Arthrochalasia Ehlers-Danlos Syndrome


A form of Ehlers-Danlos syndrome (EDS) characterized by congenital bilateral hip dislocation, severe generalized joint hypermobility with recurrent joint dislocations and subluxations, hyperextensible and/or fragile skin.


The exact prevalence is unknown. It is one of the rare types of EDS.

Clinical description

Patients affected by arthrochalasia Ehlers-Danlos syndrome (aEDS) present at birth with severe hypermobility of both small and large joints with easy dislocation on manipulation, in combination with muscular hypotonia. Congenital bilateral hip dislocation is present in virtually all cases, and congenital foot deformities (clubfoot, flat foot and skew foot) and other congenital joint subluxations/luxations are common. Skin is hyperextensible and described as hyperelastic/redundant, leading sometimes to a criss-cross crease patterning of the palms and soles. Easy bruising and atrophic scarring may also be present, but are not severe. Hypotonia improves with age but, in combination with foot deformities and instable knees, leads to a delay in acquisition of gross motor milestones. Craniofacial dysmorphism is usually mild and may include large fontanelle, frontal bossing, hypertelorism, blue sclera, depressed nasal bridge, midface hypoplasia, and micrognathia. Throughout life, patients suffer recurrent partial or total joint dislocations of upper and lower limb joints and develop persistent foot, hand and spinal deformities. Some patients may also display bone fragility, manifested with fractures, Wormian bones on cranial radiographs, and osteopenia. Dentinogenesis imperfecta has been reported only in few individuals.


aEDS is caused by heterozygous mutations that lead to partial or total loss of exon 6 in the COL1A1 (17q21.33) or COL1A2 (7q21.3) genes. The mutations lead to the partial or complete loss of the N-telopeptide of the procollagen type I alpha1 and alpha2 chains, respectively, and result in accumulation of abnormally processed type I collagen, the principal component of ligaments, tendons, dermis, bone and dentin.

Diagnostic methods

Clinical diagnosis is confirmed by the biochemical study of collagen I produced in vitro by cultured skin fibroblasts, or by molecular analysis revealing pathogenic variants in the COL1A1 or COL1A2 genes.

Differential diagnosis

Differential diagnosis includes Larsen syndrome, classical EDS (cEDS), dermatosparaxis EDS (dEDS), kyphoscoliotic EDS (kEDS) and musculocontractural EDS (mcEDS), Loeys-Dietz syndrome and autosomal recessive cutis laxa type 2B.

Antenatal diagnosis

Prenatal testing by molecular or biochemical analyses of a chorionic villus biopsy is possible if a pathogenic mutation has been identified in the family or, if parental mosaicism is suspected. Joint dislocations can be observed on prenatal ultrasound examination (in the third trimester of pregnancy).

Genetic counseling

The pattern of inheritance is autosomal dominant. Genetic counseling can inform parents of an affected child of the 50% risk of disease recurrence among future offspring. Clinically mild or unrecognized parental mosaicism has to be taken into account. Specific heterozygous mutations in COL1A1, c.472-1G>A and c.472-2A>T, have been associated with dentinogenesis imperfecta.

Management and treatment

Management of orthopedic problems is the center of care for patients with aEDS, with the goal being to achieve stable ambulation. A complete skeletal survey is recommended at diagnosis. Open reductions with an iliac osteotomy, with or without femoral osteotomy, are favorable to treat congenital hip dislocations. Orthotic management and early intervention are recommended to assist standing, walking and activities of daily living.


Extensive management seems to be effective, since only few patients described in the literature, mainly those with mutations in COL1A1, are wheelchair bound or unable to walk independently. aEDS patients are at increased risk of premature osteoarthritis.