sperm concentrations of 0...... a child from a spontaneous pregnancy. The observed testicular size and function in our patient contrast the typical findings in classical Klinefelter syndrome. We speculate that the alteration of FGFR3 protein function in our Klinefelter patient alleviated the destruction of the seminiferous tubules...... and may suggest that the fibroblast growth factor family has a pleiotrophic function in human spermatogonia, which physiologically express FGFR3....

  16. Skeletal dysplasia in ancient Egypt. (United States)

    Kozma, Chahira


    The ancient Egyptian civilization lasted for over 3000 years and ended in 30 BCE. Many aspects of ancient Egyptian culture, including the existence of skeletal dysplasias, and in particular achondroplasia, are well known through the monuments and records that survived until modern times. The hot and dry climate in Egypt allowed for the preservation of bodies and skeletal anomalies. The oldest dwarf skeleton, the Badarian skeleton (4500 BCE), possibly represents an epiphyseal disorder. Among the remains of dwarfs with achondroplasia from ancient Egypt (2686-2190 BCE), exists a skeleton of a pregnant female, believed to have died during delivery with a baby's remains in situ. British museums have partial skeletons of dwarfs with achondroplasia, humeri probably affected with mucopolysaccharidoses, and a skeleton of a child with osteogenesis imperfecta. Skeletal dysplasia is also found among royal remains. The mummy of the pharaoh Siptah (1342-1197 BCE) shows a deformity of the left leg and foot. A mummified fetus, believed to be the daughter of king Tutankhamun, has scoliosis, spina bifida, and Sprengel deformity. In 2006 I reviewed the previously existing knowledge of dwarfism in ancient Egypt. The purpose of this second historical review is to add to that knowledge with an expanded contribution. The artistic documentation of people with skeletal dysplasia from ancient Egypt is plentiful including hundreds of amulets, statues, and drawing on tomb and temple walls. Examination of artistic reliefs provides a glance of the role of people with skeletal dysplasia and the societal attitudes toward them. Both artistic evidence and moral teachings in ancient Egypt reveal wide integration of individuals with disabilities into the society.

  17. Thanatophoric dwarfism. Two case reports and survey of the literature. (United States)

    Nissenbaum, M; Chung, S M; Rosenberg, H K; Buck, B E


    Thanatophoric dwarfism is a severe form of short-limbed dwarfism in which cardiorespiratory failure uniformly results in death in the neonatal period. Its radiographic features include markedly flattened vertebral bodies with a typical U-shaped deformity, a flat squat pelvis, and short, bowed extremities with flaring and irregularity of the metaphyses. These characteristic features distinguish this entity from the two other most commonly confused congenital short-limbed forms of dwarism--achondroplasia and achondrogenesis. The distinctions are discussed in the text.

  18. Selfish spermatogonial selection

    DEFF Research Database (Denmark)

    Lim, Jasmine; Maher, Geoffrey J; Turner, Gareth D H


    The dominant congenital disorders Apert syndrome, achondroplasia and multiple endocrine neoplasia-caused by specific missense mutations in the FGFR2, FGFR3 and RET proteins respectively-represent classical examples of paternal age-effect mutation, a class that arises at particularly high...... frequencies in the sperm of older men. Previous analyses of DNA from randomly selected cadaveric testes showed that the levels of the corresponding FGFR2, FGFR3 and RET mutations exhibit very uneven spatial distributions, with localised hotspots surrounded by large mutation-negative areas. These studies imply...

  19. Pediatric aspects of skeletal dysplasia. (United States)

    Ozono, Keiichi; Namba, Noriyuki; Kubota, Takuo; Kitaoka, Taichi; Miura, Kohji; Ohata, Yasuhisa; Fujiwara, Makoto; Miyoshi, Yoko; Michigami, Toshimi


    Skeletal dysplasia is a disorder of skeletal development characterized by abnormality in shape, length, a number and mineral density of the bone. Skeletal dysplasia is often associated with manifestation of other organs such as lung, brain and sensory systems. Skeletal dysplasias or dysostosis are classified with more than 400 different names. Enchondral bone formation is a coordinated event of chondrocyte proliferation, differentiation and exchange of terminally maturated chondrocyte with bone. Impaired enchondral bone formation will lead to skeletal dysplasia, especially associated with short long bones. Appropriate bone volume and mineral density are achieved by balance of bone formation and bone resorption and mineralization. The gene encoding fibroblast growth factor receptor 3 is responsible for achondroplasia, representative skeletal dysplasia with short stature. The treatment with growth hormone is approved for achondroplasia in Japan. Osteogenesis imperfecta is characterized by low bone mineral density and fragile bone. Data on the beneficial effect of bisphosphonate for osteogenesis imperfecta are accumulating. Osteopetrosis has high bone mineral density, but sometimes show bone fragility. In Japan as well as other countries, pediatrician treat larger numbers of patients with skeletal dysplasia with short stature and fragile bones compared to 20 years ago.

  20. Advances on circulating fetal DNA in maternal plasma

    Institute of Scientific and Technical Information of China (English)

    FU Xian-hu; CHEN Han-ping


    @@ The discovery of cell-free fetal DNA in maternal plasma in 1997 has opened up new possibilities for noninvasive diagnosis.1 By RT-PCR, circulating fetal DNA can be detected in the plasma of pregnant women,even in the first trimester of pregnancy,2,3 and thus can be used for noninvasive prenatal diagnosis of sex-linked disorders,4-6 the RhD status of fetuses,7 and single gene disorders such as beta-thalassaemia,8,9 congenital adrenal hyperplasia,10 and achondroplasia.11 In addition,quantitative aberrations of circulating fetal DNA may indicate various pregnancy-associated disorders,including1 Preeclampsia,12-14 preterm labor15,16 and fetal trisomy 21.17

  1. Perceval S aortic valve implantation in an achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Nikolaos G Baikoussis


    Full Text Available Despite cardiovascular disease in patients with dwarfism is not rare; there is a lack of reports referring to cardiac interventions in such patients. Dwarfism may be due to achondroplasia or hormonal growth disorders. We present a 58-year-old woman with episodes of dyspnea for several months. She underwent on transthoracic echocardiography, and she diagnosed with severe aortic valve stenosis. She referred to our department for surgical treatment of this finding. In accordance of her anthropometric characteristics and her very small aortic annulus, we had the dilemma of prosthesis selection. We decided to implant a stentless valve to optimize her effective orifice area. Our aim is to present the successful Perceval S valve implantation and the descriptions of the problems coming across in operating on these special patients. To our knowledge, this is the first case patient in which a Perceval S valve is implanted according to the international bibliography.

  2. Livebirth prevalence and follow-up of malformation syndromes in 27,472 newborns. (United States)

    Higurashi, M; Oda, M; Iijima, K; Iijima, S; Takeshita, T; Watanabe, N; Yoneyama, K


    The results of a survey of the birth prevalence of congenital anomalies among 27,472 consecutive newborn babies at a large maternity hospital in Tokyo are reported. There were 29 cases with trisomy-21; 5 cases with trisomy-13 syndrome; 5 with trisomy-18 syndrome; 2 with cri-du-chat syndrome; and one each with partial monosomy 4p, partial trisomy 5p, partial trisomy 6p, partial trisomy 9p, partial trisomy 9q, partial monosomy 10p, and partial monosomy 13q. Single cases of the following were observed: the Hallermann-Streiff syndrome, the Treacher-Collins syndrome, achondroplasia, arthrogryposis, the Beckwith-Wiedemann syndrome, the asplenia syndrome, the Klippel-Trenaunay-Weber syndrome, the Marfan syndrome, the Carpenter syndrome, the Goldenhar syndrome, and the Pierre Robin syndrome. The results of follow-ups to determine the life-prognosis of each patient with an autosomal aberration are reported.

