Background: Most patients with progressive pseudorheumatoid dysplasia (PPRD) are initially misdiagnosed because of disease rarity and lack of awareness by most clinicians. The purpose of this present study was to provide further early diagnostic options and potential treatment to patients with PPRD.
Methods: This was a retrospective study. Clinical manifestations, laboratory test results, radiographic features, Sanger Sequencing to determine CCN6 gene variants, treatment and follow-up records were collected in the patients with PPRD. Time to diagnosis, phenotype and genotype correlation were analyzed.
Results: Nine PPRD children were included. There were 3 pairs of siblings and one patient had parental consanguinity. Five patients were misdiagnosed as juvenile idiopathic arthritis (JIA). The onset of disease in 8 patients was between 3 to 6 years of age. The interval from onset of symptoms to obtaining the diagnosis for 8 of the patients varied from 3.6 years to 20 years. The onset of symptoms included enlarged and stiff interphalangeal joints of the fingers, gait disturbance or joint pain. Laboratory tests revealed normal range of inflammatory parameters. Serum levels of 25-hydroxyvitamin D3 in six patients were below the normal range. Radiographic findings included different degree of abnormal vertebral bodies, epiphyseal enlargement of the interphalangeal joints with juxta-articular osteopenia, or cyst-like structures femoral head. All the patients harbored CCN6 variants, and a total of 7 variants were identified. After the treatment of calcitriol in 5 patients with low level of 25-hydroxyvitamin D3 for 1.25 years to 1.75 years, two of them kept stable, while 3 of them improved gradually.
Conclusions: Combining the patient’s family history, clinical features presenting with abnormal gait or enlarged and stiff interphalangeal joints of the fingers, normal inflammatory markers, and the characteristic radiographic findings, we can obtain the clinical diagnosis of PPRD for the patients at a very early stage of the disease. Anterior blunt of the vertebral bodies could be an early radiological sign in the patient even without obvious clinical symptoms and characteristics yet. The patients with PPRD having c.624dupA variant in CCN6 may have delayed onset. Underlying vitamin D deficiency should be sought and corrected in patients with PPRD. Keywords: progressive pseudorheumatoid dysplasia; noninflammatory; articular cartilage; CCN6 gene variant; vitamin D deficiency