SLC26A2-Related Multiple Epiphyseal Dysplasia

Clinical characteristics: SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, including clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.

Diagnosis/testing: Diagnosis of SLC26A2-MED is based on detection of biallelic variants in SLC26A2 by molecular genetic testing in an individual with compatible clinical and radiographic findings.

Management: Treatment of manifestations: Physiotherapy for muscular strengthening and maintaining mobility; cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs; orthopedic surgery (joint replacement) as indicated; career counseling.

Prevention of secondary complications: Intensive physiotherapy may help in delaying joint contractures and maintaining mobility.

Surveillance: Radiographs as indicated.

Agents/circumstances to avoid: Sports involving joint overload.

Genetic counseling: SLC26A2-MED is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SLC26A2 pathogenic variant, each sib of an affected individual has at conception 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. Once the SLC26A2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.