Search results for "Limb Deformities"
showing 10 items of 10 documents
Second study on the recurrence risk of isolated esophageal atresia with or without trachea-esophageal fistula among first-degree relatives: no eviden…
2013
BACKGROUND Esophageal atresia with/without trachea-esophageal fistula (EA/TEF) denotes a spectrum of severe congenital malformations. The aim of this systematic study was to determine both the recurrence risk for EA/TEF, and the risk for malformations of the VATER/VACTERL association spectrum, in first-degree relatives of patients with isolated EA/TEF. METHODS A total of 108 unrelated patients with isolated EA/TEF were included. These individuals had 410 first-degree relatives including 194 siblings. The presence of EA/TEF and malformations of the VATER/VACTERL association spectrum in relatives was systematically assessed. Data from the EUROCAT network were used for comparison. RESULTS None…
Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III
2000
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated p…
Yunis-Varón Syndrome Is Caused by Mutations in FIG4, Encoding a Phosphoinositide Phosphatase
2013
Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of FIG4 in affected individuals from three unrelated families. FIG4 encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P(2) levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of Fig4-null mouse fibroblasts. Homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarg…
De novo 13q deletions in two patients with mild anorectal malformations as part of VATER/VACTERL and VATER/VACTERL-like association and analysis of E…
2013
Item does not contain fulltext Anorectal malformations (ARMs) comprise a broad spectrum of conditions ranging from mild anal anomalies to complex cloacal malformations. In 40-50% of cases, ARM occurs within the context of defined genetic syndromes or complex multiple congenital anomalies, such as VATER/VACTERL (vertebral defects [V], ARMs [A], cardiac defects [C], tracheoesophageal fistula with or without esophageal atresia [TE], renal malformations [R], and limb defects [L]) association. Here, we report the identification of deletions at chromosome 13q using single nucleotide polymorphism-based array analysis in two patients with mild ARM as part of VATER/VACTERL and VATER/VACTERL-like ass…
Esophageal atresia in newborns: a wide spectrum from the isolated forms to a full VACTERL phenotype?
2013
Background: VATER association was first described in 1972 by Quan and Smith as an acronym which identifies a non-random co-occurrence of Vertebral anomalies, Anal atresia, Tracheoesophageal fistula and/or Esophageal atresia, Radial dysplasia. It is even possible to find out Cardiovascular, Renal and Limb anomalies and the acronym VACTERL was adopted, also, embodying Vascular, as single umbilical artery, and external genitalia anomalies. Methods: Data on patients with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) admitted in the Neonatal Intensive Care Unit (NICU) between January 2003 and January 2013 were evaluated for the contingent occurrence of typical VACTERL a…
Genetic syndrome suspicion: examples of clinical approach in the neonatal unit.
2010
Overgrowth syndromes: the practical clinical approach. Excessive growth can be present in a variety of medical conditions as result of abnormal fetal metabolism (i.e., maternal gestational diabetes) or of an overgrowth syndrome. Within this latter group of diseases, a LGA newborn requires a complex differential diagnosis encompassing several syndromes, such as Beckwith-Wiedemman, Sotos, Weaver, Simpson-Golabi-Behmel, Perlman, and Bannayan-Riley-Ruvalcaba. Partial or global overgrowth, other dysmorphisms, abdominal organs anomalies, as well as benign and malignant tumors are the common issues to examine for the diagnosis and the monitoring of all these disorders. The molecular bases of these…
WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome
2018
International audience; Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. All current known pathogenic variants reside in genes within the noncanonical Wnt signaling pathway including ROR2, WNT5A, and more recently, DVL1 and DVL3. However, ∼70% of autosomal-dominant Robinow syndrome cases remain molecularly unsolved. To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like pheno…
Haploinsufficiency of the NOTCH1 receptor as a cause of Adams-Oliver syndrome with variable cardiac anomalies
2015
Background— Adams–Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. Methods and Results— Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregat…
Etiological heterogeneity and clinical variability in newborns with esophageal atresia
2018
Abstract Background The aim of this study was to define different characteristics of infants with esophageal atresia and correlations with neonatal level of care, morbidity and mortality occurring during hospital stay. Methods Charts of all newborns with esophageal atresia (EA) admitted to our University NICU between January 2003 and November 2016 were reviewed and subdivided in four groups related to different clinical presentations; EA as an isolated form (A), with a concomitant single malformation (B), as VACTERL association (C), and in the context of a syndrome or an entity of multiple congenital anomalies (D). Results We recruited 67 infants with EA (with or without tracheoesophageal f…
Chondrodysplasia punctata, tibia-metacarpal (MT) type.
1990
We describe 7 patients with a new form of chondrodysplasia punctata. Its principal clinical manifestations are flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn infant are discrete calcific stippling, coronal clefts of vertebral bodies, short tibiae, and shortness of the 2nd and 3rd metacarpal bones. Radiologic findings in the older child include shortness of tibiae and the 3rd and 4th metacarpals.