Clinical features, molecular results, and management of 12 individuals with the rare arthrochalasia Ehlers‐Danlos syndrome

Abstract

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 We report 12 patients with aEDS from 10 families with 6 unpublished individuals and follow-up data on 6 adult patients.The clinical features are largely comparable with patients reported in the literature.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. K E Y W O R D S arthrochalasia EDS, COL1A1, COL1A2, congenital hip dislocation, Ehlers-Danlos syndrome (EDS)

Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives

“…Our results partly support the still controversial impression that bone quality might be impaired in cEDS [74][75][76][77][78], although undoubtfully less significant compared to other EDS subtypes (e.g. spondylodysplastic, arthrochalasia, kyphoscoliotic, and classical-like type 2 EDS) [9,43,44,48,49,52,59,65,68] or skeletal dysplasia [39], and suggests a potential involvement of skeletal fragility in determining a poorer quality of life (QoL) in adult patients. Our findings emphasize a milder phenotype and disease course in cEDS compared to hEDS [50,69] and other EDS subtypes (e.g.…”

“…The clEDS type 1 is generally distinguishable from cEDS for the absence of atrophic scarring [28,45,[53][54][55][56][57], whereas a more severe multisystemic presentation in clEDS type 2 should assist the differential diagnosis with cEDS [43,52,[58][59][60]. The dermatosparaxis (ADAMTS2) [61], cardiac-valvular (COL1A2) [62][63][64], kyphoscoliotic (PLOD1, FKBP14) [65,66], and arthrochalasia (COL1A1, COL1A2) [67,68] EDS subtypes, also sharing with cEDS several cutaneous and articular issues, are mostly distinguishable for the presence of specific hallmarks [1,9,16].…”

Ehlers–Danlos Syndrome Type Arthrochalasia: A Systematic Review

“…In addition to the characteristic clinical manifestations of the disease, less prevalent manifestations are observed in the cases described. The most notable are those cited by Ayoub et al [20], such as muscular hypotonia, kyphoscoliosis, radiologically mild osteopenia, tissue fragility, including atrophic scarring, and hematomas.…”

“…Ayoub et al [20], Brady et al [18], Hakim et al [13], and Giunta et al [1] describe aEDS as a rare autosomal dominant connective tissue disorder, which is characterized by clinical manifestations such as congenital bilateral hip dislocation, severe generalized hypermobility of articulations, recurrent articular dislocations and subluxations, and hyperextensibility of the dermis.…”

“…The results of the studies reviewed indicate that there is still no curative treatment for aEDS [20].…”