Chondrodysplasia with Congenital Joint Dislocations, CHST3-Related

Clinical characteristics: Chondrodysplasia with congenital joint dislocations, CHST3-related (CDCJD-CHST3) 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 of CDCJD-CHST3 is established in a proband with characteristic clinical and radiographic features and biallelic pathogenic variants in CHST3 identified by molecular genetic testing.

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. Treatment of cardiac manifestations as needed per cardiologist; treatment of dental anomalies as needed per dentist.

Surveillance: Clinical joint and spine evaluation with orthopedist with experience in skeletal dysplasia; radiographs as recommended per orthopedist; if normal at the time of diagnosis, echocardiogram should be repeated per cardiologist or every five years; follow up with dentist annually or as needed.

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

Genetic counseling: CDCJD-CHST3 is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CHST3 pathogenic variant, each sib of an affected individual has a 25% chance at conception of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the CHST3 pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members and prenatal/preimplantation genetic testing for a pregnancy at increased risk are possible.