El-Lababidi Nabil, Zikánová Marie, Baxová Alice, Nosková Lenka, Leiská Alena, Lambert Lukáš, Honzík Tomáš, Zeman Jiří
Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Prague Med Rep. 2020;121(3):153-162. doi: 10.14712/23362936.2020.14.
Dominantly inherited mutations in COMP gene encoding cartilage oligomeric matrix protein may cause two dwarfing skeletal dysplasias, milder multiple epiphyseal dysplasia (MED) and more severe pseudoachondroplasia (PSACH). We studied the phenotype and X-rays of 11 patients from 5 unrelated families with different COMP mutations. Whole exome and/or Sangers sequencing were used for molecular analyses. Four to ten X-ray images of hands hips, knees or spine were available for each patient for retrospective analyses. Eight patients with MED have mutation c.1220G>A and 3 children with PSACH mutations c.1359C>A, c.1336G>A, or the novel mutation c.1126G>T in COMP. Progressive failure in growth developed in all patients from early childhood and resulted in short stature < 3rd percentile in 7 patients and very short stature < 1st percentile in four. Most patients had joint pain since childhood, severe stiffness in shoulders and elbows but increased mobility in wrists. Six children had bowlegs and two had knock knees. In all patients, X-rays of hands, hips and knees showed progressive, age-dependent skeletal involvement more pronounced in the epiphyses of long rather than short tubular bones. Anterior elongation and biconvex configuration of vertebral bodies were more conspicuous for kids. Six children had correction of knees and two adults had hip replacement. Skeletal and joint impairment in patients with MED and PSACH due to COMP mutation start in early childhood. Although the clinical severity is mutation and age dependent, many symptoms represent a continuous phenotypic spectrum between both diseases. Most patients may benefit from orthopaedic surgeries.
编码软骨寡聚基质蛋白的COMP基因的显性遗传突变可能导致两种侏儒性骨骼发育不良，症状较轻的多发性骨骺发育不良（MED）和更严重的假性软骨发育不全（PSACH）。我们研究了来自5个无关家庭的11名具有不同COMP突变患者的表型和X线表现。采用全外显子组测序和/或桑格测序进行分子分析。每位患者有4至10张手部、髋部、膝部或脊柱的X线图像用于回顾性分析。8例MED患者有c.1220G＞A突变，3例PSACH患儿有COMP基因的c.1359C＞A、c.1336G＞A或新突变c.1126G＞T。所有患者从幼儿期开始就出现进行性生长发育迟缓，7例患者身高低于第3百分位数，4例患者身高极低，低于第1百分位数。大多数患者自幼就有关节疼痛，肩部和肘部严重僵硬，但腕部活动度增加。6名儿童有膝内翻，2名有膝外翻。在所有患者中，手部、髋部和膝部的X线显示出进行性的、与年龄相关的骨骼受累，在长管状骨而非短管状骨的骨骺中更为明显。椎体的前部延长和双凸形态在儿童中更为明显。6名儿童进行了膝关节矫正，2名成人进行了髋关节置换。由于COMP突变导致的MED和PSACH患者的骨骼和关节损伤始于幼儿期。虽然临床严重程度取决于突变和年龄，但许多症状代表了这两种疾病之间连续的表型谱。大多数患者可能从骨科手术中获益。
