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 report 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 typical clinical and radiographic findings and/or a heterozygous pathogenic variant in , , , , or identified by molecular genetic testing.

MANAGEMENT

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. Evaluation by an orthopedic surgeon for chronic pain and/or limb deformities (genu varum, genu valgum). Obesity; exercise causing repetitive strain on affected joints.

GENETIC COUNSELING

By definition, autosomal dominant MED is inherited in an autosomal dominant manner. Many individuals with autosomal dominant MED have an affected parent. The proportion of individuals with autosomal dominant MED who have the disorder as the result of a pathogenic variant is unknown. Each child of an individual with autosomal dominant MED has a 50% chance of inheriting the pathogenic variant. Once the autosomal dominant MED-related pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.