Clinical features, molecular results, and management of 12 individuals with the rare arthrochalasia Ehlers-Danlos syndrome.
Adolescent
Adult
Child
Child, Preschool
Collagen Type I
/ genetics
Collagen Type I, alpha 1 Chain
Ehlers-Danlos Syndrome
/ epidemiology
Exons
/ genetics
Female
Genetic Predisposition to Disease
Hip Dislocation, Congenital
/ epidemiology
Humans
Male
Middle Aged
Mutation
/ genetics
Pedigree
Phenotype
Skin Abnormalities
/ genetics
Young Adult
COL1A1
COL1A2
Ehlers-Danlos syndrome (EDS)
arthrochalasia EDS
congenital hip dislocation
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
08
10
2019
revised:
22
12
2019
accepted:
28
01
2020
pubmed:
25
2
2020
medline:
13
1
2021
entrez:
25
2
2020
Statut:
ppublish
Résumé
Arthrochalasia Ehlers-Danlos syndrome (aEDS) is a rare autosomal dominant connective tissue disorder that is characterized by congenital bilateral hip dislocations, severe generalized joint hypermobility, recurrent joint (sub)luxations, and skin hyperextensibility. To date, 42 patients with aEDS have been published. We report 12 patients with aEDS from 10 families with 6 unpublished individuals and follow-up data on 6 adult patients. The clinical features are largely comparable with patients reported in the literature. Most (n = 10) patients had variants leading to (partial) loss of exon 6 of the COL1A1 or COL1A2 genes. One patient did not have a previously reported likely pathogenic COL1A1 variant. Data regarding management were retrieved. Hip surgery was performed in 5/12 patients and 3/12 patients underwent spinal surgery. As much as 4/12 patients were wheelchair-bound or unable to walk unaided. Fractures were present in 9/12 individuals with 1 patient requiring bisphosphonate treatment. Echocardiograms were performed in 10 patients and 2 individuals showed an abnormality likely unrelated to aEDS. One patient gave birth to two affected children and went through preterm labor requiring medication but had no additional complications. Of the eight adults in our cohort, the majority entered a career. Our data point toward a genotype-phenotype relationship with individuals with aEDS due to pathogenic COL1A1 variants causing complete or partial loss of exon 6 being more severely affected regarding musculoskeletal features. There is a significant lack of knowledge with regard to management of aEDS, particularly in adulthood. As such, systematic follow-up and multidisciplinary treatment is essential.
Identifiants
pubmed: 32091183
doi: 10.1002/ajmg.a.61523
doi:
Substances chimiques
COL1A2 protein, human
0
Collagen Type I
0
Collagen Type I, alpha 1 Chain
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
994-1007Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
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