Progressive Pseudorheumatoid Dysplasia

Clinical characteristics: Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Onset – typically between ages three and six years – begins with the involvement of the interphalangeal joints. Over time, involvement of large joints and the spine causes significant joint contractures, gait disturbance, and scoliosis and/or kyphosis, resulting in abnormal posture and significant morbidity. Despite the considerable arthropathy, pain is not a major presenting feature of this condition. Initially height is normal; however, short stature (<3rd centile) becomes evident in adolescence as the skeletal changes progress.

Diagnosis/testing: The diagnosis of PPD is established in a proband with characteristic radiographic features and/or identification of biallelic pathogenic variants in CCN6 (formerly WISP3) on molecular genetic testing.

Management: Treatment of manifestations: Treatment is supportive. Pain due to secondary osteoarthritis may respond to nonsteroidal anti-inflammatory drugs. Severe joint pain due to advanced osteoarthritis is treated by joint arthroplasty. Large joint stiffness is managed by physical therapy, activity modification, and walking aids. Small joint arthropathy is managed by an occupational therapist who may advise adaptive devices, modification of activity, and/or vocational training. Scoliosis and mild kyphosis may be treated with bracing. Surgical treatment for angular deformities of the lower limbs as per orthopedic surgeon.

Surveillance: Monitoring for orthopedic complications including bone deformity, secondary joint disease, spinal deformities, and pain. Annual evaluation by specialist(s) in skeletal dysplasia.

Agents/circumstances to avoid: Immobilization (e.g., casting).

Pregnancy management: Deformities of the pelvis may necessitate delivery by cæsarean section.

Genetic counseling: PPD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CCN6 pathogenic variant, each sib of an affected individual has at conception 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 relatives and prenatal testing for pregnancies at increased risk are possible if both CCN6 pathogenic variants have been identified in an affected family member.