  3. Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutations. (United States)

    Wilkie, Andrew O M


    The discovery in 1994 that highly specific mutations of fibroblast growth factor (FGF) receptor 3 caused the most common form of human short-limbed dwarfism, achondroplasia, heralded a new era in FGF receptor (FGFR) biology. A decade later, the purpose of this review is to survey how the study of humans with FGFR mutations continues to provide insights into FGFR function in health and disease, and the clinical applications of these findings. Amongst the most interesting recent discoveries have been the description of novel phenotypes associated with FGFR1 and FGFR3 mutations; identification of fundamental differences in the cellular mechanisms of mutant FGFR2 and FGFR3 action; and the direct identification of FGFR2 and FGFR3 mutations in sperm. These clinical observations illustrate the pleiotropism of FGFR action and fuel ongoing efforts to understand the rich biology and pathophysiology of the FGF signalling system.

  4. Acute obstructive hydrocephalus complicating decompression surgery of the craniovertebral junction (United States)

    Ohya, Junichi; Chikuda, Hirotaka; Nakatomi, Hirofumi; Sakamoto, Ryuji; Saito, Nobuhito; Tanaka, Sakae


    Obstructive hydrocephalus has been described as a rare complication following foramen magnum decompression for Chiari malformation. However, there are few reports of obstructive hydrocephalus after spinal surgery for other pathologies of the craniovertebral junction (CVJ). The authors herein report a 52-year-old female with achondroplasia presenting with an 8-month history of myelopathy due to spinal cord compression at CVJ. She underwent resection of the C1 posterior arch and part of the edge of the occipital bone. A computed tomography (CT) scan obtained 1-week after the surgery revealed bilateral infratentorial fluid collection. The patient was first managed conservatively; however, on the 17th day, her consciousness level showed sudden deterioration. Emergency CT demonstrated marked hydrocephalus due to obstruction of the cerebral aqueduct. Acute obstructive hydrocephalus can occur late after decompression surgery at the CVJ, and thus should be included in the differential diagnosis of a deteriorating mental status. PMID:27366268

  5. Germline Stem Cell Competition, Mutation Hot Spots, Genetic Disorders, and Older Fathers. (United States)

    Arnheim, Norman; Calabrese, Peter


    Some de novo human mutations arise at frequencies far exceeding the genome average mutation rate. Examples include the common mutations at one or a few sites in the genes that cause achondroplasia, Apert syndrome, multiple endocrine neoplasia type 2B, and Noonan syndrome. These mutations are recurrent, provide a gain of function, are paternally derived, and are more likely to be transmitted as the father ages. Recent experiments have tested whether the high mutation frequencies are due to an elevated mutation rate per cell division, as expected, or to an advantage of the mutant spermatogonial stem cells over wild-type stem cells. The evidence, which includes the surprising discovery of testis mutation clusters, rules out the former model but not the latter. We propose how the mutations might alter spermatogonial stem cell function and discuss how germline selection contributes to the paternal age effect, the human mutational load, and adaptive evolution.

  6. Lumbar gibbus in storage diseases and bone dysplasias

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Berdon, W.E. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Lachman, R.S. [International Skeletal Dysplasia Registry, Los Angeles, CA (United States); Anyane-Yeboa, K. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Ruzal-Shapiro, C. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Roye, D.P. Jr. [Department of Orthopedic Surgery, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States)


    Objective. The objective of this study was to review the problem of lumbar gibbus in children with storage diseases and bone dysplasias utilizing plain films and MR imaging. Materials and methods. Clinical histories and radiographic images in five patients with storage diseases [four mucopolysaccharidosis (MPS) and one mucolipidosis] and two with achondroplasia were reviewed. The International Skeletal Dysplasia Registry (Los Angeles, Calif.), surveyed for all patients with lumbar gibbus and skeletal dysplasias, provided 12 additional cases. Results. All patients had localized gibbus of the upper lumbar spine, characterized by anterior wedging and posterior displacement of the vertebrae at the apex of the curve, producing a beaked appearance. The curve, exaggerated in the sitting or standing position, was most severe in the two patients with MPS-IV (one of whom died). Both developed severe neurologic signs and symptoms requiring surgical intervention. In four patients, MR images demonstrated the apex of the curve to be at or below the conus. Two patients demonstrated anterior herniation of the intervertebral discs at the apex of the curve, though the signal intensity of the intervertebral discs was normal. Conclusion. Lumbar gibbus has important neurologic and orthopedic implications, and is most severe in patients with MPS. The etiology of the gibbus with vertebral beaking is multifactorial and includes poor truncal muscle tone, weight-bearing forces, growth disturbance and anterior disc herniation. The curve is generally at or below the conus. Neurologic complications are unusual, although orthopedic problems can arise. Due to their longer survival, patients with achondroplasia or Morquio`s disease are more vulnerable to eventual gibbus-related musculoskeletal complications. (orig.). With 6 figs., 2 tabs.

  7. Pseudoachondroplasia: A case report

    Directory of Open Access Journals (Sweden)

    Radlović Vladimir


    Full Text Available Introduction. Pseudoachondroplasia (PSACH is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. Case Outline. A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm, achondroplasia-like rhizomelic dwarfism recognized by the absence of abnormality at birth, normal craniofacial appearance, characteristic epiphyseal and metaphyseal radiographic finding and joint hyperlaxity.

  8. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type

    Energy Technology Data Exchange (ETDEWEB)

    Tueysuez, Beyhan [Istanbul University, Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul (Turkey); Gazioglu, Nurperi [Istanbul University, Department of Neurosurgery, Cerrahpasa Medical School, Istanbul (Turkey); Uenguer, Savas [Istanbul University, Department of Pediatric Radiology, Cerrahpasa Medical School, Istanbul (Turkey); Aji, Dolly Yafet [Istanbul University, Department of Pediatrics, Cerrahpasa Medical School, Istanbul (Turkey); Tuerkmen, Seval [Istanbul University, Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul (Turkey); Universitatsklinikum Berlin, Charite Virchow-Klinik, Berlin (Germany)


    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. (orig.)

  9. Pneumomediastinum, Subcutaneous Emphysema, and Tracheal Tear in the Early Postoperative Period of Spinal Surgery in a Paraplegic Achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Sinan Kahraman


    Full Text Available Achondroplasia was first described in 1878 and is the most common form of human skeletal dysplasia. Spinal manifestations include thoracolumbar kyphosis, foramen magnum, and spinal stenosis. Progressive kyphosis can result in spinal cord compression and paraplegia due to the reduced size of spinal canal. The deficits are typically progressive, presenting as an insidious onset of paresthesia, followed by the inability to walk and then by urinary incontinence. Paraplegia can be the result of direct pressure on the cord by bone or the injury to the anterior spinal vessels by a protruding bone. Surgical treatment consists of posterior instrumentation, fusion with total wide laminectomy at stenosis levels, and anterior interbody support. Pedicle screws are preferred for spinal instrumentation because wires and hooks may induce spinal cord injury due to the narrow spinal canal. Pedicle lengths are significantly shorter, and 20–25 mm long screws are appropriate for lower thoracic and lumbar pedicles in adult achondroplastic There is no information about the appropriate length of screws for the upper thoracic pedicles. Tracheal injury due to inappropriate pedicle screw length is a rare complication. We report an extremely rare case of tracheal tear due to posterior instrumentation and its management in the early postoperative period.

