Table 1.

Villefranche criteria for the six major subtypes of Ehlers-Danlos syndrome

Common variant	Inheritance	Causative gene(s)	Major criteria	Minor criteria
Classic	AD	COL5A1, COL5A2	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	AD	Mostly unknown	Hyperextensible and/or Smooth, velvety skin Generalized joint hypermobility	Recurring joint dislocations Chronic joint/limb pain Positive family history
Vascular	AD	COL3A1	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	AR	PLOD1	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	AD	COL1A1, COL1A2	Generalized joint hypermobility with recurrent subluxations Congenital bilateral hip dislocation	Skin hyperextensibility Tissue fragility, including atrophic scars Easy bruising Hypotonia Kyphoscoliosis Osteopenia/porosis
Dermatosparaxis	AR	ADAMTS2	Severe skin fragility Sagging, redundant skin	Soft, doughy skin texture Easy bruising Premature rupture of fetal membranes Large hernias (umbilical, inguinal)

AD: Autosomal dominant; AR: Autosomal recessive; EDS: Ehlers-Danlos syndrome. No clear indication for using these criteria in the establishment of a firm clinical suspect of a specific EDS subtype is specified. However, the presence of at least 1 major and 1 minor criteria is usually necessary for proceeding in molecular confirmation of EDS 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. Adapted from Beighton et al.³