Ehlers-Danlos syndrome and Marfan syndrome

Epidemiology

---

Etiology

Marfan syndrome

• Mutation of fibrillin-1 gene (FBN1) on chromosome 15 → defective fibrillin (a glycoprotein that forms a supportive sheath around elastin) → defective connective tissue microfibrils → defective elastin
• Autosomal dominant inheritance pattern with variable penetrance

Mnemonic

MarFan syndrome is caused by a gene mutation in FBN1 on chromosome 15 (Fifteen), resulting in defective Fibrillin protein.

Ehlers-Danlos syndrome

• Mutations in genes (e.g., COL5A1, COL3A1) that control the synthesis and processing of different types of collagen → collagen defects (e.g., a defect in lysine-hydroxylysine cross-linking of tropocollagen leads to unstable collagen fibrils)
  • Caused by a deficiency in procollagen peptidase, the enzyme that cleaves terminal propeptides from procollagen in the extracellular space. Impaired propeptide removal results in the formation of soluble collagen that does not properly crosslink.

    Drawing 2026-01-15 21.36.00.excalidraw

    ⚠ Switch to EXCALIDRAW VIEW in the MORE OPTIONS menu of this document. ⚠ You can decompress Drawing data with the command palette: ‘Decompress current Excalidraw file’. For more info check in plugin settings under ‘Saving’

    Excalidraw Data

    Text Elements

    Vitamin C Deficiency

    Osteogenesis Imperfecta

    Ehlers-Danlos

    Menkes Disease

    Embedded Files

    58c7f467e25b3598403f962e309bd81ecd1fe2c6: Pasted Image 20260115213631_102.png

    Link to original

---

Pathophysiology

---

Clinical features

Tip

The classic presentation of MFS includes aortic aneurysm or dissection, long extremities, arachnodactyly, joint hypermobility, and subluxation of the lens of the eye.

Marfan Syndrome vs Homocystinuria

Feature	Marfan Syndrome	Homocystinuria
Inheritance	Autosomal Dominant	Autosomal Recessive
Defect	Fibrillin-1	Cystathionine synthase
Lens Dislocation	Upward (“Marfan looks up”)	Downward (“Homocystinuria looks down”)
Intellect	Normal	Intellectual disability t
CV Risk	Aortic dissection/aneurysm	Thromboembolism t
Treatment	β-blockers, ARBs	Vitamin B6 (Pyridoxine)

Link to original

---

Diagnostics

Feature	Marfan Syndrome	Ehlers-Danlos Syndrome
Defective Protein	Fibrillin-1 (elastic fibers)	Collagen
Key Skeletal	Arachnodactyly (long fingers), tall stature	Joint hypermobility/dislocations, normal stature
Key Skin	Striae	Skin hyperextensibility, fragile skin
Major CV Risk	Aortic dissection	Arterial/organ rupture (vascular type)
Key Ocular	Upward lens dislocation	Blue sclera

Pathology

---

• Cystic medial degeneration: a degeneration (necrosis) of large blood vessels such as the aorta.
  • Seen in disorders that cause increased arterial wall stress (e.g., hypertension, coarctation of the aorta) as well as connective tissue disorders (especially MFS and EDS)
  • Can lead to aortic aneurysm and aortic dissection
  • Histopathology
    • Loss, thinning, disorganization, and fragmentation of elastic tissue in the media
    • Accumulation of mucoid extracellular matrix
    • Loss of smooth muscle nuclei

Treatment

---