  10. All Madelung deformities are not endocrine

    Directory of Open Access Journals (Sweden)

    Ajay Kumar


    Full Text Available Madelung deformity is a rare inherited disorder associated with endocrine disorders like Turner′s syndrome, pseudohypoparathyroidism, but can be seen with short stature homeobox deficiency conditions such as Leri-Weill dyschondrosteosis (LWD and Langers mesomelic dysplasia. It has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis (MPS and achondroplasia. Madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna. A 13-year-old girl was referred to us for evaluation of bilateral deformity of wrist and short stature. There was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness. On X-ray, wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of Madelung deformity. X-ray spine was normal. Ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone. Luteinizing hormone was normal and so was urine MPS screening. Based on the above points the diagnosis of LWD was made.

  11. Anatomic Considerations for Radical Retropubic Prostatectomy in an Achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Dennis Gyomber


    Full Text Available This is the first report of a radical retropubic prostatectomy (RRP in an achondroplastic dwarf. We highlight the pelvic anatomy, precluding laparoscopic or robotic prostatectomy, and making open surgery extremely difficult. We review relevant literature regarding general, urological, and orthopedic abnormalities of achondroplasia (ACH and present a clinical case. No reports of RRP in achondroplastic dwarfs exist, with only one case of an abandoned RRP due to similar pelvic anatomy in a patient with osteogenesis imperfecta. Significant lumbar lordosis found in ACH results in a short anteroposterior dimension, severely limiting access to the prostate. We present a case of a 62-year-old achondroplastic dwarf who had Gleason 3+4 disease on transrectal ultrasound-guided biopsy in four from 12 cores. Surgery was difficult due to narrow anteroposterior pelvic dimension, but achievable. Histological analysis revealed multifocal prostate cancer, with negative surgical margins and no extraprostatic extension. RRP in ACH patients, although possible, should be approached with caution due to the abnormal pelvic dimensions, and discussions regarding potential abandonment of surgery should be included during informed consent. This case highlights the preoperative use of computed tomography to assist in the surgical planning for patients with difficult pelvic anatomy.

  12. Multikinase activity of fibroblast growth factor receptor (FGFR) inhibitors SU5402, PD173074, AZD1480, AZD4547 and BGJ398 compromises the use of small chemicals targeting FGFR catalytic activity for therapy of short-stature syndromes. (United States)

    Gudernova, Iva; Vesela, Iva; Balek, Lukas; Buchtova, Marcela; Dosedelova, Hana; Kunova, Michaela; Pivnicka, Jakub; Jelinkova, Iva; Roubalova, Lucie; Kozubik, Alois; Krejci, Pavel


    Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) cause the most common genetic form of human dwarfism, achondroplasia (ACH). Small chemical inhibitors of FGFR tyrosine kinase activity are considered to be viable option for treating ACH, but little experimental evidence supports this claim. We evaluated five FGFR tyrosine kinase inhibitors (TKIs) (SU5402, PD173074, AZD1480, AZD4547 and BGJ398) for their activity against FGFR signaling in chondrocytes. All five TKIs strongly inhibited FGFR activation in cultured chondrocytes and limb rudiment cultures, completely relieving FGFR-mediated inhibition of chondrocyte proliferation and maturation. In contrast, TKI treatment of newborn mice did not improve skeletal growth and had lethal toxic effects on the liver, lungs and kidneys. In cell-free kinase assays as well as in vitro and in vivo cell assays, none of the tested TKIs demonstrated selectivity for FGFR3 over three other FGFR tyrosine kinases. In addition, the TKIs exhibited significant off-target activity when screened against a panel of 14 unrelated tyrosine kinases. This was most extensive in SU5402 and AZD1480, which inhibited DDR2, IGF1R, FLT3, TRKA, FLT4, ABL and JAK3 with efficiencies similar to or greater than those for FGFR. Low target specificity and toxicity of FGFR TKIs thus compromise their use for treatment of ACH. Conceptually, different avenues of therapeutic FGFR3 targeting should be investigated.

  13. Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders. (United States)

    Wojtal, Daria; Kemaladewi, Dwi U; Malam, Zeenat; Abdullah, Sarah; Wong, Tatianna W Y; Hyatt, Elzbieta; Baghestani, Zahra; Pereira, Sergio; Stavropoulos, James; Mouly, Vincent; Mamchaoui, Kamel; Muntoni, Francesco; Voit, Thomas; Gonorazky, Hernan D; Dowling, James J; Wilson, Michael D; Mendoza-Londono, Roberto; Ivakine, Evgueni A; Cohn, Ronald D


    Clustered regularly interspaced short palindromic repeat (CRISPR) has arisen as a frontrunner for efficient genome engineering. However, the potentially broad therapeutic implications are largely unexplored. Here, to investigate the therapeutic potential of CRISPR/Cas9 in a diverse set of genetic disorders, we establish a pipeline that uses readily obtainable cells from affected individuals. We show that an adapted version of CRISPR/Cas9 increases the amount of utrophin, a known disease modifier in Duchenne muscular dystrophy (DMD). Furthermore, we demonstrate preferential elimination of the dominant-negative FGFR3 c.1138G>A allele in fibroblasts of an individual affected by achondroplasia. Using a previously undescribed approach involving single guide RNA, we successfully removed large genome rearrangement in primary cells of an individual with an X chromosome duplication including MECP2. Moreover, removal of a duplication of DMD exons 18-30 in myotubes of an individual affected by DMD produced full-length dystrophin. Our findings establish the far-reaching therapeutic utility of CRISPR/Cas9, which can be tailored to target numerous inherited disorders.

  14. Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association?

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    Manal Mustafa


    Full Text Available FGFR3 mutations cause wide spectrum of disorders ranging from skeletal dysplasias (hypochondroplasia, achondroplasia, and thanatophoric dysplasia, benign skin tumors (epidermal nevi, seborrhaeic keratosis, and acanthosis nigricans, and epithelial malignancies (multiple myeloma and prostate and bladder carcinoma. Hypochondroplasia is the most common type of short-limb dwarfism in children resulting from fibroblast growth factor receptor 3 (FGFR3 mutation. Acanthosis nigricans might be seen in severe skeletal dysplasia, including thanatophoric dysplasia and SADDAN syndrome, without a biochemical evidence of hyperinsulinemia. Insulin insensitivity and acanthosis nigricans are uncommonly seen in hypochondroplasia patients with FGFR3 mutations which may represent a new association. We aim to describe the association of hypochondroplasia, acanthosis nigricans, and insulin resistance in a child harboring FGFR3 mutation. To our knowledge, this is the first case report associating the p.N540 with acanthosis nigricans and the second to describe hyperinsulinemia in hypochondroplasia. This finding demonstrates the possible coexistence of insulin insensitivity and acanthosis nigricans in hypochondroplasia patients.

