Table 6 Primary connective tissue diseases

Ehlers-Danlos syndrome

COL1A1;

COL1A2;

COL3A1, COL5A1;

COL5A2;

TNXB, and others

AD and AR

Skin hyperextensibility with atrophic scarring, generalized joint hypermobility, exercise intolerance, muscle weakness, arterial rupture at young age, spontaneous sigmoid colon, or uterine rupture; MCAS and POTS may be associated

Molecular analysis^#; Increased serum tryptase or urinary N-MH, PG metabolites, LTE4, ≥ 20 MCs per HPF in extracutaneous tissue biopsy in case of MCAS

Angiotensin receptor blocker and/or beta-blocker for aneurysm, pain relief drugs, physiotherapy, and rehabilitation therapy; Surgical intervention (aneurysm, dissection, organ rupture); Antihistamines, leukotriene antagonists, 5-lipoxygenese inhibitors, and PG blockers in case of MCAS

Marfan syndrome

FBN1

AD

Wrist and thumb sign, arachnodactyly, generalized joint hypermobility, anterior chest deformity (pectus excavatum and/or carinatum), pneumothorax, myopia, ectopia lentis, aortic root dilatation

Molecular analysis^#. Aortic dilation (Z-score ≥ 2 SD) on echocardiography

Angiotensin receptor blocker and/or b-blocker for aneurysm, pain relief drugs, physiotherapy, and rehabilitation therapy; Surgical intervention (aneurysm, dissection)

Loeys-Dietz syndrome

TGFBR1;

TGFBR2;

TGFB2;

TGFB3;

SMAD3;

SMAD2.

AD

Generalized joint hypermobility, chest deformity, scoliosis, bifid (split or forked) uvula, cleft palate, hypertelorism; Aortic root aneurysms, arterial tortuosity, dissections, mitral valve prolapse

Molecular analysis^#

Angiotensin receptor blocker and/or b-blocker for aneurysm, pain relief drugs, physiotherapy, and rehabilitation therapy; Surgical intervention (aneurysm, dissection)