ESPE Abstracts

Introduction: Progressive pseudorheumatoid dysplasia (PPRD) is a rare genetic bone disorder characterised by the progressive degeneration of articular cartilage leading to pain, stiffness, joint enlargement and short stature. PPRD occurs due to a mutation in cellular communication network factor 6 (CCN6)/Wnt1-inducible signalling protein 3 (WISP3) gene, encoding a 354 amino acid signalling factor involved in BMP/WNT signalling and mitochondrial function. Diagnosis is based on clinical and radiographic findings and confirmed by genetic analysis.

Case: A female, born with normal birth weight to consanguineous parents, presented at 4 years with a waddling gait, mild cavovarus foot deformity with restricted joint movements. She had poor growth from age 5. At age 11.7 years, when referred to Paediatric Endocrinology, her height was -2.33 SDS, BMI +3.0 SDS, head circumference +1.1 SDS. She had restricted extension of fingers, elbows, knees and ankles. She attained menarche at 13 years; (near) final height was 136 cm (-4.0 SDS). She had autoantibody-negative insulin-dependent diabetes mellitus with low C-peptide. Her developmental milestones, hearing and vision were normal. Mother was 157.8 cm, father’s height was unknown. Maternal grandmother suffered from arthritis. Two cousins had insulin-dependent diabetes.

Results: She was initially investigated by neuromuscular and rheumatological teams. MRI brain and spine were initially normal; EMG suggested muscle pathology with normal creatinine kinase and muscle biopsy. Inflammatory markers were normal with radiological abnormalities. Bone age was 13 years at chronological age 11.1 years. IGF-1 was 138 mg/l (101-576.3) and IGFBP3 2.7 mg/l (2.4-6.1). Skeletal survey at 12 years was suggestive of PPRD and showed loss of joint space and widened metaphyses but no erosion in several joints. Vertebrae showed platyspondyly with anterior ossification defects, and supracetabular lipping of the iliac bones. Skeletal dysplasia gene panel analysis showed a previously reported pathogenic homozygous c.210C>A (P.Cys70*) nonsense variant in CCN6/WISP3. Further family testing was recommended but declined.

Discussion: PPRD presents usually between ages of 3 to 6 years with slowing growth and progressive involvement of the metacarpophalangeal (MCP), proximal (PIP) and distal interphalangeal (DIP) joints, wrists, elbows, knees, shoulders, and ankle joints. PPRD can be initially misdiagnosed as juvenile rheumatoid arthritis but is distinguished on radiographic analysis and the absence of inflammatory joint disease. This diagnosis is important to avoid unnecessary immunosuppressant therapy. This case emphasises the usefulness of radiographic skeletal survey as an investigative tool in short stature, even without disproportion.