Delayed-onset progressive pseudorheumatoid dysplasia with secondary synovial chondromatosis

Abstract

A 25-year-old man presented to us with progressive multiple joint pain, enlargement, and restricted movements. X-rays showed platyspondyly, multiple epiphyseal widening, synovial chondromatosis, and decreased bone stock and cortical thickness. Genetic testing showed biallelic pathogenic variants in CCN6 which confirmed the diagnosis of progressive pseudorheumatoid dysplasia. Supportive care, physical therapy, genetic and psychological counselling were provided to the patient.

Ccn6 Is Required for Mitochondrial Integrity and Skeletal Muscle Function in Zebrafish

“…Taken together, our study on zebrafish reveals a crucial role of Ccn6 in mitochondrial respiration and the maintenance of muscle integrity. In light of the fact that CCN6 mutations cause muscle weakness in PPRD ( Hurvitz et al, 1999 ; Dalal et al, 2012 ; Garcia Segarra et al, 2012 ; Sun et al, 2012 ; Ekbote et al, 2013 ; Yang et al, 2013 ; Liu et al, 2015 ; Luo et al, 2015 ; Alawbathani et al, 2018 ; Shahi et al, 2020 ), our findings open up a new theme in the study of CCN6 in the context of PPRD pathogenesis. The results garnered from this new direction of research may lead to significant progress in the diagnosis and understanding of PPRD and similar musculoskeletal disorders.…”

“…Since most tissues and cell types need a functional mitochondria for survival, one may wonder why PPRD-related defects due to CCN6 mutations are manifested only in skeletal tissues ( Hurvitz et al, 1999 ; Dalal et al, 2012 ; Garcia Segarra et al, 2012 ; Sun et al, 2012 ; Ekbote et al, 2013 ; Yang et al, 2013 ; Liu et al, 2015 ; Luo et al, 2015 ; Shahi et al, 2020 ). Perhaps the mitochondrial distribution pattern of Ccn6 varies among the different cell and tissue types, and accordingly, the influence of ccn6 mutations is more marked in skeletal tissues as compared to others.…”

“…Progressive pseudorheumatoid dysplasia, an incurable debilitating disorder, is characterized by loss of cartilage, muscle weakness, and irregular bone growth especially in the joints ( Hurvitz et al, 1999 ; Dalal et al, 2012 ; Sun et al, 2012 ; Ekbote et al, 2013 ; Yang et al, 2013 ; Liu et al, 2015 ; Luo et al, 2015 ; Chouery et al, 2017 ; Alawbathani et al, 2018 ; Shahi et al, 2020 ). But how CCN6 gene mutations lead to defects in cartilage and muscle remains unclear at the molecular level.…”

CCN6 influences transcription and controls mitochondrial mass and muscle organization

“…Association of CCN6 mutations with skeletal abnormalities indicates that CCN6 is especially important for skeletal growth and differentiation. Mutations spanning the different exons of CCN6 have been linked to a debilitating musculoskeletal disease termed Progressive Pseudo Rheumatoid Dysplasia (PPRD), [9][10][11][12][13][14][15][16][17] implying that lack of proper CCN6 function is associated with the development of PPRD.…”