Management of progressive spine deformity in a child with pseudoachondroplasia

Short-limbed dwarfism, knock knees and joint hypermobility are the classical clinical criteria encountered in patients with pseudoachondroplasia. Progressive kyphoscoliosis was the main clinical presentation in our patients with pseudoachondroplasia. Preoperative spine radiographs in an 13-years-old-girl showed severe kyphoscoliotic deformity (kyphosis - 70o and scoliosis of Cobbs angle – 55o ). Keywords: Pseudoachondroplasia; COMP gene mutation.

A novel COMP Mutation in a Chinese Family with Multiple Epiphyseal Dysplasia

Background: Multiple Epiphyseal Dysplasia (MED) is a skeletal disorder characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis, at least 66% of the reported autosomal dominant MED (AD-MED) cases are caused by COMP mutations. Methods : Here, we reported a four-generation Chinese family with early-onset hip osteoarthritis, flatfoot, brachydactyly, and mild short stature. Whole exome sequencing was performed on the proband followed by enquiring family history, detailed physical examination, and radiographic evaluation. After that, the pathogenicity of candidate mutation was also analyzed. Results : We recruited a dominant MED family with 10 affected members and 17 unaffected members. The main radiographic findings were symmetric changes in dysplastic acetabulum and femoral head, irregular contours of epiphyses, shorted femoral neck, and flatfoot. Lower bone density of ankle joint , wrist joint, and knees were observed as well as irregular vertebral end plates. As a result, we found a missense mutation c.1153G>T (p. Asp385Tyr) located in the exon 11 of COMP gene. This mutation was assessed as “pathogenic” for the low allele frequency and a high likelihood of co-segregation with disease in the reported family. Sanger sequencing identified a novel heterozygous mutation c.1153G>T (p. Asp385Tyr), in exon 11 of COMP gene in all affected male individuals. Conclusions: Our result underlined the key role for Asp385 amino acid in the protein function of COMP, and first confirmed the pathogenicity of COMP (c.1153G>T; p. Asp385Tyr) in AD-MED disease. We expanded the mutational spectrum of COMP and phenotypic information of AD-MED.

Orthopaedic manifestations of pseudoachondroplasia

Purpose In 1959, Maroteaux and Lamy initially designated pseudoachondroplasia as a distinct dysplasia different from achondroplasia the most common form of skeletal dysplasia. Pseudoachondroplasia is caused by a mutation in the collagen oligomeric matrix protein gene (COMP) gene on chromosome 19p13.1-p12 encoding the COMP. The COMP gene mutations result in rendering the articular and growth plate cartilages incapable of withstanding routine biomechanical loads with resultant deformity of the joints. The purpose of the study was to characterize the typical orthopaedic findings in pseudoachondroplasia. Methods The charts and radiographs of 141 patients with pseudoachondroplasia were analyzed. This cohort, to our knowledge, represents the largest group of patients describing the typical orthopaedic manifestations of pseudoachondroplasia. Results Patients with pseudoachondroplasia have normal craniofacial appearance with normal intelligence. Short stature is not present at birth and generally appears by two to four years of age. The condition is a form of spondyloepiphyseal dysplasia and the long bones are characterized by dysplastic changes in the epiphysis, metaphysis and vertebral bodies. Radiographically the long bones have altered the appearance and structure of the epiphyses with small irregularly formed or fragmented epiphyses or flattening. The metaphyseal regions of the long bones show flaring, widening or ‘trumpeting’. The cervical (89%) and thoracic and lumbar vertebrae show either platyspondyly, ovoid, ‘cod-fish’ deformity or anterior ‘beaking’. Kyphosis (28%), scoliosis (58%) and lumbar lordosis (100%) are commonly seen. The femoral head and acetabulum are severely dysplastic (100%). The knees show either genu valgum (22%), genu varum (56%) or ‘windswept’ deformity (22%). Conclusion Most commonly these distortions of the appendicular and the axial skeleton lead to premature arthritis particularly of the hips and often the knees not uncommonly in the 20- to 30-year-old age group. Level of Evidence: III