  15. The acrophysis: a unifying concept for understanding enchondral bone growth and its disorders. II. Abnormal growth

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    Oestreich, Alan E. [Department of Radiology, Cincinnati Children' s Hospital Medical Center, 3333 Burnet Avenue, OH 45229-3039, Cincinnati (United States)


    In order to discuss and illustrate the effects common to normal and abnormal enchondral bone at the physes and at all other growth plates of the developing child, the term ''acrophysis'' was proposed. Acrophyses include the growth plates of secondary growth centers including carpals and tarsals and apophyses, and the growth plates at the nonphyseal ends of small tubular bones. Abnormalities at acrophyseal sites are analogous to those at the physeal growth plates and their metaphyses. For example, changes relating to the zone of provisional calcification (ZPC) are often important to the demonstration of such similarities. Lead lines were an early example of the concept of analogy from abnormality due to physeal and to acrophyseal disturbance. The ZPC is a key factor in understanding patterns of rickets and its healing. Examples (including hypothyroidism, scurvy and other osteoporosis, Ollier disease, achondroplasia, and osteopetrosis, as well as the family of frostbite, Kashin-Beck disease, and rat bite fever) illustrate the acrophysis principle and in turn their manifestations are explained by that principle. (orig.)

  16. Atlantoaxial subluxation. Radiography and magnetic resonance imaging correlated to myelopathy

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    Yamashita, Y.; Takahashi, M.; Sakamoto, Y.; Kojima, R.

    Twenty-nine patients with atlantoaxial subluxation (18 with rheumatoid arthritis, 2 due to trauma, 4 with os odontoideum, and one each with polyarteritis nodosa, rheumatic fever, Klippel-Feil syndrome, achondroplasia, and cause unknown) were evaluated using a 0.22 tesla resistive MRI unit. Cord compression was classified into four grades according to the degree on magnetic resonance imaging. There were 7 patients with no thecal sac compression (grade 0), 10 with a minimal degree of subarachnoid space compression without cord compression (grade 1), 7 with mild cord compression (grade 2), and 5 with severe cord compression or cord atrophy (grade 3). Although the severity of myelopathy showed poor correlation with the atlantodental interval on conventional radiography, high correlation was observed between MR grading and the degree of myelopathy. The high signal intensity foci were observed in 7 or 12 patients with cord compression (grades 2 and 3) on T2 weighted images. Other frequently observed findings in rheumatoid arthritis included soft tissue masses of low to intermediate signal intensity in the paraodontoid space, erosions of the odontoid processes, and atlanto-axial impaction on T1 and T2 weighted images.

  17. Paleodysmorphology and paleoteratology: Diagnosing and interpreting congenital conditions of the skeleton in anthropological contexts. (United States)

    Oostra, Roelof-Jan; Boer, Lucas; van der Merwe, Alie E


    Most congenital conditions have low prevalence, but collectively they occur in a few percent of all live births. Congenital conditions are rarely encountered in anthropological studies, not least because many of them have no obvious effect on the skeleton. Here, we discuss two groups of congenital conditions that specifically affect the skeleton, either qualitatively or quantitatively. Skeletal dysplasias (osteochondrodysplasias) interfere with the histological formation, growth and maturation of skeletal tissues leading to diminished postural length, but the building plan of the body is unaffected. Well- known skeletal dysplasias represented in the archeological record include osteogenesis imperfecta and achondroplasia. Dysostoses, in contrast, interfere with the building plan of the body, leading to e.g. missing or extraskeletal elements, but the histology of the skeletal tissues is unaffected. Dysostoses can concern the extremities (e.g., oligodactyly and polydactyly), the vertebral column (e.g., homeotic and meristic anomalies), or the craniofacial region. Conditions pertaining to the cranial sutures, i.e., craniosynostoses, can be either skeletal dysplasias or dysostoses. Congenital conditions that are not harmful to the individual are known as anatomical variations, several of which have a high and population-specific prevalence that could potentially make them useful for determining ethnic origins. In individual cases, specific congenital conditions could be determinative in establishing identity, provided that ante-mortem registration of those conditions was ensured. Clin. Anat. 29:878-891, 2016. © 2016 The Authors Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.

  18. A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice

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    Roe Bruce A


    Full Text Available Abstract Background The long bone abnormality (lbab mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. Results A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents. Conclusion A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.

  19. Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. (United States)

    Goriely, Anne; Wilkie, Andrew O M


    Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term "paternal age effect" (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time-explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition.

  20. A systematic review of genetic skeletal disorders reported in Chinese biomedical journals between 1978 and 2012

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    Cui Yazhou


    Full Text Available Abstract Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs in China. This study systematically reviewed GSDs as defined in “Nosology and Classification of genetic skeletal disorders (2010 version” using Chinese biomedical literature published over the past 34 years from 1978 to 2012. In total, 16,099 GSDs have been reported. The most frequently reported disorders were Marfan syndrome, osteogenesis imperfecta, fibrous dysplasia, mucopolysaccharidosis, multiple cartilaginous exostoses, neurofibromatosis type 1 (NF1, osteopetrosis, achondroplasia, enchondromatosis (Ollier, and osteopoikilosis, accounting for 76.5% (12,312 cases of the total cases. Five groups (group 8, 12, 14, 18, 21 defined by “Nosology and Classification of genetic skeletal disorders” have not been reported in the Chinese biomedical literature. Gene mutation testing was performed in only a minor portion of the 16,099 cases of GSDs (187 cases, 1.16%. In total, 37 genes for 41 different GSDs were reported in Chinese biomedical literature, including 43 novel mutations. This review revealed a significant imbalance in rare disease identification in terms of geographic regions and hospital levels, suggesting the need to create a national multi-level network to meet the specific challenge of care for rare diseases in China.

  1. Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders

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    Taha Faruqi


    Full Text Available A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

  2. Fibroblast growth factor (FGF) signaling in development and skeletal diseases. (United States)

    Teven, Chad M; Farina, Evan M; Rivas, Jane; Reid, Russell R


    Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

  3. Ellis-van Creveld syndrome associated with chronic intestinal pseudo-obstruction. (United States)

    Iwakura, Hideo; Fujii, Katsunori; Furutani, Yoshiyuki; Takatani, Tomozumi; Ebata, Ryota; Nakanishi, Toshio; Mitsunaga, Tetsuya; Saito, Takeshi; Kishimoto, Takashi; Yoshida, Hideo; Shimojo, Naoki


    Ellis-van Creveld (EVC) syndrome is a rare autosomal recessive disorder characterized by hypoplastic nails, polydactyly, and achondroplasia. Patients usually exhibit normal cognitive function and no remarkable developmental delay. We herein present an unusual case of EVC syndrome. A Japanese 2-year-old boy was born at term, but immediately developed severe respiratory failure due to thorax deformity, postaxial polydactyly and nail hypoplasia. We identified a novel pattern of germinal compound heterozygous nonsense EVC2 mutations of c.1814C > A (p. S605X) and c.2653C > T (p. R885X), leading to the diagnosis of EVC syndrome. Interestingly, he also had severe developmental delay, and suddenly developed excessive abdominal distension at the age of 2. On surgery, extensive necrotic bowel with chronic intestinal pseudo-obstruction was noted. This is, to our knowledge, a most severe phenotype of EVC syndrome, illustrating that the specific pattern of EVC2 compound heterozygous mutations may cause severe developmental delay and intestinal malfunction.

  4. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type. (United States)

    Tüysüz, Beyhan; Gazioğlu, Nurperi; Ungür, Savaş; Aji, Dolly Yafet; Türkmen, Seval


    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered.

