Radiographic Features of Progressive Pseudorheumatoid Arthritis

Kozlowski, K.; Kennedy, J R; Lewis, Ian C.

doi:10.1111/j.1440-1673.1986.tb01748.x

Cited by 20 publications

(8 citation statements)

References 5 publications

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“…1). The hands are affected first, then the knees, hips, spine and other large joints as the disease progresses [2][3][4][5][6][7] . Loss of articular cartilage continues after skeletal growth is completed.…”

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confidence: 99%

Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia

et al. 1999

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Members of the CCN (for CTGF, cyr61/cef10, nov) gene family encode cysteine-rich secreted proteins with roles in cell growth and differentiation. Cell-specific and tissue-specific differences in the expression and function of different CCN family members suggest they have non-redundant roles. Using a positional-candidate approach, we found that mutations in the CCN family member WISP3 are associated with the autosomal recessive skeletal disorder progressive pseudorheumatoid dysplasia (PPD; MIM 208230). PPD is an autosomal recessive disorder that may be initially misdiagnosed as juvenile rheumatoid arthritis. Its population incidence has been estimated at 1 per million in the United Kingdom, but it is likely to be higher in the Middle East and Gulf States. Affected individuals are asymptomatic in early childhood. Signs and symptoms of disease typically develop between three and eight years of age. Clinically and radiographically, patients experience continued cartilage loss and destructive bone changes as they age, in several instances necessitating joint replacement surgery by the third decade of life. Extraskeletal manifestations have not been reported in PPD. Cartilage appears to be the primary affected tissue, and in one patient, a biopsy of the iliac crest revealed abnormal nests of chondrocytes and loss of normal cell columnar organization in growth zones. We have identified nine different WISP3 mutations in unrelated, affected individuals, indicating that the gene is essential for normal post-natal skeletal growth and cartilage homeostasis.

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confidence: 99%

Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia

et al. 1999

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“…Individuals with PPD appear normal at birth, have subtle clinical symptoms by 3 years of age, manifest radiologic changes of the axial and appendicular skeleton by 5 years of age, and develop severe degenerative joint disease necessitating joint replacement surgery by their second decade of life (5,21,24,27). Radiologically, in addition to platyspondyly, young patients with PPD have multiple sites of epiphyseal enlargement compared to age-and gender-matched controls (12,17). Histological examination shows that articular cartilage retrieved at the time of joint replacement surgery from patients with PPD is indistinguishable from that seen in common endstage osteoarthritis (W. Kutz et al, unpublished data).…”

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WISP3, the Gene Responsible for the Human Skeletal Disease Progressive Pseudorheumatoid Dysplasia, Is Not Essential for Skeletal Function in Mice

Kutz¹,

Gong²,

Warman

2005

Molecular and Cellular Biology

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In humans, loss-of-function mutations in WISP3 cause the autosomal recessive skeletal disease progressive pseudorheumatoid dysplasia (PPD) (Online Mendelian Inheritance in Man database number 208230). WISP3 encodes Wnt1-inducible signaling protein 3, a cysteine-rich, multidomain, secreted protein, whose paralogous CCN (connective tissue growth factor/cysteine-rich protein 61/nephroblastoma overexpressed) family members have been implicated in diverse biologic processes including skeletal, vascular, and neural development. To understand the role of WISP3 in the skeleton, we targeted the Wisp3 gene in mice by creating a mutant allele comparable to that which causes human disease. We also created transgenic mice that overexpress human WISP3 in cartilage. Surprisingly, homozygous Wisp3 mutant mice appear normal and do not recapitulate any of the morphological, radiographic, or histological abnormalities seen in patients with PPD. Mice that overexpress WISP3 are also normal. We conclude, that in contrast to humans, Wisp3 is not an essential participant during skeletal growth or homeostasis in mice.The CCN (connective tissue growth factor/cysteine-rich protein 61/nephroblastoma overexpressed) protein family comprises six cysteine-rich, multidomain-containing, secreted proteins (1,19,20). To date, only one CCN family member, Wnt1-inducible signaling protein 3 (WISP3/CCN6) has been associated with a human genetic disease. Mutations in WISP3 cause progressive pseudorheumatoid dysplasia (PPD) (4, 8), an autosomal recessive form of a spondyloepiphyseal dysplasia tarda. Individuals with PPD appear normal at birth, have subtle clinical symptoms by 3 years of age, manifest radiologic changes of the axial and appendicular skeleton by 5 years of age, and develop severe degenerative joint disease necessitating joint replacement surgery by their second decade of life (5,21,24,27). Radiologically, in addition to platyspondyly, young patients with PPD have multiple sites of epiphyseal enlargement compared to age-and gender-matched controls (12,17). Histological examination shows that articular cartilage retrieved at the time of joint replacement surgery from patients with PPD is indistinguishable from that seen in common endstage osteoarthritis (W. Kutz et al., unpublished data). Individuals with PPD have no organ involvement outside of their skeletal system. Consequently, in humans, the principal role of WISP3 appears to involve skeletal growth and cartilage homeostasis.We disrupted the Wisp3 gene in mice to create an animal model of Wisp3 deficiency and thus delineate the precise role of this protein in the skeleton. We found that homozygous Wisp3 mutant (Wisp3 Ϫ/Ϫ ) mice do not recapitulate any of the features that have been observed in patients with PPD. We also created transgenic mice that overexpress human WISP3 in cartilage; these mice are also normal. Our results suggest that although WISP3 is critical for normal skeletal function in humans, Wisp3 is not essential in mice. MATERIALS AND METHODS Construction of the Wisp3 tar...

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“…In the past, this disorder has been described under several synonyms, such as progressive pseudorheumatoid arthritis of childhood (PPAC) [2], and spondyloepiphyseal dysplasia tarda with progressive arthropathy [4,5], and progressive pseudorheumatoid arthritis [6].…”

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confidence: 99%

Progressive pseudorheumatoid dysplasia

et al. 2000

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A rare case of progressive pseudorheumatoid dysplasia (PPD) in a 9-year-old girl is presented. Clinically, chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties, were found. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and generalized platyspondyly with irregular delineation of the endplates of the vertebral bodies. The radioclinical features at the peripheral joints were originally misdiagnosed as juvenile rheumatoid arthritis (JRA), and the structural spinal abnormalities were neglected and interpreted as Scheuermann's disease. However, the absence of active inflammatory parameters argues against JRA, whereas the low age of onset of the irregularities at the vertebral endplates is an argument against the diagnosis of Scheuermann's disease. The combination of the dysplastic abnormalities of the spine, with platyspondyly and Scheuermann-like lesions at an unusually low age of onset, and radiological features mimicking JRA of the peripheral joints, is the clue to the diagnosis of this rare autosomal-recessive disease. This case is the first to document the MRI features of PPD of the spine.

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Radiographic Features of Progressive Pseudorheumatoid Arthritis

Cited by 20 publications

References 5 publications

Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia

Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia

WISP3, the Gene Responsible for the Human Skeletal Disease Progressive Pseudorheumatoid Dysplasia, Is Not Essential for Skeletal Function in Mice

Progressive pseudorheumatoid dysplasia

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