Craniometaphyseal dysplasia

Craniometaphyseal dysplasia (CMD) is a rare genetic skeletal disorder characterized by progressive thickening (hyperostosis) and sclerosis of the bones of the skull and face (cranium), combined with abnormal widening (flaring) of the metaphyses of long bones. The condition primarily affects the skeletal system, with the craniofacial changes being the most clinically significant. Progressive overgrowth of craniofacial bones leads to a characteristic facial appearance with a wide nasal bridge, paranasal bossing, and a broad, prominent jaw. The bony overgrowth can narrow cranial foramina, potentially compressing cranial nerves and leading to complications such as facial nerve palsy (Bell's palsy), hearing loss (both conductive and sensorineural), visual impairment, and, in severe cases, increased intracranial pressure. Nasal obstruction due to bony overgrowth of the paranasal region is a common and early symptom, often causing mouth breathing and recurrent upper respiratory infections. Craniometaphyseal dysplasia exists in two forms: an autosomal dominant form (more common, generally milder) caused by mutations in the ANKH gene, and an autosomal recessive form (rarer, typically more severe) for which the genetic basis has been linked to mutations in the GJA1 gene in some cases. The metaphyseal flaring of long bones, particularly evident at the knees, is often noted in childhood and may improve with age, while the cranial hyperostosis tends to be progressive throughout life. There is no cure for craniometaphyseal dysplasia. Treatment is primarily supportive and symptomatic. Surgical intervention may be necessary to decompress cranial nerves, relieve nasal obstruction, or reduce intracranial pressure, though bony regrowth after surgery is common. Calcitriol and calcitonin have been tried in some cases to reduce bone overgrowth, but results have been inconsistent. Regular monitoring by a multidisciplinary team including otolaryngologists, ophthalmologists, neurologists, and orthopedic specialists is recommended to manage complications as they arise.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Craniometaphyseal dysplasia