The presence of cardiovascular abnormalities in patients with spontaneous cerebrospinal fluid (CSF) leaks are not well-documented in the literature, as cardiovascular evaluation is not generally ...pursued if a patient does not exhibit additional clinical features suggesting an inherited connective tissue disorder. We aimed to assess this association, enrolling a consecutive group of 50 patients referred for spinal CSF leak consultation. Through echocardiographic evaluation and detailed medical history, we estimate that up to 20 % of patients presenting with a spontaneous CSF leak may have some type of cardiovascular abnormality. Further, the increase in prevalence of aortic dilatation in our cohort was statistically significant in comparison to the estimated population prevalence. This supports a clinical basis for echocardiographic screening of these individuals for cardiovascular manifestations that may have otherwise gone unnoticed or evolved into a more severe manifestation.
Fibroblast growth factor receptor 3 (FGFR3) is the only gene known to cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TD I and TD II). A second, as ...yet unidentified, gene also causes HCH. In this study, we used sequencing analysis to determine the frequency of FGFR3 mutations for each phenotype in 324 cases from the International Skeletal Dysplasia Registry (ISDR). Our data suggest that there is a considerable overlap of genotype and phenotype between ACH and HCH. Thus, it is important to test for mutations found in either disorder when ACH or HCH is suspected. Only two of 29 cases with HCH did not have an identified mutation in FGFR3, much less than previously reported. We recommend testing other mutations in FGFR3, instead of just the common HCH mutation, p.Asn540Lys. The mutation frequency for TD I and TD II in the largest series of cases to date are also reported. This study provides valuable information on FGFR3 mutation frequency of four skeletal dysplasias for clinical diagnostic laboratories and clinicians.
Based on the largest number of skeletal dysplasia cases, this study provides valuable information on Fibroblast growth factor receptor 3 (FGFR3) mutation frequency of four skeletal dysplasias for clinical diagnostic laboratories and clinicians.
Israeli investigators have identified several relatively frequent disorders due to founder point mutations in Persian (Iranian) Jews, who, for nearly three centuries up to the Islamic Revolution of ...1979, were completely isolated reproductively.
Using a community-based model previously employed with Tay-Sachs disease prevention, we developed a pilot program for the Persian Jewish community of greater Los Angeles. We screened for mutations responsible for four relatively frequent autosomal recessive conditions in Persian Jews in which effective interventions are available for each: Pseudocholinesterase deficiency (butyryl cholinesterase deficiency); Congenital hypoaldosteronism (corticosterone methyl oxidase II); Autoimmune polyendocrinopathy (autoimmune regulatory element); and Hereditary Inclusion Body myopathy.
One thousand individuals volunteered. Mutations were assessed in saliva-derived DNA and were positive for 121/1000 butyryl cholinesterase deficiency; 92/1000 Hereditary Inclusion Body myopathy; 38/1000 corticosterone methyl oxidase II; and 37/1000 autoimmune regulatory element. Ten homozygous individuals (9 butyryl cholinesterase deficiency and 1 Hereditary Inclusion Body myopathy) and 10 “at-risk” couples (seven for butyryl cholinesterase deficiency and one each for the other three disorders) were identified. These frequencies are comparable with those in Israel and indicate an extraordinary level of inbreeding, as anticipated.
A carefully planned effort can be delivered to an “increased risk” community if detailed attention is given to planning and organization. However, availability of an effective intervention for those found to be “at-risk” or possibly affected, is essential before embarking.
Abstract Objective Cortical hyperostosis is a bone disease that may, at times, occur with a prenatal onset. This study seeks to present the characteristic patterns of prenatal-onset cortical ...hyperostosis (PCH) with regard to the radiographic features, and tries to ascertain whether PCH is a separate entity from infantile cortical hyperostosis (ICH), known as classic Caffey Disease. Materials and methods This retrospective study identified cases with PCH based upon abnormal radiographic and chondro-osseous morphological and clinical findings, as available, from the International Skeletal Dysplasia Registry between 1987 and 2009. Outcomes and clinical information were also identified from medical records. Results Based upon radiographic results, we found 20 individuals with PCH, of whom 10 neonatally survived, and 10 died. Hyperostosis of the mandible was found in 18/20, and of the skull base in 16/20 cases. Hyperostosis of the ribs was found in 17/20 cases, of the scapulae in 14/20, and of the clavicles in 4/20. Hyperostosis of the ileum was found in 11/20 cases, and of the long bones in all 20/20 cases, of which three cases had fibula sparing. No hyperostosis of the hands, feet, and spine was found. Conclusions Our results suggest that, based upon clinical features and radiographic expression, ICH and PCH represent two separate entities, and that ICH should continue to be referred to as Caffey Disease and that PCH should be called Caffey Dysplasia. The findings of symmetrical hyperostosis of the mandible, ribs, scapulae, ilea, and long bones in any combination should suggest the diagnosis of PCH.
Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common ...among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated.
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