Multiple epiphyseal dysplasia is considered a rare disorder, with the autosomal dominant form diagnosed in about 1 in 10,000 live births. The prevalence of the recessive form is unknown and is believed to be more rare than the dominant form, though underdiagnosis makes this difficult to ascertain. Both males and females are affected equally. Because symptoms can range from mild to severe, many mild cases may remain undiagnosed or misdiagnosed as juvenile arthritis or idiopathic short stature.

MED is caused by genetic mutations that disrupt the formation of cartilage and bone at the growth plates. The autosomal dominant form most commonly results from mutations in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 genes, all of which are involved in the development of proteins that support the structure and stability of cartilage. Out of these genetic mutations, the majority of individuals with MED have mutations in the COMP gene, which prevents the release of proteins that would normally lead to the development of cartilage. 

The recessive form is usually caused by mutations in the SLC26A2 gene, which affects cartilage matrix formation and sulfate transport. These genetic defects impair the development of the cartilage template necessary for proper ossification (cartilage conversion to bone), leading to small, irregular, or flattened epiphyses (ends of long bones that connect to joint surfaces).

The symptoms of MED typically appear in early to middle childhood and may include:

• Joint pain and stiffness, especially in the hips and knees, which often worsen after physical activity

• Short stature or mild shortness of limbs, although height is usually near the lower end of normal

• Gait abnormalities, such as a waddling or limping walk due to hip deformities

• Early-onset osteoarthritis, often developing in adolescence or early adulthood

• Limited range of motion in affected joints

• Mild deformities such as coxa vara (deformity of the hip joint) or genu valgum (knock knees)

• Disruption of blood flow to the joints (avascular necrosis)

• Normal facial features, intelligence, and spine, distinguishing MED from other skeletal dysplasias like spondyloepiphyseal dysplasia

Recessive multiple epiphyseal dysplasia is distinguished from dominant by abnormal curvature of the hands, feet, knees, and spine (scoliosis). About 50% of those born with the autosomal recessive form of MED also have one of the following physical abnormalities:

• Inward/upward turning foot (clubfoot)

• Opening in the roof of the mouth/upper lip (cleft palate)

• Curved fingers/toes (clinodactyly)

• Ear swelling

• Abnormal kneecap called a double-layered patella

Diagnosis of MED is based on clinical evaluation, radiographic findings, and genetic testing. Children often present with joint discomfort and mild skeletal disproportion, prompting imaging studies. X-rays typically reveal irregular, fragmented, or small epiphyses in multiple joints, while the spine appears normal. Family history and genetic testing help confirm the diagnosis and identify the inheritance pattern.

• X-rays (radiographs): Show delayed ossification, flattened or irregular epiphyses, and signs of early arthritis. The metaphyses (shaft regions) are typically normal.

• MRI or CT scans: May be used to assess cartilage structure, joint integrity, and early osteoarthritis.

• Genetic testing: Confirms pathogenic variants in COMP, MATN3, COL9A1-3, or SLC26A2 genes, which also helps differentiate between dominant and recessive forms.

• Family history assessment: Identifies inheritance patterns and helps with genetic counseling.

There is no cure for MED, and treatment focuses on symptom management and preserving joint function. A multidisciplinary approach involving orthopedists, physical therapists, and genetic specialists is typically required.

• Physical therapy: Helps maintain joint flexibility and muscle strength, reducing pain and improving mobility.

• Pain management: Includes nonsteroidal anti-inflammatory drugs (NSAIDs) for joint pain and inflammation.

• Guided growth of the lower extremities (hemiepiphysiodesis) to help correct deformities

• Realignment surgery of the hips

• Orthopedic interventions: Corrective surgery may be needed for severe deformities or misalignment, such as osteotomy for hip or knee correction.

• Joint replacement surgery: In adulthood, joint replacement (especially of the hips or knees) may be necessary for severe arthritis.

• Lifestyle modifications: Low-impact physical activities (e.g., swimming, cycling) are recommended to minimize joint stress.

The prognosis for individuals with MED is generally good, with normal life expectancy. However, chronic joint pain and early-onset osteoarthritis can significantly impact quality of life. Most affected individuals can lead active, independent lives, although they may require orthopedic procedures or joint replacements in later adulthood. The dominant form tends to be milder, while the recessive form may present with more severe skeletal abnormalities and earlier symptom onset. Regular monitoring, early physical therapy, and surgical management of joint problems can help preserve long-term mobility and function.

1. Multiple epiphyseal dysplasia: Medline Plus

2. Multiple epiphyseal dysplasia: Johns Hopkins Medicine

3. Multiple epiphyseal dysplasia: Pediatrics - Orthobullets