Early severe scoliosis in a patient with atypical progressive pseudorheumatoid dysplasia (PPD): Identification of two WISP3 mutations, one previously unreported

Abstract

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive disorder characterized by spondyloepiphyseal dysplasia associated with pain and stiffness of multiple joints, enlargement of the interphalangeal joints, normal inflammatory parameters, and absence of extra-skeletal manifestations. Homozygous or compound heterozygous WISP3 mutations cause PPD. We report two siblings from a non-consanguineous Ecuadorian family with a late-onset spondyloepiphyseal dysplasia. Mutation screening was undertaken in the two affected siblings using a customized skeletal dysplasia next generation sequencing (NGS) panel and confirmed by Sanger sequencing. Two compound heterozygous mutations were identified in WISP3 exon 2, c.[190G>A];[197G>A] (p.[(Gly64Arg)];[(Ser66Asn)]) in the two siblings, both of which had been inherited. The p. (Gly64Arg) mutation has not been previously described whilst the p. (Ser66Asn) mutation has been reported in two PPD families. The two siblings presented with atypical PPD, as they presented during late childhood, yet the severity was different between them. The progression was particularly aggressive in the male sibling who suffered severe scoliosis by the age of 13 years. This case reaffirms the clinical heterogeneity of this disorder and the clinical utility of NGS to genetically diagnose skeletal dysplasias, enabling adequate management, monitorization, and genetic counseling. © 2016 Wiley Periodicals, Inc.

Pain evaluation in a sample of Turkish children with cerebral palsy and its association with dependency level, verbal abilities, and the quality of life of patients and sociodemographic status, depression, and quality of life of their caregivers

“…Missing values were handled by removing the missing items from the calculation, provided that no more than half of the items from any domain were incomplete. [17] The CPCHILD can be calculated practically using the excel calculation program, [18] and it has been found that the validity and reliability of CP are high. [14] In the present study, we evaluated pain using the NCCPC-R results (≥7 painful and <7 painless) and the CPCHILD comfort and emotions subscale scores.…”

Progressive pseudorheumatoid dysplasia with new-found gene mutation of Wntl inducible signaling pathway protein 3

“…Patients with PPD also have spinal lesion, but no clinical appearance at early stage. Patients older than 15 years begin to have lumbar lordosis, thoracic kyphosis, spinal scoliosis and bow-backed deformation [ 10 ]. Not only thickening of ligamentum flavum and posterior longitudinal ligament, but also protrusion of intervertebral disc lead to spinal canal stenosis and spinal nerve compression.…”

Progressive pseudorheumatoid dysplasia: a case series report

“…The main clinical manifestations are premature degenerative changes of articular cartilage, progressive articular stiffness, articular bulge, deformity, and limited activity. The disease is often asymptomatic in early childhood, with typical symptoms occurring at ages 3 to 8 years (2). The small joints of both the hands and lower limbs are the most affected, and the peripheral joints that are often affected are the small joints of the hand, hip, elbow, knee, wrist, shoulder, ankle and foot.…”