Ehlers-Danlos Syndrome, Hypermobility Type

Description

The Ehlers-Danlos syndrome shows phenotypic and genetic heterogeneity; see 130000. Marked joint hyperextensibility without skeletal deformity dominates the clinical picture of hypermobility-type EDS. Skin manifestations are relatively inconspicuous. Differentiation from familial joint laxity (147900) is often uncertain.

Clinical Features

Wenstrup et al. (2002) performed a prospective cohort study on 71 consecutive EDS patients. Twenty of 71, or 28%, had aortic root dilatation defined as greater than 2 serum deviations above population-based norms. Fourteen of 42 individuals with the classic form of EDS (see 130000) and 6 of 29 individuals with the hypermobile form had aortic root dilatation, with no gender differences. Wenstrup et al. (2002) concluded that aortic root dilatation is a common finding in EDS. However, rates of progression and complication were unknown.

Castori et al. (2010) noted that there are more female than male patients with signs and symptoms of joint hypermobility. In a cohort of 38 well-characterized EDS hypermobility type index cases, 34 (89%) were female and 4 (11%) male. A positive family history was found for 9 probands, and among the affected relatives, 9 were female (69%) and 4 were male (31%), yielding a F:M sex ratio of 43 (84%): 8 (16%). Castori et al. (2010) postulated different mechanisms for the sex bias, including differential perception of muscle pain between men and women, greater joint stability in men, and hormonal changes in women. All of these biologic factors may work to explain the high gender bias in this disorder.

Other Features

Voermans et al. (2009) performed a cross-sectional study on the presence of neuromuscular symptoms among 40 patients with various forms of EDS. Ten patients each were analyzed with classic EDS (130000), vascular EDS (130050), hypermobility EDS, and TNX-deficient EDS (606408). Overall, those with classic EDS and TNX-deficient EDS reported the most neuromuscular involvement, with muscle weakness, hypotonia, myalgia, easy fatigability, and intermittent paresthesias, although patients in all groups reported these features. Physical examination showed mild to moderate muscle weakness (85%) and reduction of vibration sense (60%) across all groups. Nerve conduction studies demonstrated axonal polyneuropathy in 5 (13%) of 39 patients. Needle electromyography showed myopathic EMG features in 9 (26%) and a mixed neurogenic-myopathic pattern in 21 (60%) of 35 patients. Muscle ultrasound showed increased echo intensity in 19 (48%) and atrophy in 20 (50%) of 40 patients. Mild myopathic features were seen on muscle biopsy of 5 (28%) of 18 patients. Patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. Voermans et al. (2009) postulated that abnormalities in muscle or nerve extracellular matrix may underlie these findings.

Molecular Genetics

Narcisi et al. (1994) reported a family in which multiple members with a connective tissue disorder answering to the description of either EDS III or familial joint instability syndrome (147900) had a mutation in the COL3A1 gene (G637S; 120180.0020). Abnormalities in type III collagen are characteristic of EDS IV (130050); no features of that disorder, such as thin skin, typical facial features, or vascular fragility, were found in affected members of the family. The disorder in this family is here classified as a nonvascular variant of EDS IV.