Teunissen–Cremers Syndrome

Overview

Teunissen–Cremers syndrome is a rare genetic disorder characterized by congenital conductive hearing loss and abnormalities of the middle ear bones, particularly the stapes. Also known as stapes ankylosis with broad thumbs and toes, this condition affects both auditory and skeletal development. Individuals with the syndrome typically present with bilateral hearing loss and mild but distinctive physical features, such as broad thumbs and halluces (big toes). First described by Dutch physicians Teunissen and Cremers in 1990, the syndrome is considered part of a group of otoskeletal disorders that involve anomalies in both hearing structures and limb morphology.

Causes

Teunissen–Cremers syndrome is caused by mutations in the NOG gene, which encodes the protein noggin. Noggin is essential for bone and joint development, particularly in regulating the formation of skeletal elements and joints during embryogenesis. Mutations in the NOG gene lead to abnormal bone growth and ossification, especially in areas like the middle ear and digits.

The condition follows an autosomal dominant inheritance pattern, meaning that a mutation in one copy of the NOG gene inherited from either parent is sufficient to cause the disorder. In some cases, the mutation may arise de novo, with no family history of the syndrome.

Symptoms

The clinical features of Teunissen–Cremers syndrome can vary but generally involve a combination of auditory and skeletal abnormalities. Key symptoms include:

Auditory Features:

• Congenital conductive hearing loss – Caused by stapes ankylosis, where the stapes bone is fixed and cannot transmit sound vibrations effectively.

• Progressive hearing loss – In some cases, hearing loss may worsen with age if not treated.

Skeletal Features:

• Broad thumbs and big toes (halluces) – Present at birth and usually bilateral.

• Short or hypoplastic distal phalanges – The end bones of fingers and toes may appear shorter than normal.

• Joint stiffness or limited mobility – Especially in the interphalangeal joints of the hands and feet.

• Possible radioulnar synostosis – A rare fusion of the radius and ulna bones in the forearm, limiting arm rotation.

Intelligence and general development are typically normal, and other organ systems are not usually affected.

Diagnosis

Diagnosis of Teunissen–Cremers syndrome is based on clinical findings, audiological evaluation, imaging studies, and genetic testing. Key diagnostic steps include:

• Physical examination – Identification of broad thumbs and toes, along with any limb abnormalities.

• Hearing assessment – Audiometry confirms conductive hearing loss, and tympanometry may show immobile stapes.

• CT scan of the temporal bones – Reveals stapes ankylosis or other middle ear malformations.

• Family history review – Identification of similar findings in other family members may support a hereditary pattern.

• Genetic testing – Detection of a pathogenic variant in the NOG gene confirms the diagnosis.

Differential diagnosis includes other genetic disorders involving conductive hearing loss and skeletal abnormalities, such as otosclerosis, proximal symphalangism, and multiple synostoses syndrome.

Treatment

Treatment for Teunissen–Cremers syndrome focuses primarily on managing the hearing loss and monitoring skeletal issues. There is no cure for the genetic mutation, but early intervention can significantly improve quality of life. Treatment strategies include:

1. Hearing Management:

• Hearing aids – Useful for individuals with moderate to severe conductive hearing loss.

• Surgical intervention – Stapedectomy or stapedotomy can be performed to replace or mobilize the stapes bone, potentially restoring hearing.

• Cochlear implants – Rarely needed unless the hearing loss has a sensorineural component or surgical correction is unsuccessful.

2. Orthopedic Management:

• Physical therapy – Helps maintain joint flexibility and function in cases with joint stiffness.

• Orthopedic evaluation – For individuals with more significant skeletal deformities or functional limitations.

3. Genetic Counseling:

• Recommended for affected individuals and their families to understand inheritance patterns, recurrence risk, and family planning options.

Prognosis

The overall prognosis for individuals with Teunissen–Cremers syndrome is excellent, especially with early recognition and intervention for hearing loss. Key points include:

• Normal lifespan – The syndrome does not affect life expectancy.

• Normal cognitive development – Intelligence is unaffected.

• Good outcomes with treatment – Surgical and audiologic interventions can significantly improve hearing and quality of life.

• Variable skeletal symptoms – While joint and digit abnormalities may affect fine motor function, most individuals adapt well with little to no disability.

With appropriate care and monitoring, individuals with Teunissen–Cremers syndrome can lead healthy, productive lives.