Autosomal dominant otospondylomegaepiphyseal dysplasia

Autosomal dominant otospondylomegaepiphyseal dysplasia (OSMED), also known as Weissenbacher-Zweymüller syndrome or Stickler syndrome type III in some classifications, is a rare genetic skeletal disorder characterized by the combination of sensorineural hearing loss (oto-), vertebral abnormalities (spondylo-), and enlarged epiphyses of the long bones (megaepiphyseal dysplasia). This condition primarily affects the skeletal system, auditory system, and craniofacial structures. It is caused by heterozygous mutations in the COL11A2 gene, which encodes the alpha-2 chain of type XI collagen, a structural protein important for cartilage and bone development. Key clinical features include moderate to severe sensorineural hearing loss, midface hypoplasia (flattened facial profile), a depressed nasal bridge, and Pierre Robin sequence (micrognathia, cleft palate, and glossoptosis) that may be present at birth. Skeletal manifestations include platyspondyly (flattened vertebral bodies), enlarged and irregular epiphyses, short limbs, and short stature. Importantly, unlike other forms of Stickler syndrome, the autosomal dominant form of OSMED caused by COL11A2 mutations does not involve ocular abnormalities, since type XI collagen alpha-2 is not expressed in the vitreous humor of the eye. There is currently no cure for autosomal dominant OSMED, and management is supportive and multidisciplinary. Treatment typically includes hearing aids or cochlear implants for hearing loss, surgical correction of cleft palate if present, orthopedic monitoring and intervention for skeletal complications, and speech therapy. Regular audiological assessments and orthopedic follow-up are recommended throughout life. Early intervention for hearing loss is particularly important to support speech and language development in affected children.

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