CHST3-Related Skeletal Dysplasia

Clinical characteristics: CHST3-related skeletal dysplasia is characterized by short stature of prenatal onset, joint dislocations (knees, hips, radial heads), clubfeet, and limitation of range of motion that can involve all large joints. Kyphosis and occasionally scoliosis with slight shortening of the trunk develop in childhood. Minor heart valve dysplasia has been described in several persons. Intellect and vision are normal.

Diagnosis/testing: The diagnosis is based on the radiographic features of progressive spondyloepiphyseal dysplasia with joint anomalies, spinal abnormalities, normal thumbs (not spatulate), and normal bone age. CHST3 is the only gene in which pathogenic variants are known to cause CHST3-related skeletal dysplasia.

Management: Treatment of manifestations: Surgical correction of the abnormal joints is the only treatment modality; however, surgical correction is often only partially successful and multiple procedures are needed. Physical therapy has not been effective.

Surveillance: If normal at the time of diagnosis, echocardiogram should probably be repeated every five years.

Agents/circumstances to avoid: Activities with a high impact on joints (e.g., jogging) and obesity.

Genetic counseling: CHST3-related skeletal dysplasia is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has 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. Carrier testing for at-risk family members and prenatal testing for a prengancy at increased risk are possible if the pathogenic variants in the family have been identified.