Craniofacial deafness hand syndrome

Other Names: CDHS; Features of flat facial profile, hypertelorism, hypoplastic nose with slitlike nares, and a sensorineural hearing loss; Sommer-Young-Wee-Frye syndrome

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

Epidemiology

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

Cause 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.

Learn more about the gene associated with Craniofacial-deafness-hand syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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.

Signs and symptoms

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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Aplasia/Hypoplasia involving the nose(Decreased nasal size)
• Blepharophimosis(Narrow opening between the eyelids)
• Depressed nasal bridge(Depressed bridge of nose)
• Depressed nasal ridge(Flat nose)
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Flat face(Flat facial shape)
• Hypertelorism(Wide-set eyes)
• Hypoplasia of the maxilla(Decreased size of maxilla)
• Lacrimal duct atresia(Unopened tear duct)
• Narrow face(Decreased breadth of face)
• Narrow mouth(Small mouth)
• Sensorineural hearing impairment
• Short nose(Decreased length of nose)
• Ulnar deviation of finger(Finger bends toward pinky)
• Ulnar deviation of the wrist

30%-79% of people have these symptoms

• Camptodactyly of finger(Permanent flexion of the finger)

Diagnosis

Clinical tests

• Molecular Genetics Tests
• Targeted variant analysis
• Deletion/duplication analysis
• Sequence analysis of select exons
• Sequence analysis of the entire coding region

NIH genetic and rare disease info

• NIH info on Craniofacial deafness hand syndrome

Craniofacial deafness hand syndrome is a rare disease.