Yin Lei, Mao Youying, Zhou Yunfang, Shen Yongnian, Chen Huijin, Zhou Wei, Jin Yanliang, Huang Hua, Yu Yongguo, Wang Jian
Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, People's Republic of China.
Special Consultation Clinic for Rare and Complicated Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Clin Rheumatol. 2022 Mar;41(3):877-888. doi: 10.1007/s10067-021-05959-2. Epub 2021 Oct 21.
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 study was to provide further early diagnostic options and potential treatment to patients with PPRD.
A retrospective study was performed by collecting and organizing clinical manifestations, radiographic features, laboratory test results, genetic test outcome, treatment, and follow-up records of the patients with PPRD. Age of diagnosis and genotype-phenotype correlation were further analyzed.
Nine PPRD children with causative CCN6 mutation were included. There were 3 pairs of siblings and 1 patient from inbred family. Five patients were primarily misdiagnosed as juvenile idiopathic arthritis (JIA). The interval between onset of symptoms and definite diagnosis of 8 patients varied from 3.6 to 20 years. Symptoms at the onset included enlarged and stiff interphalangeal joints of the fingers, gait disturbance, or joint pain. Laboratory tests revealed normal range of inflammatory parameters. Radiographic findings disclosed different degrees of abnormal vertebral bodies and epiphyseal enlargement of the interphalangeal joints. After the treatment of calcitriol in 5 patients with low level 25-hydroxyvitamin D3 for around 1.25 years to 1.75 years, 2 patients kept stable, while 3 of them improved gradually.
Combining the patient's family history, clinical features, normal inflammatory markers, and the characteristic radiographic findings, the clinical diagnosis of PPRD for the patients could be obtained at very early stage of the disease. The patients with PPRD carrying c.624dupA variant in CCN6 may have delayed onset. Underlying vitamin D deficiency should be sought and corrected in patients with PPRD.
大多数进行性假类风湿性发育不良（PPRD）患者最初会被误诊，原因是该疾病罕见且大多数临床医生对此缺乏认识。本研究的目的是为PPRD患者提供更多早期诊断选择和潜在治疗方法。
通过收集和整理PPRD患者的临床表现、影像学特征、实验室检查结果、基因检测结果、治疗及随访记录进行回顾性研究。进一步分析诊断年龄和基因型-表型相关性。
纳入9例携带CCN6致病突变的PPRD儿童。有3对兄弟姐妹和1例来自近亲家庭的患者。5例患者最初被误诊为幼年特发性关节炎（JIA）。8例患者从症状出现到明确诊断的间隔时间为3.6至20年。发病时的症状包括手指指间关节肿大、僵硬、步态障碍或关节疼痛。实验室检查显示炎症参数在正常范围内。影像学检查发现椎体有不同程度的异常以及指间关节骨骺增大。5例25-羟基维生素D3水平低的患者接受骨化三醇治疗约1.25至1.75年后，2例病情稳定，3例逐渐好转。
结合患者家族史、临床特征、正常炎症标志物和特征性影像学表现，可在疾病的极早期对PPRD患者做出临床诊断。携带CCN6基因c.624dupA变异的PPRD患者可能发病较晚。对于PPRD患者，应寻找并纠正潜在的维生素D缺乏。
