Autosomal Dominant Deafness-Onychodystrophy Syndrome

A rare multiple congenital anomalies syndrome characterized by congenital hearing impairment, small or absent nails on the hands and feet, and small or absent terminal phalanges.

Epidemiology

The prevalence is unknown but it has been reported in 22 individuals from ten families to date.

Clinical description

The main clinical characteristics of dominant deafness-onychodystrophy (DDOD) syndrome are severe sensorineural hearing loss or deafness and onychodystrophy (small or absent fingernails and toenails, sometimes limited to the nails of the first and fifth digits). Brachydactyly, long, finger-like or tri-phalangeal thumbs as well as conical, hypoplastic teeth or oligodontia have also been reported in several patients. Syndactyly, minor facial dysmorphism (mild hypotelorism, deep set eyes and midface hypoplasia), and epilepsy have been seen in individual cases. Unlike DOORS syndrome, most patients with DDOD follow a normal development and have normal intelligence.

Etiology

DDOD syndrome is caused, in some cases, by heterozygous mutations in the ATP6V1B2 gene (8p21.3) encoding a vacuolar ATPase (V-ATPase) involved in protein translocation. It is at present unknown whether there can be genetic heterogeneity or not, as not all known families have been tested.

Diagnostic methods

Diagnosis is based on the presence of characteristic clinical findings. X-rays of the hands and feet and a brain stem auditory evoked response (BAER) test for hearing loss should be performed. Molecular genetic testing identifying a ATP6V1B2 mutation may confirm the diagnosis but as it is at present uncertain whether DDOD syndrome is genetically heterogeneous, the absence of a mutation will not mean that a diagnosis of DDOD syndrome is incorrect.

Differential diagnosis

The main differential diagnosis is DOORS syndrome and Coffin-Siris syndrome. The limb anomalies seen in DDOD syndrome can also be found in several other entities including Zimmermann-Laband syndrome, Adams-Oliver syndrome, Temple-Baraitser syndrome and Fontaine Progeroid Syndrome.

Antenatal diagnosis

Prenatal diagnosis of DDOD syndrome has not been performed to date.

Genetic counseling

DDOD syndrome is inherited autosomal dominantly so if the clinical diagnosis has been established reliably, genetic counseling is possible. In this case, affected families should be informed that risk of transmission from an affected parent to offspring is 50%.

Management and treatment

Treatment is supportive and involves special education for the hearing impaired as well as regular follow-up. Corrective surgery is in principle possible for those with syndactyly, although generally not necessary.

Prognosis

The disease is not life threatening. The main influence on quality of life is hearing loss.