autosomal dominant deafness - onychodystrophy syndrome

Autosomal dominant deafness-onychodystrophy (DDOD) syndrome is a very rare genetic condition that primarily affects hearing, nail development, and the small bones at the tips of the fingers and toes. It is present from birth and results from changes in the ATP6V1B2 gene, which provides instructions for part of a cellular protein complex involved in acid-base balance within cells. Both males and females can be affected, and because the condition follows an autosomal dominant inheritance pattern, one altered gene copy is sufficient to cause symptoms. Fewer than one in a million people are estimated to have DDOD syndrome worldwide. Although the core features are consistent, the overall severity and additional findings vary widely between individuals.

The most characteristic findings are bilateral sensorineural hearing impairment that is usually severe from birth and abnormalities of the nails, which may be small, thin, or completely absent on both fingers and toes. Many affected people also have distinctive hand differences, including thumbs with three bones (triphalangeal thumbs) and shortened or missing middle phalanges, especially of the fifth fingers. Less common but important features can involve other body systems. About one third of individuals have dental differences such as missing (oligodontia) or small conical teeth, and flat feet (pes planus) or areas of absent skin at birth (aplasia cutis) have been reported in some cases. Cognitive or developmental concerns—including mild intellectual disability, speech delay, or seizures—occur in a minority of individuals, reminding families that the condition can extend beyond the ears and nails. Not all individuals experience all features, and severity varies considerably. Regular evaluations by specialists familiar with hearing, skeletal, dermatologic, and developmental issues can help identify and address emerging concerns early.

DDOD syndrome is caused by pathogenic variants in the ATP6V1B2 gene. The gene encodes a subunit of the vacuolar H⁺-ATPase, a protein complex that helps regulate acidity inside many types of cells. When one copy of ATP6V1B2 does not function properly, tissues that rely on precise pH control during development—such as the inner ear, nail beds, and the ends of small bones—are particularly vulnerable. The condition is inherited in an autosomal dominant pattern, meaning a person who has the pathogenic variant has a 50 percent chance of passing it to each child. Most families described so far have multiple affected members across generations, although new (de novo) variants are possible. Because symptoms can vary even within the same family (variable expressivity), genetic counseling is recommended for relatives who may be at risk and for family planning discussions.

Currently, management focuses on supportive care and symptom management tailored to each individual’s needs. Early fitting of hearing aids or consideration of cochlear implantation can significantly improve auditory input and support speech development. Regular assessments by audiology, speech-language therapy, and educational specialists help children reach their communication potential. Nail abnormalities are usually cosmetic but can lead to discomfort or infections; protective care of fingertips and toenail beds, as well as consultation with dermatology or hand surgery, may be helpful. Orthopedic evaluation can guide management of triphalangeal thumbs or foot alignment issues, and dental follow-up is important for tooth agenesis or abnormal tooth shape. Because DDOD syndrome affects multiple organ systems, long-term care is best provided by a multidisciplinary team that may include otolaryngology, audiology, orthopedics, dermatology, dentistry, and developmental specialists. Regular surveillance for hearing stability, skeletal growth, and developmental progress helps detect complications early, and genetic counseling offers guidance for affected individuals and their relatives.

Most individuals with DDOD syndrome have stable but lifelong hearing loss and nail differences. Overall health and life expectancy are generally good, especially when hearing impairment is addressed promptly and any developmental or orthopedic issues receive appropriate support. Severity and symptoms vary widely between individuals, even within the same family, and additional cognitive or seizure concerns are uncommon but possible. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists experienced in congenital hearing loss and skeletal differences, and genetic counseling can provide valuable information for future family planning.