Table 2.

Clinical Diagnosis of Hypermobile EDS.

The Clinical Diagnosis of hEDS Requires the Simultaneous Presence of 3 Criteria (1, 2 and 3)
Criterion 1	Generalized joint hypermobility (GJH), defined by Beighton Score (BS). GJH is diagnosed with ➣BS ≥ 6 for pre-pubertal children and adolescents ➣BS ≥ 5 for pubertal men and women up to the age of 50 ➣BS ≥ 4 for those >50 years of age
Criterion 2 (Two or more among the features A–C must be present)	SIGN A (five or more of the following manifestations should be present): Unusually soft or velvety skin Mild skin hyperextensibility 1 Unexplained striae 2 Bilateral piezogenic papules of the heel 3 Recurrent or multiple abdominal hernia(s), such as umbilical, inguinal or crural Atrophic scarring involving at least two sites and without the formation of truly papyraceous and/or hemosiderotic scars 4 Pelvic floor, rectal, and/or uterine prolapse in children, men or nulliparous women Dental crowding and high or narrow palate 5 Arachnodactyly 6 Arm span-to-height ≥ 1.05 Mitral valve prolapse mild or greater based on strict echocardiographic criteria Aortic root dilatation with Z-score > +2 SIGN B: Positive family history, with one or more first degree relatives independently meeting the diagnostic criteria for hEDS SIGN C (at least one): Musculoskeletal pain in two or more limbs, recurring daily for at least 3 months Chronic, widespread pain for ≥3 months Recurrent joint dislocations or frank joint instability, in the absence of trauma
Criterion 3 (All must be met)	1. Absence of unusual skin fragility, which should prompt consideration of other types of EDS 2. Exclusion of other heritable and acquired connective tissue disorders (HCTDs) (based on history, physical exam, and/or molecular genetic testing), including autoimmune and rheumatologic conditions 3. Exclusion of alternative diagnoses that include joint hypermobility by means of hypotonia and/or connective tissue laxity

¹ Mild skin hyperextensibility, assessed at a site lacking excess or loose skin and without evidence of prior trauma by gently pulling until resistance is met. An ideal location is the volar surface of the non-dominant forearm, where the upper limit of normal extensibility is 1.5 cm [5]. Extensor surfaces of joints have excess skin and should not be used. More significant extensibility (e.g., >2.0 cm) should prompt consideration of other EDS types, especially in combination with other cutaneous features, such as papyraceous scars, molluscoid pseudotumors and/or subcutaneous spheroids. ² Unexplained (because there is not a history of significant gain or loss of body weight) striae distensae or rubrae at the back, groins, thighs, breast, and/or abdomen in adolescents, men, or prepubertal females ³ Bilateral piezogenic papules (herniations of subcutaneous heel fat visible upon standing) of the heel; these must be present bilaterally to be considered positive. These are rarely found in children but can be easily found in adults with history of prolonged standing (occupational) [22], marathon runners or weightlifters. ⁴ Atrophic scarring involving at least two sites and without the formation of papyraceous and/or hemosideric scars. Atrophic scarring is defined as scars from linear traumatic lacerations or single surgery that are unusually shallow and/or wider than the original wound. Atrophic scars deriving from multiple skin incision, wound infection or inflammatory conditions are to be considered negative ⁵ Dental crowding (including a history of crowding corrected by orthodontia) and high or narrow palate. Both conditions must be positive to count toward this feature. ⁶ Arachnodactyly, defined as either bilateral positive wrist sign (Steinberg sign) or bilateral positive thumb sign (Walker sign).