Wildervanck Syndrome

Clinical Features

The Wildervanck syndrome consists of congenital perceptive deafness, Klippel-Feil anomaly (see 118100), and abducens palsy with retractio bulbi (Duane syndrome). The disorder is limited, or almost completely limited, to females, raising the question of sex-linked dominance with lethality in the hemizygous male. This syndrome (at least profound childhood deafness and Klippel-Feil malformation) may be responsible for at least 1% of deafness among females. The deafness is perceptive and has been shown by radiologic studies to be due to a bony malformation of the inner ear. Kirkham (1969) described a family which was affected through 5 generations with perceptive deafness and in which 2 members had Duane syndrome. Konigsmark and Gorlin (1976) favored multifactorial inheritance. Wildervanck (1978) gave an extensive review of the subject and concluded that polygenic inheritance with limitation to females is most likely.

Balci et al. (2002) reported a child with Wildervanck syndrome with the following findings on MRI: diastematomyelia of the lower medulla and cervical cord accompanied by vermian hypoplasia, tonsillar herniation, and resulting triventricular hydrocephalus. The authors suggested that children with Wildervanck syndrome should be investigated for craniospinal abnormalities by MRI.

Abu-Amero et al. (2014) described a male with Wildervanck syndrome who had a microdeletion in the X chromosome. The patient had bilateral type 1 Duane retraction syndrome, type 1 Klippel-Feil anomaly causing almost complete fusion of the cervical vertebral bodies, and bilateral deafness with inner ear malformations involving the cochlea, vestibules, and semicircular canals. Neuroimaging revealed malformations of the lower brainstem and cervical spinal cord with incomplete diastematomyelia, as reported by Balci et al. (2002). In addition, the patient had ventricular septal defect and an atrial septal defect requiring surgery at age 2.5 years.

Cytogenetics

In a male patient with Wildervanck syndrome, Abu-Amero et al. (2014) detected an approximately 3-kb deletion in chromosome Xq26.3 (chrX:137,779,548-137,782,146, NCBI35) using array CGH. The deletion encompassed the FGF13 gene (300070). The deletion was not present in the patient's mother or in 1 of 8 unaffected sibs. The father was deceased but was reported to have been free of phenotypic features seen in the son.