Schmid Metaphyseal Chondrodysplasia

Clinical characteristics: Schmid metaphyseal chondrodysplasia (SMCD) is characterized by progressive short stature that develops by age two years. The clinical and radiographic features are usually not present at birth, but manifest in early childhood with short limbs, genu varum, and waddling gait. Facial features and head size are normal. Radiographs show metaphyseal irregularities of the long bones (e.g., splaying, flaring, cupping); shortening of the tubular bones; widened growth plates; coxa vara; and anterior cupping, sclerosis, and splaying of the ribs. Mild hand involvement often includes shortening of the tubular bones and metaphyseal cupping of the metacarpals and proximal phalanges. Platyspondyly and vertebral end-plate irregularities are less common. Hand and vertebral involvement can resolve with age. Early motor milestones may be delayed due to orthopedic complications. Intelligence is normal. Joint pain in the knees and hips is common and may limit physical activity. Adult height is typically more than 3.5 SD below the mean, although a wide spectrum that overlaps normal height has been reported. There are no extraskeletal manifestations.

Diagnosis/testing: The diagnosis of SMCD is established in a proband with characteristic clinical and radiographic features and/or identification of a heterozygous pathogenic variant in COL10A1 by molecular genetic testing.

Management: Treatment of manifestations: Management of orthopedic complications by orthopedist, physiotherapist, occupational therapist, and pain specialist as indicated. Joint-friendly exercise, weight management; mobility device as needed; corrective osteotomy by guided growth surgery or valgus osteotomy may be considered in late childhood / adolescence in those with progressive or symptomatic varus deformity, significant coxa vara, triangular fragment in the interior femoral neck, or poor or deteriorating function; exercise and support from nutritionist to maintain healthy weight; psychosocial support; environmental or occupational modifications as needed for short stature with recommendations from occupational therapy as needed.

Surveillance: Annual growth assessment, clinical evaluation for orthopedic manifestations, and psychosocial evaluation.

Agents/circumstances to avoid: Obesity; physical activities that cause excessive joint strain.

Genetic counseling: SMCD is inherited in an autosomal dominant manner. Most individuals diagnosed with SMCD have the disorder as the result of a de novo COL10A1 pathogenic variant. Some individuals diagnosed with SMCD have an affected parent. Each child of an individual with SMCD has a 50% chance of inheriting the COL10A1 pathogenic variant. If the proband and the proband's reproductive partner are affected with different dominantly inherited skeletal dysplasias, genetic counseling becomes more complicated because of the risk of inheriting two dominantly inherited bone growth disorders. If the COL10A1 pathogenic variant has been identified in the affected parent, prenatal testing for a pregnancy at increased risk for SMCD and preimplantation genetic testing are possible.