Progressive Pseudorheumatoid Arthropathy Of Childhood

Watchlist

(log in to enable)

Retrieved

2021-01-23

Source

Orphanet

Trials

—

Genes

CCN6, SLC6A4, BDNF, ZRS, HP1BP3, LMBR1, HPD, AGO2, VSX1, SHH, TTC9B, ESR1, WNT1, C17orf97, POTEM, ZEB1, TNF, TPO, GALR2, POTEKP, PER2, ADIPOQ, FADS2, ATF7IP, FHL5, ACOT7, COA6, ACTBL2, PRL, GAL

CCN6, SLC6A4, BDNF, ZRS, HP1BP3, LMBR1, HPD, AGO2, VSX1, SHH, TTC9B, ESR1, WNT1, C17orf97, POTEM, ZEB1, TNF, TPO, GALR2, POTEKP, PER2, ADIPOQ, FADS2, ATF7IP, FHL5, ACOT7, COA6, ACTBL2, PRL, GAL, KRT20, SAGE1, SERPINA3, PIP, POMC, ACTG1, ACTG2, OPN1SW, TSPO, CDX2, CECR, COL2A1, COL10A1, COMT, CREB1, CRP, ESAT, ETV4, ETV5, GALR1, GLI1, GRIA1, NR3C1, HNRNPK, HSPA5, IFNG, IGF1, LEP, FADS1, NR3C2, MMP1, OXTR, CFP, RN7SL263P

Drugs

—

Interested in hearing about new therapies?

Progressive pseudorheumatoid arthropathy (dysplasia) of childhood (PPAC; PPD) presents as spondyloepiphyseal dysplasia (SED) tarda with progressive arthropathy and is described as a specific autosomal recessive subtype of SED.

Epidemiology

The prevalence has been estimated at 1/1,000,000 but it is likely to be higher in the Middle East and the Maghreb.

Clinical description

Most patients present the disease before the age of 8 years (the onset varies between 2 and 11 years). Typically, there are no symptoms in the newborn period. The most common signs at diagnosis are bowing of the legs, muscle weakness, symmetric swelling of the proximal interphalangeal joints. Motion range limitation, deformities and pain develop gradually, and spread to other joints. Many patients have spinal involvement manifesting as exaggerated lumbar lordosis, thoracic kyphosis, and/or scoliosis. Radiologically, the condition presents as SED with osteoporosis. The presence of an enlarged trigonium in the foot and synovial osteochondromatosis can be helpful for diagnosis. Extraskeletal manifestations (besides those secondary to the bony changes) have not been reported. Patients have normal facial appearance and intelligence.

Etiology

The responsible gene WISP3 (mapping to human chromosome 6q22) encodes a secreted growth regulator.

Diagnostic methods

Diagnosis is based on clinical and radiographic findings. Molecular testing is available on research basis.

Differential diagnosis

PPAC can be initially misdiagnosed as juvenile rheumatoid arthritis but is distinguished on radiographic analysis (especially the platyspondyly and generalised epiphyseal dysplasia) and the absence of inflammatory joint disease. PPAC must be differentiated from juvenile idiopathic arthritis to ensure optimal treatment and to avoid unnecessary exposure to immunosuppressants.

Antenatal diagnosis

As PPAC features are not present at birth, prenatal diagnosis based on clinical features is not possible.

Genetic counseling

PPAC is transmitted as an autosomal recessive trait.

Management and treatment

There is no specific treatment for PPAC. No clear prevention, improvement or slowing the disease course with anti-inflammatory drugs has been demonstrated.

Prognosis

PPAC does not affect life expectancy, but the progressive nature of the disease frequently requires joint replacement by early adulthood.