Table 3.

Ehlers-Danlos Syndromes classification (adapted from Beighton P et al. [21])

Type	Clinical manifestations		IPa	Protein	Gene
	Major criteria	Minor criteria
Classic (type I/II)	Skin hyperextensibility	Easy bruising	AD	Type V procollagen (~50 %)	COL5A1
	Widened atrophic scarring	Molluscoid pseudotumors			COL5A2
	Joint hypermobility	Subcutaneous spheroids
	Smooth and velvety skin	Muscular hypotonia
		Complications of joint hypermobility
		Surgical complications
		Positive family history
Hypermobility (type III)	Generalized joint hypermobility mild skin involvement	Recurring joint dislocations	AD	Tenascin X (~5 %)	TNX-B
		Chronic joint pain
		Positive family history
Vascular (type IV)	Excessive bruising	Acrogeria	AD	Type III procollagen	COL3A1
	Thin, translucent skin	Early-onset varicose veins
	Arterial/intestinal/uterine fragility or rupture	Hypermobility of small joints
	Characteristic facial appearance	Tendon and muscle rupture
		Arteriovenous or carotid-cavernous sinus fistula
		Pneumo (hemo)thorax
		Positive family history, sudden death in close relative(s)
Kyphoscoliotic (type VI)	Severe muscular hypotonia at birth	Tissue fragility, including atrophic scars	AR	Type VIA: Lysyl hydroxylase 1	LH-1 (PLOD1)
	Generalized joint laxity	Easy bruising
	Kyphoscoliosis at birth	Arterial rupture
	Scleral fragility and rupture of the globe	Marfanoid habitus		Type VIB: not known
		Microcornea
		Osteopenia
Arthrochalasis (type VII A & B)	Severe generalized joint hypermobility with recurrent subluxations	Skin hyperextensibility	AD	Type I procollagen	COL1A1
	Congenital bilateral hip dislocation	Tissue fragility, including atrophic scars			COL1A2
		Easy bruising
		Muscular hypotonia
		Kyphoscoliois
		Mild osteopenia
Dermatosparaxis (type VII C)	Severe skin fragility	Soft, doughy skin texture		Procollagen-N-proteinase	ADAMTS-2
	Sagging, redundant skin	Premature rupture of membranes
	Excessive bruising	Large herniae

^a IP inheritance pattern

AD Autosomal Dominant, AR Autosomal Recessive