  5. Complex oncologic reconstruction of a mandibular and floor of mouth defect with a fibula free flap in an achondroplastic patient. (United States)

    García-Rozado, Alvaro; Martín Sastre, Roberto J; López Cedrún, José L


    The fibular free flap is seen as one of the foremost technical options in mandibular reconstruction, especially in those defects where long bone is required. Cases with squamous-cell carcinoma of the floor of the mouth with mandibular spread and subsequent segmentary mandibular removal are the cornerstone examples. A case of squamous-cell carcinoma of the whole floor of the mouth with mandibular invasion is reported. Radical resection of the floor of the mouth and bilateral mandibular horizontal ramus was performed, with a bony defect extending from angle to angle. The patient revealed an achondroplastic condition, with remarkable dwarfism and long-bone morphological alterations, that minimized the potential fibular length to transfer. A microsurgical reconstruction with an osteocutaneous fibular free flap was undertaken. The flap design was technically compromised by the forward bowing of the fibula and the ossification of the interosseous membrane. Specific intraoperative strategies for dealing with anatomic variations are discussed. The fibular free flap is an excellent technique for mandibular reconstruction. Morphological deviations can modify the design of the flap. Achondroplasia is not a deterrent in successful use of the free fibula flap for reconstruction of the head and neck in adequately selected cases.

  6. Genetic drift. The ancient Egyptian dwarfs of the pyramids: the high official and the female worker. (United States)

    Kozma, Chahira; Sarry El Din, Azza Mohamed; El Shafy El Banna, Rokia Abd; El Samie Kandeel, Wafaa Abd; Lachman, Ralph


    The existence of dwarfism is amply documented in ancient Egypt due to the rich biological and artistic legacies. In previous articles published in this journal, I discussed the roles of people with skeletal dysplasia in ancient Egyptian civilization. In this article I, along with my Egyptian and American colleagues, describe two skeletons of dwarfs that date to 2700-2184 BCE and were unearthed from a funerary complex near the Great Pyramids in Giza. The first skeleton belongs to a high official, Per-ni-ankh-w, who died between 45 and 50 years of age. His statue is on display in the Egyptian Museum of Cairo. The second skeleton belongs to a pregnant female worker found with a fetus in situ. Her estimated age at death was 25-30 years. She most likely died during childbirth due to a small pelvic outlet as supported by her narrow sacrum. The fetal bones appear normal. Radiological examination of both skeletons confirmed the clinical diagnosis of achondroplasia. Ancient Egyptians concerned themselves with the search for spiritual fulfillment through the tradition of moral teachings. Amenemope, a wise man who lived during the reign of Amenhotep III (1391-1354 BCE), advocated respect toward individuals with disabilities: Do not jeer at a blind man nor tease a dwarf, Neither interfere with the condition of a cripple. Do not taunt a man who is in the hand of God, Nor scowl at him if he errs. In summary, artistic, biological, and written resources indicate that dwarfs were well integrated in ancient Egyptian society.

  7. Thyroid hormones regulate fibroblast growth factor receptor signaling during chondrogenesis. (United States)

    Barnard, Joanna C; Williams, Allan J; Rabier, Bénédicte; Chassande, Olivier; Samarut, Jacques; Cheng, Sheue-Yann; Bassett, J H Duncan; Williams, Graham R


    Childhood hypothyroidism causes growth arrest with delayed ossification and growth-plate dysgenesis, whereas thyrotoxicosis accelerates ossification and growth. Thyroid hormone (T(3)) regulates chondrocyte proliferation and is essential for hypertrophic differentiation. Fibroblast growth factors (FGFs) are also important regulators of chondrocyte proliferation and differentiation, and activating mutations of FGF receptor-3 (FGFR3) cause achondroplasia. We investigated the hypothesis that T(3) regulates chondrogenesis via FGFR3 in ATDC5 cells, which undergo a defined program of chondrogenesis. ATDC5 cells expressed two FGFR1, four FGFR2, and one FGFR3 mRNA splice variants throughout chondrogenesis, and expression of each isoform was stimulated by T(3) during the first 6-12 d of culture, when T(3) inhibited proliferation by 50%. FGFR3 expression was also increased in cells treated with T(3) for 21 d, when T(3) induced an earlier onset of hypertrophic differentiation and collagen X expression. FGFR3 expression was reduced in growth plates from T(3) receptor alpha-null mice, which exhibit skeletal hypothyroidism, but was increased in T(3) receptor beta(PV/PV) mice, which display skeletal thyrotoxicosis. These findings indicate that FGFR3 is a T(3)-target gene in chondrocytes. In further experiments, T(3) enhanced FGF2 and FGF18 activation of the MAPK-signaling pathway but inhibited their activation of signal transducer and activator of transcription-1. FGF9 did not activate MAPK or signal transducer and activator of transcription-1 pathways in the absence or presence of T(3). Thus, T(3) exerted differing effects on FGFR activation during chondrogenesis depending on which FGF ligand stimulated the FGFR and which downstream signaling pathway was activated. These studies identify novel interactions between T(3) and FGFs that regulate chondrocyte proliferation and differentiation during chondrogenesis.

  8. Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia

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    Schmidt Martin


    Full Text Available Abstract Background Understanding the pathogenesis of the chiari-like malformation in the Cavalier King Charles Spaniel (CKCS is incomplete, and current hypotheses do not fully explain the development of syringomyelia (SM in the spinal cords of affected dogs. This study investigates an unconventional pathogenetic theory for the development of cerebrospinal fluid (CSF pressure waves in the subarachnoid space in CKCS with SM, by analogy with human diseases. In children with achondroplasia the shortening of the skull base can lead to a narrowing of the jugular foramina (JF between the cranial base synchondroses. This in turn has been reported to cause a congestion of the major venous outflow tracts of the skull and consequently to an increase in the intracranial pressure (ICP. Amongst brachycephalic dog breeds the CKCS has been identified as having an extremely short and wide braincase. A stenosis of the JF and a consequential vascular compromise in this opening could contribute to venous hypertension, raising ICP and causing CSF jets in the spinal subarachnoid space of the CKCS. In this study, JF volumes in CKCSs with and without SM were compared to assess a possible role of this pathologic mechanism in the development of SM in this breed. Results Computed tomography (CT scans of 40 CKCSs > 4 years of age were used to create three-dimensional (3D models of the skull and the JF. Weight matched groups (7–10 kg of 20 CKCSs with SM and 20 CKCSs without SM were compared. CKCSs without SM presented significantly larger JF -volumes (median left JF: 0.0633 cm3; median right JF: 0.0703 cm3; p 3; median right JF: 0.0434 cm3; p Conclusion A stenosis of the JF and consecutive venous congestion may explain the aetiology of CSF pressure waves in the subarachnoid space, independent of cerebellar herniation, as an additional pathogenetic factor for the development of SM in this breed.

  9. Dwarfs in ancient Egypt. (United States)

    Kozma, Chahira


    Ancient Egypt was one of the most advanced and productive civilizations in antiquity, spanning 3000 years before the "Christian" era. Ancient Egyptians built colossal temples and magnificent tombs to honor their gods and religious leaders. Their hieroglyphic language, system of organization, and recording of events give contemporary researchers insights into their daily activities. Based on the record left by their art, the ancient Egyptians documented the presence of dwarfs in almost every facet of life. Due to the hot dry climate and natural and artificial mummification, Egypt is a major source of information on achondroplasia in the old world. The remains of dwarfs are abundant and include complete and partial skeletons. Dwarfs were employed as personal attendants, animal tenders, jewelers, and entertainers. Several high-ranking dwarfs especially from the Old Kingdom (2700-2190 BCE) achieved important status and had lavish burial places close to the pyramids. Their costly tombs in the royal cemeteries and the inscriptions on their statutes indicate their high-ranking position in Egyptian society and their close relation to the king. Some of them were Seneb, Pereniankh, Khnumhotpe, and Djeder. There were at least two dwarf gods, Ptah and Bes. The god Ptah was associated with regeneration and rejuvenation. The god Bes was a protector of sexuality, childbirth, women, and children. He was a favored deity particularly during the Greco-Roman period. His temple was recently excavated in the Baharia oasis in the middle of Egypt. The burial sites and artistic sources provide glimpses of the positions of dwarfs in daily life in ancient Egypt. Dwarfs were accepted in ancient Egypt; their recorded daily activities suggest assimilation into daily life, and their disorder was not shown as a physical handicap. Wisdom writings and moral teachings in ancient Egypt commanded respect for dwarfs and other individuals with disabilities.

