Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene
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 w...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Karolinum Press
2020-10-01
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| Series: | Prague Medical Report |
| Subjects: | |
| Online Access: | https://pmr.lf1.cuni.cz/121/3/0153/ |
| _version_ | 1818416804730503168 |
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| author | Nabil El-Lababidi Marie Zikánová Alice Baxová Lenka Nosková Alena Leiská Lukáš Lambert Tomáš Honzík Jiří Zeman |
| author_facet | Nabil El-Lababidi Marie Zikánová Alice Baxová Lenka Nosková Alena Leiská Lukáš Lambert Tomáš Honzík Jiří Zeman |
| author_sort | Nabil El-Lababidi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T11:56:43Z |
| format | Article |
| id | doaj.art-d450c9a33fe74e548b3b0623d87dfce2 |
| institution | Directory Open Access Journal |
| issn | 1214-6994 2336-2936 |
| language | English |
| last_indexed | 2024-12-14T11:56:43Z |
| publishDate | 2020-10-01 |
| publisher | Karolinum Press |
| record_format | Article |
| series | Prague Medical Report |
| spelling | doaj.art-d450c9a33fe74e548b3b0623d87dfce22022-12-21T23:02:06ZengKarolinum PressPrague Medical Report1214-69942336-29362020-10-01121315316210.14712/23362936.2020.1410403Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP GeneNabil El-LababidiMarie ZikánováAlice BaxováLenka NoskováAlena LeiskáLukáš LambertTomáš HonzíkJiří ZemanDominantly 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.https://pmr.lf1.cuni.cz/121/3/0153/short staturemultiple epiphyseal dysplasiapseudoachondroplasiacomp |
| spellingShingle | Nabil El-Lababidi Marie Zikánová Alice Baxová Lenka Nosková Alena Leiská Lukáš Lambert Tomáš Honzík Jiří Zeman Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene Prague Medical Report short stature multiple epiphyseal dysplasia pseudoachondroplasia comp |
| title | Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene |
| title_full | Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene |
| title_fullStr | Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene |
| title_full_unstemmed | Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene |
| title_short | Age Dependent Progression of Multiple Epiphyseal Dysplasia and Pseudoachondroplasia Due to Heterozygous Mutations in COMP Gene |
| title_sort | age dependent progression of multiple epiphyseal dysplasia and pseudoachondroplasia due to heterozygous mutations in comp gene |
| topic | short stature multiple epiphyseal dysplasia pseudoachondroplasia comp |
| url | https://pmr.lf1.cuni.cz/121/3/0153/ |
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