Multiple Epiphyseal Dysplasia, Autosomal Dominant

Clinical characteristics: Autosomal dominant multiple epiphyseal dysplasia (MED) presents in early childhood, usually with pain in the hips and/or knees after exercise. Affected children complain of fatigue with long-distance walking. Waddling gait may be present. Adult height is either in the lower range of normal or mildly shortened. The limbs are relatively short in comparison to the trunk. Pain and joint deformity progress, resulting in early-onset osteoarthritis, particularly of the large weight-bearing joints.

Diagnosis/testing: The diagnosis of autosomal dominant MED is established in a proband with the typical clinical and radiographic findings and/or a heterozygous pathogenic variant in COL9A1, COL9A2, COL9A3, COMP, or MATN3 identified by molecular genetic testing.

Management: Treatment of manifestations: For pain control, a combination of analgesics and physiotherapy including hydrotherapy; referral to a rheumatologist or pain specialist as needed; consideration of realignment osteotomy and/or acetabular osteotomy to limit joint destruction and development of osteoarthritis. Consider total joint arthroplasty if the degenerative hip changes cause uncontrollable pain/dysfunction; offer psychosocial support addressing issues of short stature, chronic pain, disability, and employment.

Surveillance: Evaluation by an orthopedic surgeon for chronic pain and/or limb deformities (genu varum, genu valgum).

Agents/circumstances to avoid: Obesity; exercise causing repetitive strain on affected joints.

Genetic counseling: Many individuals with autosomal dominant MED have inherited the pathogenic variant from a parent. The prevalence of de novo pathogenic variants is not known. Each child of an individual with autosomal dominant MED has a 50% chance of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for autosomal dominant multiple epiphyseal dysplasia are possible if the pathogenic variant has been identified in an affected family member.