  10. Cellular evidence for selfish spermatogonial selection in aged human testes. (United States)

    Maher, G J; Goriely, A; Wilkie, A O M


    Owing to a recent trend for delayed paternity, the genomic integrity of spermatozoa of older men has become a focus of increased interest. Older fathers are at higher risk for their children to be born with several monogenic conditions collectively termed paternal age effect (PAE) disorders, which include achondroplasia, Apert syndrome and Costello syndrome. These disorders are caused by specific mutations originating almost exclusively from the male germline, in genes encoding components of the tyrosine kinase receptor/RAS/MAPK signalling pathway. These particular mutations, occurring randomly during mitotic divisions of spermatogonial stem cells (SSCs), are predicted to confer a selective/growth advantage on the mutant SSC. This selective advantage leads to a clonal expansion of the mutant cells over time, which generates mutant spermatozoa at levels significantly above the background mutation rate. This phenomenon, termed selfish spermatogonial selection, is likely to occur in all men. In rare cases, probably because of additional mutational events, selfish spermatogonial selection may lead to spermatocytic seminoma. The studies that initially predicted the clonal nature of selfish spermatogonial selection were based on DNA analysis, rather than the visualization of mutant clones in intact testes. In a recent study that aimed to identify these clones directly, we stained serial sections of fixed testes for expression of melanoma antigen family A4 (MAGEA4), a marker of spermatogonia. A subset of seminiferous tubules with an appearance and distribution compatible with the predicted mutant clones were identified. In these tubules, termed 'immunopositive tubules', there is an increased density of spermatogonia positive for markers related to selfish selection (FGFR3) and SSC self-renewal (phosphorylated AKT). Here we detail the properties of the immunopositive tubules and how they relate to the predicted mutant clones, as well as discussing the utility of

  11. New insight on FGFR3-related chondrodysplasias molecular physiopathology revealed by human chondrocyte gene expression profiling.

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    Laurent Schibler

    Full Text Available Endochondral ossification is the process by which the appendicular skeleton, facial bones, vertebrae and medial clavicles are formed and relies on the tight control of chondrocyte maturation. Fibroblast growth factor receptor (FGFR3 plays a role in bone development and maintenance and belongs to a family of proteins which differ in their ligand affinities and tissue distribution. Activating mutations of the FGFR3 gene lead to craniosynostosis and multiple types of skeletal dysplasia with varying degrees of severity: thanatophoric dysplasia (TD, achondroplasia and hypochondroplasia. Despite progress in the characterization of FGFR3-mediated regulation of cartilage development, many aspects remain unclear. The aim and the novelty of our study was to examine whole gene expression differences occurring in primary human chondrocytes isolated from normal cartilage or pathological cartilage from TD-affected fetuses, using Affymetrix technology. The phenotype of the primary cells was confirmed by the high expression of chondrocytic markers. Altered expression of genes associated with many cellular processes was observed, including cell growth and proliferation, cell cycle, cell adhesion, cell motility, metabolic pathways, signal transduction, cell cycle process and cell signaling. Most of the cell cycle process genes were down-regulated and consisted of genes involved in cell cycle progression, DNA biosynthesis, spindle dynamics and cytokinesis. About eight percent of all modulated genes were found to impact extracellular matrix (ECM structure and turnover, especially glycosaminoglycan (GAG and proteoglycan biosynthesis and sulfation. Altogether, the gene expression analyses provide new insight into the consequences of FGFR3 mutations in cell cycle regulation, onset of pre-hypertrophic differentiation and concomitant metabolism changes. Moreover, impaired motility and ECM properties may also provide clues about growth plate disorganization. These

  12. Prevalence of dominant mutations in Spain: effect of changes in maternal age distribution. (United States)

    Martínez-Frías, M L; Herranz, I; Salvador, J; Prieto, L; Ramos-Arroyo, M A; Rodríguez-Pinilla, E; Cordero, J F


    We studied the birth prevalence of autosomal dominant mutations in Spain and estimated how a decrease in maternal age distribution may lead to reduction in dominant mutations. The data were collected by the Estudio Colaborativo Español de Malformaciones Congénitas from April, 1976, to December, 1985. Among 553,270 liveborn infants monitored during the period, 66 infants with autosomal dominant conditions were identified. These included Apert, Crouzon, Hay-Wells, Treacher-Collins, Robinow, Stickler, Adams-Oliver, and the blepharophimosis syndromes, achondroplasia, cleidocranial dysostosis, and thanatophoric dysplasia. The overall rate of autosomal dominant conditions was 1.2 per 10,000 liveborn infants. Thirteen (20%) had an affected relative, and 52 (79%) had a negative family history. One case was excluded because of insufficient family data. The rate of autosomal dominant mutations was 0.9 per 10,000 liveborn infants, or 47 per 1 million gametes. A reduction in the maternal age distribution of mothers age 35 years and older from the current 10.8% to 4.9%, as in Atlanta, Georgia, would reduce the rate of Down syndrome in Spain by 33% and through a change in parternal age distribution may lead to a reduction in dominant mutations of about 9.6%. This suggests that a public health campaign to reduce older maternal age distribution in Spain may also lead to a reduction in dominant mutations and emphasizes the potential that a direct campaign for fathers to complete their families before age 35 years may have a small, but measurable, effect in the primary prevention of dominant mutations.

  13. Anestesia em anã acondroplásica obesa mórbida para gastroplastia redutora Anestesia en enana acondroplásica obesa mórbida para gastroplastia reductora Anesthesia for bariatric surgery in an achondroplastic dwarf with morbid obesity

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    Maria Angélica Abrão


    í la conducción de la anestesia.BACKGROUND AND OBJECTIVES: Achondroplasia is the most common form among the different types of osteochondrodysplasia that cause dwarfism. Dwarves develop obesity quite frequently, and surgical treatment has shown greater efficacy, both for effective weight loss and long term maintenance. The objective of this report was to present the case of bariatric surgery with Y-en-Roux gastric bypass in an achondroplastic dwarf with morbid obesity. The different difficulties in the anesthetic management of this patient and the way they were dealt with were discussed in order to decrease intraoperative morbidity and mortality. CASE REPORT: This is a 29 years old female dwarf with achondroplasia and morbid obesity since childhood. She was 123 cm tall and weighed 144 kg at the time of admission to the Bariatric Surgery service. With a body mass index (BMI of 95.18 kg.m-2, she had several associated diseases especially of the respiratory system and osteoarticular system. After a long follow-up with diet, exercises, and psychological support, her clinical condition improved and she was referred for surgery: Y-en-Roux gastroplasty using the technique of Capella-Fobi. Intubation of the awake patient under direct laryngoscopy was difficult and a bronchofibroscope had to be used. Surgery was uneventful and the patient was maintained under total intravenous anesthesia with continuous infusion of remifentanil and propofol. She was extubated at the end of the surgery still in the operating room. CONCLUSIONS: The simultaneous comorbidities of achondroplasia and morbid obesity can hinder the anesthetic management, especially regarding the airways. A thorough pre-anesthetic evaluation is necessary to anticipate the conducts and minimize risks, therefore optimizing the evolution of anesthesia.

