Xq26.3 microdeletion in a male with wildervanck syndrome

Background: Wildervanck Syndrome (WS; cervico-oculo-acoustic syndrome) consists of Duane retraction syndrome (DRS), the Klippel-Feil anomaly, and congenital deafness. It is much more common in females than males and could be due to an X-linked mutation that is lethal to hemizygous males. We present the genetic evaluation of a male with WS and his family. Materials and Methods: Clinical evaluation and neuroimaging, sequencing of candidate genes, and array comparative genomic hybridization. Results: The patient had bilateral type 1 DRS, fusion of almost the entire cervical spine, and bilateral severe sensorineural hearing loss due to bilateral cochlear dysplasia; he also had congenital heart disease requiring surgery. His parents were unrelated, and he had eight unaffected siblings. The patient had no mutation found by Sanger sequencing of HOXA1, KIF21A, SALL4, and CHN1. He had a 3kB deletion in the X-chromosome at Xq26.3 that was not found in his mother, one unaffected sibling, or 56 healthy controls of matching ethnicity. This deletion encompassed only one gene, Fibroblast Growth Factor Homologous Factor 13 (FGF13), which encodes a 216-amino acid protein that acts intracellularly in neurons throughout brain development. Conclusions: Analysis of this patient's phenotype and genotype open the possibility that X-chromosome deletions may be a cause of WS with larger deletions being lethal to males and that FGF13 mutations may be a cause of WS.