SNP Shot: Genomic Insights

SOST-related sclerosing bone dysplasia is a bone development disorder characterized by excessive bone formation, known as hyperostosis. This hyperostosis leads to abnormally dense and wide bones throughout the body, especially in the skull. Individuals with this condition commonly exhibit an enlarged jaw with misaligned teeth, a sunken midface (midface hypoplasia), bulging eyes with shallow eye sockets (ocular proptosis), and a prominent forehead. Headaches are frequent due to increased skull bone thickness putting pressure on the brain. The excessive bone formation is progressive, meaning skeletal features become more noticeable over time, although it may be localized to specific areas.

This abnormal bone growth can compress cranial nerves, which originate in the brain and extend to the head and neck. This compression can result in facial paralysis (facial nerve palsy), hearing loss, vision loss, and a reduced (hyposmia) or absent (anosmia) sense of smell. Critically, compression of the brainstem due to abnormal bone growth can lead to life-threatening complications.

SOST-related sclerosing bone dysplasia exists in two forms: sclerosteosis and van Buchem disease, distinguished by the severity of their symptoms.

Sclerosteosis represents the more severe form. Individuals with sclerosteosis are often tall and exhibit webbed or fused fingers (syndactyly), most commonly between the second and third fingers. Syndactyly is present at birth, while skeletal features typically emerge in early childhood. Absent or malformed nails may also be present.

Van Buchem disease is the milder form of the disorder. Individuals with van Buchem disease are typically of average height and do not have syndactyly or nail abnormalities. Cranial nerve compression tends to be less severe, resulting in milder neurological symptoms. Skeletal features in individuals with van Buchem disease typically appear during childhood or adolescence.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. The parents, who each carry only one copy of the mutated gene, are typically asymptomatic.