  14. Prenatal craniofacial development: new insights on normal and abnormal mechanisms. (United States)

    Johnston, M C; Bronsky, P T


    multifactorial etiology. Genetic variations in TGF alpha s, RAR alpha s, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzon's syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis. Poorly co-ordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws), by regulatory genes should do much to explain the very frequent "mismatches" found in malocclusions and other dentofacial "deformities". Future directions for research, including possibilities for prevention, are discussed.

  15. Fibroblast growth factor expression in the postnatal growth plate. (United States)

    Lazarus, Jacob E; Hegde, Anita; Andrade, Anenisia C; Nilsson, Ola; Baron, Jeffrey


    Fibroblast growth factor (FGF) signaling is essential for endochondral bone formation. Mutations cause skeletal dysplasias including achondroplasia, the most common human skeletal dysplasia. Most previous work in this area has focused on embryonic chondrogenesis. To explore the role of FGF signaling in the postnatal growth plate, we quantitated expression of FGFs and FGF receptors (FGFRs) and examined both their spatial and temporal regulation. Toward this aim, rat proximal tibial growth plates and surrounding tissues were microdissected, and specific mRNAs were quantitated by real-time RT-PCR. To assess the FGF system without bias, we first screened for expression of all known FGFs and major FGFR isoforms. Perichondrium expressed FGFs 1, 2, 6, 7, 9, and 18 and, at lower levels, FGFs 21 and 22. Growth plate expressed FGFs 2, 7, 18, and 22. Perichondrial expression was generally greater than growth plate expression, supporting the concept that perichondrial FGFs regulate growth plate chondrogenesis. Nevertheless, FGFs synthesized by growth plate chondrocytes may be physiologically important because of their proximity to target receptors. In growth plate, we found expression of FGFRs 1, 2, and 3, primarily, but not exclusively, the c isoforms. FGFRs 1 and 3, thought to negatively regulate chondrogenesis, were expressed at greater levels and at later stages of chondrocyte differentiation, with FGFR1 upregulated in the hypertrophic zone and FGFR3 upregulated in both proliferative and hypertrophic zones. In contrast, FGFRs 2 and 4, putative positive regulators, were expressed at earlier stages of differentiation, with FGFR2 upregulated in the resting zone and FGFR4 in the resting and proliferative zones. FGFRL1, a presumed decoy receptor, was expressed in the resting zone. With increasing age and decreasing growth velocity, FGFR2 and 4 expression was downregulated in proliferative zone. Perichondrial FGF1, FGF7, FGF18, and FGF22 were upregulated. In summary, we have

  16. 胎儿肢骨发育异常18例产前诊断%Prenatal diagnose of abnormalities of fetal limb bone

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    宋晶; 王欣


    Objective To discuss the prenatal diagnosis of abnormalities of fetal limb bone.Methods We selected 18 cases which long bone of fetus less than 2SD of average volume of gestational weeks or long bone changed into angle or other fetus's abnormalities by first B-mode ultrasonic. All above cases was delivered at Capital Medical University of Obstetric and Gynecological Hospital during Jan. 2006 to Dec. 2009. We B-mode ultrasonic was used to measure fetus's biparietal diameter (BPD) ,femur length (FL) ,abdominal circumference(AC) ,head circumference(HC) ,humerus length (HL) ,amniotic fluid index (AFI) and structures of organ and calculated FL/AC, growth speed of long bone. The standard of achondroplasia is that FL and HL are less than 4SD of average of gestational weeks or FL/AC less than 0. 16. The standard of Osteogenesis Imperfecta is fetal long bone of fetus shows short and thick, curves into angle, fracture in uterus by X-ray, or skull shows thin or sink by X-ray. Results (1) By B-mode ultrasonic and X-ray exam of all 18 cases: 7 cases shows that HC >2SD, 10 cases shows too much amniotic fluid, 12 cases shows AFI > 18.0, 9 cases shows abnormalities of narrow cavitas thoracis, disordered vertebral column, or unusual architecture of heart. For cases 1 to 14 are achondroplasia, among which,11 cases are FL<4SD and HL<4SD, 2 cases are FL <3SD and HL <4SD, 1 case is not only FL <2SD and HL <3SD but also hydroncus all over the body of fetus. The growth velocity of long bone of fetus in all the 14 cases is more slowly than the normal rate. For all the above 14 cases, 12 cases FL/AC <0. 16, 1 case FL/AC =0. 19, 1 case FL/AC =0. 20. The length of femur or humerus is shorter than the normal rate and have other abnormalities the above last two cases. For case 15 and 16, they don't show any abnormalities of bone growth though one year's follow up studying. For case 17 and 18, they are osteogenesis imperfecta. (2) The result of fetal perinatal period fate and

  17. Seqüestro pulmonar extralobar: análise anatomopatológica de dois casos em natimortos e revisão da literatura Extralobar pulmonary sequestration: anatomical analysis of two cases in stillbirths and review of literature

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    Ítalo Martins de Oliveira


    Full Text Available O seqüestro pulmonar é definido como uma massa anormal de tecido pulmonar sem comunicação com a árvore brônquica. É anomalia rara, responsável por 0,15-6,45% das malformações pulmonares congênitas. Quando possui revestimento pleural próprio, chama-se seqüestro pulmonar extralobar (SPE. Este trabalho descreve dois casos de SPE em natimortos (NM com 32 (1 e 34 (2 semanas de gestação com diagnóstico clínico de hipoxia intra-uterina e adenomatose cística, respectivamente, e faz revisão da literatura. O diagnóstico envolveu análise ultra-sonográfica, sindrômica, macroscópica e microscópica dos NM. Foi observada massa supradiafragmática no hemitórax esquerdo ligada à aorta torácica (1 e ao diafragma (2. As MFs associadas foram agenesia tímica (2, hipoplasia pulmonar (2, pé torto congênito (1 e acondroplasia de membros (2. A microscopia evidenciou, nos dois casos, tecido pulmonar imaturo e pedículo vascularizado e inervado.Pulmonary sequestration represents an abnormal pulmonary mass that does not communicate with the tracheobronchial tree. It is a rare malformation (MF, accountable for 0.15%-6.45% of pulmonary congenital MFs. When it has its own pleural covering, it is called extralobar (EBPS. This work describes two cases of EBPS in stillbirths (SB, at 32 (1 and 34 (2 weeks' gestation, with clinical diagnosis of intrauterine hypoxia and cystic adenomatosis, respectively. It also reviews the literature on the subject. The diagnosis involved ultrasonographic, syndromic, macroscopic and microscopic analysis. The macroscopy showed a supradiaphragmatic mass in the left hemithorax linked to thoracic aorta (1 and diaphragm (2. The associated MFs were: thymic agenesis (2, pulmonary hypoplasia (2, clubfoot (1 and achondroplasia (2. Microscopy demonstrated, in both cases, immature pulmonary tissue and vascularized and innervated pedicle.

