title: Limb anomalies in patients with CHARGE syndrome: an expansion of the phenotype.
abstract: CHARGE syndrome is characterized by a wide clinical variability. During the past years the phenotypic spectrum was markedly expanded. Limb anomalies were initially not recognized as part of the phenotype but more recently mild limb anomalies were described in approximately 30% of the patients. We report on three patients with several major features of CHARGE syndrome who, in addition, presented severe limb anomalies including monodactyly, tibia aplasia, and bifid femora. Three different heterozygous truncating mutations in the CHD7 gene were detected. It has been hypothesized before that the CHARGE syndrome is caused by a disruption of mesenchymal-epithelial interaction. Given the expression of the CHD7 gene in the developing limb bud, it was anticipated that limb defects would belong to the spectrum of manifestations of CHARGE syndrome. The present observations provide further support to this hypothesis.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. i.vandelaar@erasmusmc.nl
authors.forename: Ingrid
authors.initials: I
authors.lastname: Van de Laar
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.forename: Lies
authors.initials: L
authors.lastname: Hoefsloot
authors.forename: Marleen
authors.initials: M
authors.lastname: Simon
authors.forename: Jeanette
authors.initials: J
authors.lastname: Hoogeboom
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
mesh_terms: D000328:Adult; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D013577:Syndrome
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human