Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

Table 2

The Villefranche criteria for major EDS subtypes.

Subtype	Major criteria	Minor criteria
Classic	Skin hyperextensibility; Widened atrophic scars; Joint hypermobility	Smooth, velvety skin; Molluscoid pseudotumors; Subcutaneous spheroids; Complications of joint hypermobility; Muscle hypotonia, motor delay; Easy bruising; Manifestations of tissue extensibility and fragility; Surgical complications; Positive family history
Hypermobility	Hyperextensible and/or smooth, velvety skin; Generalized joint hypermobility	Recurring joint dislocations; Chronic joint/limb pain; Positive family history
Vascular	Thin, translucent skin; Arterial/intestinal/uterine fragility or rupture; Extensive bruising; Characteristic facial appearance	Acrogeria; Hypermobility of small joints; Tendon and muscle rupture; Talipes equinovarus; Early-onset varicose veins; Arteriovenous, carotid-cavernous sinus fistula; Pneumothorax/pneumohemothorax; Gingival recessions; Positive family history, sudden death in a close relative
Kyphoscoliotic	Generalized joint hypermobility; Congenital hypotonia; Congenital and progressive scoliosis; Scleral fragility and rupture of the ocular globe	Tissue fragility, including atrophic scars; Easy bruising; Arterial rupture; Marfanoid habitus; Microcornea; Osteopenia/porosis; Positive family history
Arthrochalasis	Generalized joint hypermobility with recurrent subluxations; Congenital bilateral hip dislocation	Skin hyperextensibility; Tissue fragility, including atrophic scars; Easy bruising; Hypotonia; Kyphoscoliosis; Osteopenia/porosis
Dermatosparaxis	Severe skin fragility; Sagging, redundant skin	Soft, doughy skin texture; Easy bruising; Premature rupture of fetal membranes; Large hernias (umbilical, inguinal)

Adapted from [4].
Note 1: no clear indication for using these criteria in the establishment of a firm clinical suspect of a specific Ehlers-Danlos syndrome subtype is specified. However, the presence of at least 1 major and 1 minor criteria is usually necessary for proceeding in molecular confirmation of Ehlers-Danlos syndrome subtypes with a known, prevalent molecular cause. The presence of at least two major criteria is strongly indicative for a definite diagnosis of the specific EDS subtype.