  18. From Horus the child to Hephaestus who limps: a romp through history. (United States)

    Aterman, K


    The question of why Hephaestus, the Greek god of smiths, limped has been the subject of much debate, mainly on mythological grounds. This debate extended also into the field of medical diagnosis, with attempts at defining the nature of the deformity that made the crippled Hephaestus the buffoon of the other Olympic gods. One problem encountered in these debates was the changes to which the ugly young Hephaestus was subjected with the passing of time-from a limping deformed youth to the later dignified and normal man. While some authors, largely influenced by poetic Greek texts and vase paintings, attributed the limp to talipes (club-feet), others pointed to certain features suggestive of achondroplasia. Since the image of the early Hephaestus is based mainly on the much earlier concept of the Egyptian god Ptah, who as the triune god of the resurrection sometimes is depicted as an achondroplastic dwarf (Ptah-Pataikos), the suggestion of the possible achondroplastic dwarf-like nature of the early Hephaestus is not implausible. It is supported by similarities in the image of Hephaestus to some features in other Egyptian gods, such as the domestic god Bes, the guardian of the new-born, and the Horus the Child or Harpocrates (Greek), yet another protector of youth and "the symbol of everything that is young and vigorous" [Budge, 1969: The Gods of the Egyptians, or Studies in Egyptian Mythology. Volume I.]. The characteristic feature of this child-god is the "lock of Harpocrates" on the right side of his head. That this lock can sometimes also be seen not only on the head of Ptah-Pataikos and of Bes but also on the young Hephaestus is highly suggestive of the Egyptian influence on his image. Recently, however, another interesting explanation of Hephaestus's limp has been suggested that may explain why the Egyptian influenced image of the early achondroplastic Hephaestus changed to the later, more Grecian view of the smith-god who hobbled because of club

  19. Estudo comparativo do nível de qualidade de vida entre sujeitos acondroplásicos e não-acondroplásicos Comparative study of quality of life level between achondroplasics and non-achondroplasics subjects

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    Mariana Pereira Cervan


    Full Text Available A acondroplasia é caracterizada como um distúrbio genético autossômico dominante que afeta a ossificação endocondral, constituindo uma das causas de nanismo. Entre as características está presente principalmente a baixa estatura e desproporção tronco/membros. Diante disso, o acondroplásico poderá se mostrar inferiorizado e insatisfeito com sua aparência física, influenciando, juntamente a outros fatores, na qualidade de vida (QV dessa população. OBJETIVO: Comparar o nível de QV entre sujeitos acondroplásicos e não-acondroplásicos. MÉTODO: Foram avaliados 21 indivíduos acondroplásicos, sendo nove homens e 13 mulheres, pareados por idade e gênero, a 21 não-acondroplásicos. O nível de QV foi estimado por meio do questionário WHOQOL-BREF. RESULTADOS: Na comparação entre sujeitos acondroplásicos e não acondroplásicos do gênero feminino constatou-se que no domínio físico as mulheres acondroplásicas apresentaram escore médio significativamente menor, enquanto na comparação entre os gêneros, o grupo de mulheres acondroplásicas apresentou escore médio significativamente menor que os homens acondroplásicos no domínio psicológico. CONCLUSÃO: No presente estudo, a QV não apresentou diferença entre os grupos, entretanto, nos domínios físico e psicológico, as mulheres acondroplásicas demonstraram menor satisfação com sua condição.Achondroplasia is characterized as an autosomal dominant genetic disturbance which affects the endochondral ossification which is a common cause of dwarfism syndrome. Among the characteristics the most common are the short stature and disproportional trunk/limbs. Thus, the achondroplasic subjects can face themselves inferior and not satisfied with their physical appearance, influencing, among other factors, the quality of life of this population. OBJECTIVE: To compare the quality of life level between achondroplasic and non-achondroplasic subjects. METHODS: Study with 21


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    Mukhergee G. S


    Full Text Available BACKGROUND Spinal stenosis is one of the most common conditions in the elderly. It is defined as a narrowing of the spinal canal. The term stenosis is derived from the Greek word for narrow, which is “Stenos”. The first description of this condition is attributed to Antoine portal in 1803. Verbiest is credited with coining the term spinal stenosis and the associated narrowing of the spinal canal as its potential cause. [1-10] Kirkaldy–Willis subsequently described the degenerative cascade in the lumbar spine as the cause for the altered anatomy and pathophysiology in spinal stenosis. [11-15] If compression does not occur, the canal should be described as narrow but not stenotic. Some studies defined lumbar spinal stenosis as a “narrowing of the osteoligamentous vertebral canal and/or the intervertebral foramina causing compression of the thecal sac and/or the caudal nerve roots; at a single vertebral level, narrowing may affect the whole canal or part of it” (Postacchini 1983. This definition distinguished between disc herniation and stenosis. [16] . The most common type of spinal stenosis is caused by degenerative arthritis of the spine. Hypertrophy and ossification of the posterior longitudinal ligament which usually are confined to the cervical spine, and diffuse idiopathic skeletal hyperostosis (DISH syndrome also may result in an acquired form of spinal stenosis. Congenital forms caused by disorders such as achondroplasia and dysplastic spondylolisthesis are much less common. Congenital spinal stenosis usually is central and is evident or imaging studies. Idiopathic congenital narrowing usually involves the anteroposterior dimension of the canal secondary to short pedicles; the patient otherwise is normal. In contrast, in achondroplasia, the canal is narrowed in the anteroposterior plane owing to shortened pedicles and in lateral dimension because of diminished interpedicular distance. Acquired forms of spinal stenosis usually are

  1. Bloqueio bilateral do nervo pudendo para hemorroidectomia em paciente acondroplásico: relato de caso Bloqueo bilateral del nervio pudendo para hemorroidectomía en paciente acondroplásico: relato de caso Bilateral blockade of the pudend nerve to hemorrhoidectomy in achondroplasic patient: case report

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    Bruno Salomé de Morais


    ética espontánea. La anestesia de esos pacientes presenta varias particularidades. El objetivo del presente relato fue el de describir un caso de paciente acondroplásico, con previo historial de intervención quirúrgica de la columna para descompresión medular, sometido a Hemorroidectomía a través de bloqueo bilateral de los nervios pudendos. RELATO DEL CASO: Paciente del sexo masculino, 47 años, acondroplásico, que fue ingresado para la realización de hemorroidectomía.Al hacérsele el examen físico presentaba el cuello acortado con extensión limitada de la cabeza, Mallampati clase IV, distancia tireomentoniana de 6 cm y abertura de la boca de 3,5 cm. La columna vertebral presentaba cifosis torácica y lordosis lumbar acentuada, además de cicatriz quirúrgica en la región lumbar. Fue realizado el bloqueo bilateral de los nervios pudendos con ropivacaina a 1%, por vía transperineal, con una aguja aislada de 0,8 mm x 100 mm 21G (Stimuplex A100 BBraun, Melsungen, Germany conectada al estimulador de nervios periféricos (Stimuplex-DIG, BBraun.El paciente fue colocado en decúbito ventral y la cirugía iniciada después de 15 minutos da administración del anestésico. Durante todo el procedimiento, el paciente permaneció consciente y no relató ningún dolor o incomodidad. Hasta el momento del alta hospitalaria (22h después de la realización del bloqueo, el paciente no refirió dolor, incomodidad, náusea, vómito, bloqueo motor, retención o incontinencia urinaria. Después del alta, evolucionó bien presentando evacuación después de 31 horas de efectuada la cirugía. CONCLUSIONES: El caso mostró el uso del bloqueo bilateral de los nervios pudendos, con el auxilio del neuroestimulador como técnica anestésica aislada para la hemorroidectomía.BACKGROUND AND OBJECTIVES: The achondroplasic dwarfism or achondroplasia is the most common form of dwarfism and occurs, in most of the cases, as a result of spontaneous genetic alteration. The anesthesia in these