Table 1:

Pathology and phenotypes of connective tissue disorders.

Pathology	Tissues Affected	Tissue Phenotype	Mechanism	Treatment
Marfan’s Syndrome [15–17, 19–21]	Limbs, digits, spine, heart, lungs, eyes, bone	Elongated limbs and digits, flexibility, scoliosis	Fibrillin-1	Beta blockers, surgery, avoid exercise
Ehler’s Danlos Syndrome [22–25]	Skin, aorta, spine, cartilage	Loose joints, stretchy tissues, abnormal scarring	Col1a1, col1a2, col3a1, col5a1, Tnxb	Physical therapy, pain relief, surgery
Osteogenesis Imperfecta [26]	Bone, eye, joints, heart, teeth, lung, ears	Brittle bones, blue tinge in eye, short height, loose joints, hearing loss, aortic dissection	Col 1–3	Bisphosphonates
Myxomatous Degeneration [27, 28]	Mitral valve	Displacement of thickened mitral valve leaflet into left atrium	Fibrosis and excess dermatan sulfate	Beta blockers, blood thinners, surgical replacement
Rheumatoid Arthritis [31–33]	Joints, skin, eyes, lungs, heart, vessels	Women (40–60yo); Inflamed, thickened synovium;	Immune system attacks synovium, mTORC1	NSAIDs, DMARDS, biologics, JAK inhibitors
Lupus [34–36]	Joints, skin, kidneys, blood, brain, heart, lungs	Women (15–45yo); flares, fatigue, fever, joint pain, swelling, rash, skin lesions, dry eyes, headaches	Autoimmune; Vitamin D HLA; IRF5, PTPN22, STAT4, CDKN1A, ITGAM, BLK, NFSF4, BANK1	NSAIDs, antimalarial drugs, corticosteroids, immunosuppresants, biologics
Scleroderma [34, 37–42]	Skin, vessels, muscle, internal organs	Women (mid age) Thickened skin, increased tissue stiffness, calcium deposits	HLA; collagen synthesis, T lymphocyte activation	Vitamin D
Osteoarthritis [65–70]	Cartilage	Reduced modulus, reduced GAG	Chronic overuse, aging, trauma, IL1β, TNF, Cox2, MMPs	Physical therapy, NSAID, corticosteroid, surgery
Tendinopathy [76–85]	Tendon	Reduced modulus, hypercellularity, fiber disorganization	Chronic overuse, aging, trauma, IL1β, IL4, IL-17, TNF	Physical therapy, NSAID, corticosteroid, surgery