SOST-Related Sclerosing Bone Dysplasias

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation.

The major clinical features of sclerosteosis are progressive skeletal overgrowth, most pronounced in the skull and mandible, and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly. Facial distortion due to bossing of the forehead and mandibular overgrowth is seen in nearly all individuals and becomes apparent in early childhood with progression into adulthood. Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the seventh cranial nerve (leading to facial palsy) with other, less common nerve entrapment syndromes including visual loss (2nd cranial nerve), neuralgia or anosmia (5th cranial nerve), and sensory hearing loss (8th cranial nerve). In sclerosteosis, hyperostosis of the calvarium reduces intracranial volume, increasing the risk for potentially lethal elevation of intracranial pressure. Survival of individuals with sclerosteosis into old age is unusual, but not unprecedented.

The manifestations of van Buchem disease are generally milder than sclerosteosis and syndactyly is absent; life span appears to be normal.

Diagnosis/testing: The diagnosis of SOST-related sclerosing bone dysplasia is established in a proband with typical clinical and radiographic findings and identification of biallelic pathogenic variants in SOST (for sclerosteosis) or the presence of a biallelic 52-kb deletion downstream of SOST (for van Buchem disease) on molecular genetic testing.

Management: No specific treatment is currently available, and management aims at relieving symptoms and preventing complications.

Treatment of manifestations: Surgical correction of syndactyly; surgical decompression of entrapped cranial nerves, notably the facial nerve; craniectomy and ventriculo-peritoneal drain for increased intracranial pressure; surgical reduction of mandibular overgrowth; hearing aids with middle ear surgery or cochlear implant depending on nature of hearing loss; spinal cord decompression for radiculopathy; orbital decompression for proptosis or glaucoma.

Surveillance: At least annual assessments from infancy for bone mass, evidence of cranial nerve entrapment and of increased intracranial pressure, vision issues, hearing loss, and tooth malalignment/malocclusion.

Agents to avoid: Agents known to suppress bone resorption (e.g., bisphosphonates, denosumab, selective estrogen receptor modulators) and agents known to stimulate bone formation (e.g., teriparatide, abaloparatide, romozosumab).

Genetic counseling: SOST-related sclerosing bone dysplasia is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis for pregnancies at increased risk and preimplantation diagnosis for SOST-related sclerosing bone dysplasias are possible if the pathogenic variants in the family have been identified. Ultrasound examination may detect syndactyly in fetuses at risk for sclerosteosis, but its absence on ultrasound examination does not rule out an affected fetus.

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