Multiple disc herniation in spondyloepiphyseal dysplasia tarda: A rare case report and review of the literature.

BACKGROUND: Spondyloepiphyseal dysplasia tarda (SEDT) is a rare, hereditary, X-linked skeletal disorder. To our knowledge, there are few reports about orthopedic surgery in these patients. This is the first report on patients with SEDT undergoing spinal and fracture reduction surgery. CASE PRESENTATION: A 31-year-old male patient who had been misdiagnosed with juvenile idiopathic arthritis (JIA) for 20 years and who had been treated with femoral shaft internal fixation for lower extremity fracture caused by minor trauma presented at hospital with stiffness and weakness in the lower extremities for the past two years. Radiographs showed bony dysplastic features of flattened vertebral bodies, Scheuermann-like changes in the spine, and osteoarthritis-like changes in the joints. Laboratory examination, including routine blood tests and rheumatism-related indicators showed negative results. Considering the history, radiology, and genetic findings, a diagnosis of spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) was considered. Further neurological examination indicated that severe spinal cord compression was an important reason for the patient's inability to walk. Laminectomy, spinal canal decompression, internal fixation and fusion were performed. Clinical outcome was satisfactory at one-year follow-up. The lower-limb fatigue was relieved, the patient could walk independently, and his examination showed osseous fusion. The English database was searched and the literature was reviewed for the relevant keywords of "SEDT-PA". CONCLUSIONS: Progress has been made in genetic research on SEDT; early diagnosis is particularly important, but the clinical diagnosis and treatment plans are still evaluated on a case-by-case basis. The best treatment for SEDT is to identify patients with progressive neurological and joint-mobility impairments and perform appropriate surgical intervention. Surgical intervention can improve neurological function and quality of life. However, surgery, as palliative care, does not alter the progression of the disease.

Progressive pseudorheumatoid dysplasia: a rare childhood disease.

Progressive pseudorheumatoid dysplasia (PPRD) is a genetic bone disorder characterised by the progressive degeneration of articular cartilage that leads to pain, stiffness and joint enlargement. As PPRD is a rare disease, available literature is mainly represented by single case reports and only a few larger case series. Our aim is to review the literature concerning clinical, laboratory and radiological features of PPRD. PPRD is due to a mutation in Wnt1-inducible signalling protein 3 (WISP3) gene, which encodes a signalling factor involved in cartilage homeostasis. The disease onset in childhood and skeletal changes progresses over time leading to significant disability. PPRD is a rare condition that should be suspected if a child develops symmetrical polyarticular involvement without systemic inflammation, knobbly interphalangeal joints of the hands, and gait abnormalities. A full skeletal survey, or at least a lateral radiograph of the spine, can direct towards a correct diagnosis that can be confirmed molecularly. More than 70 WISP3 mutations have so far been reported. Genetic testing should start with the study of genomic DNA extracted from blood leucocytes, but intronic mutations in WISP3 causing splicing aberrations can only be detected by analysing WISP3 mRNA, which can be extracted from cultured skin fibroblasts. A skin biopsy is, therefore, indicated in patients with typical PPRD findings and negative mutation screening of genomic DNA.

Novel COL2A1 variant (c.619G>A, p.Gly207Arg) manifesting as a phenotype similar to progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia, Stanescu type.

Progressive pseudorheumatoid dysplasia (PPRD) is a rare, autosomal-recessive condition characterized by mild spondyloepiphyseal dysplasia (SED) and severe, progressive, early-onset arthritis due to WISP3 mutations. SED, Stanescu type, is a vaguely delineated autosomal-dominant dysplasia of unknown genetic etiology. Here, we report three individuals from two unrelated families with radiological features similar to PPRD and SED, Stanescu type who share the same novel COL2A1 variant and were matched following discussion at an academic conference. In the first family, we performed whole-exome sequencing on three family members, two of whom have a PPRD-like phenotype, and identified a heterozygous variant (c.619G>A, p.Gly207Arg) in both affected individuals. Independently, targeted sequencing of the COL2A1 gene in an unrelated proband with a similar phenotype identified the same heterozygous variant. We suggest that the p.Gly207Arg variant causes a distinct type II collagenopathy with features of PPRD and SED, Stanescu type.

Novel WISP3 mutations causing spondyloepiphyseal dysplasia tarda with progressive arthropathy in two unrelated Chinese families.

Spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) is an autosomal recessive skeletal disorder resulting from pathogenic mutations in the Wnt1-inducible signaling pathway protein 3 (WISP3) gene. This disorder predominantly involves the skeletal system, with the leading features of platyspondyly, metaphyseal dysplasia of limbs and extremities, and progressive degeneration of joints. To date, 53 distinct forms of WISP3 mutations have been detected globally, eleven of which originated from Chinese patients. In the current study, we reported the clinical manifestations and radiographic features of two unrelated Chinese SEDT-PA patients. Through genetic analysis, two novel mutations (c.624delA, c.105dupT) as well as one recurrent mutation (c.342T>G) were identified in the WISP3 gene. Our study contributed to the further expansion of the WISP3 mutation spectrum, and demonstrated the genotype-phenotype relationship between mutations in the WISP3 gene and clinical findings of SEDT-PA.