Progressive pseudorheumatoid dysplasia: a rare childhood disease

Torreggiani, Sofia; Torcoletti, Marta; Campos‐Xavier, Belinda; Baldo, Francesco; Agostoni, Carlo; Superti-Furga, Andrea; Filocamo, G

doi:10.1007/s00296-018-4170-6

Cited by 28 publications

(76 citation statements)

References 80 publications

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“…PPRD is due to a mutation in Wnt1-inducible signaling protein 3 (WISP3) gene, which encodes a signaling factor involved in cartilage homeostasis and bone growth by promoting type II collagen and aggrecan expression and regulating chondrocyte proliferation and differentiation 9 . WISP3 expression is decreased in PPRD articular chondrocytes (ACs).…”

Section: Discussionmentioning

confidence: 99%

“…PPRD is caused by mutations in the WISP3 gene which maps to chromosome 6q22, and encodes a protein in the connective tissue growth factor that is expressed in synoviocytes and chondrocytes involved in bone and cartilage growth and development 8 . Homozygous or compound heterozygous WISP3 mutations cause the loss of articular cartilage, which leads to the progressive narrowing of all articular spaces and reduced joint mobility 9 . While this molecular basis was elucidated over 10 years ago, no progress has been made towards a specific treatment for PPRD 2 .…”

Section: Introductionmentioning

confidence: 99%

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Systematical analysis of nine Chinese patients with progressive pseudorheumatoid dysplasia and assessment of calcitriol treatment

Li¹,

Mao²,

Zhou³

et al. 2020

Preprint

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Background: Progressive pseudorheumatoid dysplasia (PPRD) (MIM 208230) is a rare genetic disease characterized by progressive noninflammatory arthropathy affecting primarily the articular cartilage. Most patients are initially misdiagnosed because of the rarity of the disease and lack of awareness by most clinicians. Therefore, the purpose of the present study was to provide further diagnostic options to help clinicians make early precise diagnosis, and to investigate a new potential treatment for patients with PPRD. Methods: Clinical manifestations, radiographic features, Sanger Sequencing to determine WISP3 gene mutation and follow-up records were collected in 9 Chinese patients with PPRD. The time until diagnosis, relationship between clinical phenotypes and genotypes, and treatment effects were analyzed. Results: The clinical history and characteristics, mutations in the WISP3 gene, radiological data, treatment and outcome of 9 PPRD children were collected and reviewed. There were 3 pairs of siblings in this group and one patient had parental consanguinity. Five patients were misdiagnosed with juvenile idiopathic arthritis (JIA). The onset of disease in most patients (8/9) was between 3 and 6 years of age. The interval between onset of symptoms and obtaining the diagnosis for 8 of the patients varied between 3.6 years to 20 years. The onset of symptoms included enlarged and stiff interphalangeal joints of the fingers, gait disturbance or joint pain. Blood analysis revealed normal range of inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). Serum levels of 25-hydroxyvitamin D3 were analyzed in six patients and ranged from 6.16 to 22.1ng/ml, all lower than the normal range. Radiographic findings included different degree of abnormal vertebral bodies, epiphyseal enlargement of the interphalangeal joints with juxta-articular osteopenia, or reduction in hip articular space and cyst-like structures femoral head. A total of 7 variants in the WISP3 gene were identified in the 9 cases, presenting with three homozygous variants (c.397_404delCAAGTGTT, c.667T>G, and c.589+2T>C) and three compound heterozygous variants (c.589+2T>C/c.667T>G, c.624dupA/c.756C>A, and c.646T>C/c.1000T>C). After the treatment of calcitriol in the 6 patients with low level of 25-hydroxyvitamin D3 for 1.25 years to 1.75 years, two cases showed stable clinical disease activity and the other four patients joints’ pain and abnormal gait had improved. 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. The patients with PPRD having c.624dupA mutation in WISP3 may have delayed onset. Calcitriol showed treatment benefit by improving symptoms and decelerating progression of PPRD disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systematical analysis of nine Chinese patients with progressive pseudorheumatoid dysplasia and assessment of calcitriol treatment

Li¹,

Mao²,

Zhou³

et al. 2020

Preprint

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“…Diagnostic hand/feet radiographic finding is metaphyseal expansion of proximal phalanges [ Figure 11 ]. [ 21 ]…”

Section: Specific Disease Entitiesmentioning

confidence: 99%

Spine radiograph in dysplasias: A pictorial essay

Gabra

Jana

Naranje

et al. 2020

Indian Journal of Radiology and Imaging

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Spine radiograph is an essential component of a skeletal survey. It provides important diagnostic clues to various types of skeletal dysplasia. In some conditions, a spine radiograph alone may be diagnostic and characteristic; but mostly, it yields more value as a part of the complete skeletal survey. In this article we will discuss about a few common lethal and non-lethal skeletal dysplasias and their characteristic imaging findings; primarily focusing on the spine radiograph.

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“…The clinical, radiological, and histological features of SED‐S overlap with those of other skeletal dysplasias such as progressive pseudorheumatoid dysplasia (PPRD, MIM 208230), other type II collagenopathies, type XI collagenopathies, or unclassifiable SED (Deng, Huang, & Yuan, 2016; Hurvitz et al, 1999; Spranger, 1998; Torreggiani et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Spondyloepiphyseal dysplasia type Stanescu: Expanding the clinical and molecular spectrum of a very rare type II collagenopathy

Travessa

Díaz‐González

Mirco

et al. 2020

American J of Med Genetics Pt A

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Spondyloepiphyseal dysplasia type Stanescu (SED-S) is a very rare type II collagenopathy. We describe an 8-year-old boy who presented with short trunk, C2-C3 vertebral fusion, hand, foot, leg and thigh pain, stiffness and limited joint mobility, and waddling gait. Radiographs showed platyspondyly with anterior wedging and endplate irregularities, broad femoral necks, and large epiphyses and epiphyseal equivalents. Differential diagnosis included progressive pseudorheumatoid dysplasia and SED-S. A skeletal dysplasia custom-designed NGS panel was performed and the heterozygous pathogenic variant c.620G>A; p.(Gly207Glu) in COL2A1 was detected, establishing the diagnosis of SED-S. Vertebral fusions, observed in our patient, have not been previously described in this dysplasia. This variant has not been previously associated with SED-S, but was reported in two other families with spondyloepiphyseal dysplasia. Thus, this case expands the clinical and mutational spectrum of SED-S and demonstrates that SED-S significantly overlaps with other skeletal dysplasias.

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Progressive pseudorheumatoid dysplasia: a rare childhood disease

Cited by 28 publications

References 80 publications

Systematical analysis of nine Chinese patients with progressive pseudorheumatoid dysplasia and assessment of calcitriol treatment

Systematical analysis of nine Chinese patients with progressive pseudorheumatoid dysplasia and assessment of calcitriol treatment

Spine radiograph in dysplasias: A pictorial essay

Spondyloepiphyseal dysplasia type Stanescu: Expanding the clinical and molecular spectrum of a very rare type II collagenopathy

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