Comparison of orthopaedic manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study

Sang Gyo Seo,Chin Youb Chung,Hae-Ryong Song,Sung Sup Park,Won Joon Yoo,Changhoon Jeong,Ok-Hwa Kim,Hyun Woo Kim,Tae-Joon Cho,Jong Sup Shim,Chang-Wug Oh,Moon Seok Park,In Ho Choi,Kwang Soon Song

doi:10.1186/1471-2474-15-84

Abstract

BackgroundMultiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of the long bones. However, it is a genetically heterogeneous group of diseases sharing certain aspects of the radiologic phenotype. In surveys conducted in East Asia, MATN3 was the most common causative gene, followed by COMP. In this study, the authors compared clinical manifestation of MED patients caused by MATN3 and COMP gene mutations, as well as subsequent orthopaedic interventions.MethodsFifty nine molecularly-confirmed MED patients were subjects of this study. The MATN3 gene mutation group comprised of 37 patients (9 female, 28 male). The COMP gene mutation consisted of 22 cases (15 females, 7 males). Medical records and radiographs were reviewed, and questionnaire surveys or telephone interviews were conducted.ResultsAt the first presentation, the mean age was 8.8 ± 2.8 years (mean ± standard deviation) in the MATN3 group, and 8.5 ± 3.5 years in the COMP group (p = 0.670). The height in the COMP group was significantly shorter than those in the MATN3 group (p < 0.001). Gait abnormality at the first visit (p = 0.041) and the lastest follow-up (p = 0.037) were statistically significant difference. Hip pain (p = 0.084), limitation of daily activity (p = 0.075) at the latest follow-up tended to be more frequent in the COMP group. Hip dysplasia was more common in the COMP group, having significantly larger acetabular angle (p = 0.037), smaller center-edge angle (p = 0.002), severe Stulberg classification (p < 0.001), and smaller femoral head coverage (p < 0.001).ConclusionsClinical manifestations of MED caused by MATN3 were milder than manifestations of the COMP mutation group. These differences in clinical manifestation and prognosis justify molecular differentiation between the two genotypes.

Highlights

Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of long bones
Mutations of the gene encoding cartilage oligomeric matrix protein (COMP), matrilin-3 (MATN3), and alpha 1–3 chains of type IX collagen (COL9A1, COL9A2, COL9A3) are responsible for MED inherited as an autosomal dominant trait, [3] whereas mutations at the gene encoding diastrophic dysplasia sulfate transporter (DTDST or SLC26A2) are responsible for MED inherited as an autosomal recessive trait [4,5]
Subsequent studies reported that COMP (47% and 50%) was the most common causative gene followed by DTDST (25% and 28%), while MATN3 (17%) and COL9A1, 2, and 3 (8%) comprised only a small portion of these MED patients [3,9]

Summary

Introduction

Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of the long bones It is a genetically heterogeneous group of diseases sharing certain aspects of the radiologic phenotype. Subsequent studies reported that COMP (47% and 50%) was the most common causative gene followed by DTDST (25% and 28%), while MATN3 (17%) and COL9A1, 2, and 3 (8%) comprised only a small portion of these MED patients [3,9]. Studies on Korean [8] and Japanese [6] populations indicated that MATN3 was the most common causative gene, comprising 54.5% and 47.4% of MED patients with known genotype, followed by COMP mutations (41.8% and 36.8%, respectively). Type IX collagen genes and DTDST represented around 10% or less

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