Craniofacial-Deafness-Hand Syndrome

Clinical Characteristics
Ocular Features: 

This rare syndrome has anomalies in periocular structures but not in the eye itself.  The lid fissures are downward slanting with telecanthus and hypertelorism.  The nasolacrimal duct was missing in several individuals.

Systemic Features: 

The midface is generally flat with underdeveloped maxillary bones and absent or small nasal bones but there may be frontal bossing.  The nose appears hypoplastic with a broad, flat root resulting in dystopia canthorum.  Micrognathia and a high arched palate are sometimes present.   The sinuses are often underdeveloped.  There may be ulnar deviation of the hands and fingers while flexion contractures and clinodactyly of the 5th finger are often present.  A sensorineural hearing loss is present in many individuals.  No poliosis has been reported.

Genetics

This is an autosomal dominant condition secondary to mutations in the PAX3 gene (22q36.1) in at least some patients.  Changes in the same gene are responsible for types 1 and 3 of the Waardenburg syndrome (193500, 148820).  In fact, the major mutation, a heterozygous C-to-G transversion, has been identified in the same codon in both CDHS and Waardenburg 3 (148820) patients.

More patients need to be genotyped to clarify the clinical features distinctive of Waardenburg types 1 and 3 (193500, 148820) and CDHS syndrome.  Should we consider these conditions allelic or simply the result of variable expressivity?  The appearance of the nasal root and associated structures is similar and both conditions are associated with sensorineural hearing loss.  Type 3 Waardenburg syndrome (148820) often has a cleft palate and musculoskeletal deformities of the upper limbs and fingers.  So far, no pigmentation changes have been reported in CDHS.

Treatment
Treatment Options: 

Surgical release of contractures could be considered.

References
Article Title: 

References

Gad A, Laurino M, Maravilla KR, Matsushita M, Raskind WH. Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome? Am J Med Genet A. 2008 Jul 15;146A(14):1880-5.

PubMedID: 18553554

Asher JH Jr, Sommer A, Morell R, Friedman TB. Missense mutation in the paired domain of PAX3 causes craniofacial-deafness-hand syndrome. Hum Mutat. 1996;7(1):30-5.

PubMedID: 8664898