Prague Med. Rep. 2020, 121, 153-162

https://doi.org/10.14712/23362936.2020.14

Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene

Nabil El-Lababidi1, Marie Zikánová1, Alice Baxová2, Lenka Nosková1, Alena Leiská3, Lukáš Lambert3, Tomáš Honzík1, Jiří Zeman1

1Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
2Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
3Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

Received April 13, 2020
Accepted September 14, 2020

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.

Funding

This study was supported by projects Progres Q32, RVO VFN 64165 and PRIMUS/17/MED/6.

References

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