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.

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Keywords CHARGE syndrome, CHD7, Congenital lower limb deformities, Congenital upper limb deformities
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Journal American Journal of Medical Genetics. Part A
van de Laar, I.M.B.H, Dooijes, D, Hoefsloot, E.H, Simon, M, Hoogeboom, J, & Devriendt, K. (2007). Limb anomalies in patients with CHARGE syndrome: An expansion of the phenotype. American Journal of Medical Genetics. Part A, 143(22), 2712–2715. doi:10.1002/ajmg.a.32008