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Genetics Home Reference: your guide to understanding genetic conditions
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Craniofacial-deafness-hand syndrome

Reviewed August 2012

What is craniofacial-deafness-hand syndrome?

Craniofacial-deafness-hand syndrome is characterized by distinctive facial features, profound hearing loss, and hand abnormalities.

The distinctive facial features of people with craniofacial-deafness-hand syndrome result from a variety of developmental abnormalities involving the skull (cranium) and face. Affected individuals often have underdeveloped or absent nasal bones resulting in a small nose, thin nostrils, and a flattened mid-face with a flat nasal bridge. Individuals with this condition typically also have widely spaced eyes (ocular hypertelorism), narrowed openings of the eyes (narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips.

People with this condition also have profound hearing loss that is caused by abnormalities in the inner ear (sensorineural deafness). Hearing loss in these individuals is present from birth.

In affected individuals, a common abnormality of the muscles in the hand is a malformation in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). People with craniofacial-deafness-hand syndrome may also have permanently bent third, fourth, and fifth fingers (camptodactyly), which can limit finger movement and lead to joint deformities called contractures. Contractures in the wrist can further impair hand movements.

How common is craniofacial-deafness-hand syndrome?

Craniofacial-deafness-hand syndrome is an extremely rare condition. Only a few cases have been reported in the scientific literature.

What genes are related to craniofacial-deafness-hand syndrome?

Craniofacial-deafness-hand syndrome is caused by mutations in the PAX3 gene. The PAX3 gene plays a critical role in the formation of tissues and organs during embryonic development. To perform this function, the gene provides instructions for making a protein that attaches (binds) to specific areas of DNA to help control the activity of particular genes. During embryonic development, the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo. The protein produced from the PAX3 gene directs the activity of other genes that signal neural crest cells to form specialized tissues or cell types. These include some nerve tissues, bones in the face and skull (craniofacial bones), and muscle tissue.

At least one PAX3 gene mutation has been identified in individuals with craniofacial-deafness-hand syndrome. This mutation appears to affect the ability of the PAX3 protein to bind to DNA. As a result, the PAX3 protein cannot control the activity of other genes and cannot regulate the differentiation of neural crest cells. A lack of specialization of neural crest cells leads to the impaired growth of craniofacial bones, nerve tissue, and muscles seen in craniofacial-deafness-hand syndrome.

Related Gene(s)

Changes in this gene are associated with craniofacial-deafness-hand syndrome.

  • PAX3

How do people inherit craniofacial-deafness-hand syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of craniofacial-deafness-hand syndrome?

These resources address the diagnosis or management of craniofacial-deafness-hand syndrome and may include treatment providers.

  • Genetic Testing Registry: Craniofacial deafness hand syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1852510)
  • Johns Hopkins Children's Center: Hearing Loss (http://www.hopkinschildrens.org/hearing-loss.aspx)

You might also find information on the diagnosis or management of craniofacial-deafness-hand syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/craniofacial-deafness-hand-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about craniofacial-deafness-hand syndrome?

You may find the following resources about craniofacial-deafness-hand syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for craniofacial-deafness-hand syndrome?

  • CDHS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about craniofacial-deafness-hand syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding craniofacial-deafness-hand syndrome?

autosomal ; autosomal dominant ; camptodactyly ; cell ; craniofacial ; differentiation ; DNA ; embryo ; embryonic ; gene ; hypertelorism ; joint ; malformation ; mutation ; neural crest ; ocular hypertelorism ; protein ; sensorineural ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/8664898?dopt=Abstract)
  • Birrane G, Soni A, Ladias JA. Structural basis for DNA recognition by the human PAX3 homeodomain. Biochemistry. 2009 Feb 17;48(6):1148-55. doi: 10.1021/bi802052y. (http://www.ncbi.nlm.nih.gov/pubmed/19199574?dopt=Abstract)
  • Sommer A, Bartholomew DW. Craniofacial-deafness-hand syndrome revisited. Am J Med Genet A. 2003 Nov 15;123A(1):91-4. (http://www.ncbi.nlm.nih.gov/pubmed/14556253?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2012
Published: July 7, 2014