Genetics · MU Sofia

24 – Hereditary Connective Tissue Diseases: Ehlers–Danlos Syndrome & Marfan Syndrome

Covers the two hereditary connective tissue disorders, starting with Ehlers–Danlos syndrome: its main gene defects by subtype, inheritance, the pathophysiology from collagen defects to tissue fragility, a table of clinical types, clinical features, diagnosis with the Beighton score, and management. It then moves to Marfan syndrome, covering FBN1 and fibrillin-1, the TGF-β pathway, a table of skeletal, ocular, cardiovascular and skin manifestations, the Ghent criteria, and drug and surgical treatment. A closing table compares the two conditions side by side.

Inside: 5 sections · 7 labelled pictures · 3 tables · 15 flashcards · 5 min

Topic 24 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 5 sections, about 501 words (5 min of reading), with 15 flashcards.

In this note

  1. 24 – Hereditary Connective Tissue Diseases: Ehlers–Danlos Syndrome & Marfan Syndrome
  2. Definition
  3. I. EHLERS–DANLOS SYNDROME (EDS)
  4. II. MARFAN SYNDROME (MFS)
  5. III. Comparison: Ehlers–Danlos vs Marfan Syndrome

Definition

Hereditary connective tissue diseases are genetic disorders affecting structural proteins like collagen, elastin, and fibrillin, which provide strength and elasticity to skin, ligaments, bones, and vessels.

I. EHLERS–DANLOS SYNDROME (EDS)

Ehlers–Danlos Syndrome represents a group of heritable connective tissue disorders characterized by hyperextensible skin, joint hypermobility, and tissue fragility (especially vessels and internal organs). Different subtypes result from mutations in collagen-encoding or modifying genes, leading to reduced collagen strength and elasticity.

Genetic and Molecular Basis

  • Main defective genes:
  • COL5A1, COL5A2 → Classical type (Type I/II EDS).
  • COL3A1 → Vascular type (Type IV EDS).
  • PLOD1 → Kyphoscoliotic type (Type VI).
  • ADAMTS2, TNXB, FKBP14 → Rare forms.
  • Type of inheritance:
  • Mostly autosomal dominant, some autosomal recessive forms.
  • Molecular defect:
  • Abnormal collagen structure or processing (hydroxylation/cross-linking failure).
  • Results in reduced tensile strength of connective tissue.

Pathophysiology

  1. 1. Mutations affect collagen synthesis, assembly, or cross-linking.
  2. 2. Collagen fibrils become thin, irregular, and poorly organized.
  3. 3. Reduced stability → stretchable and fragile tissues.
  4. 4. In blood vessels → arterial rupture risk.
  5. 5. In skin and joints → hyperextensibility and dislocations.
  6. 6. In severe subtypes → organ rupture (uterus, intestines).

Major Clinical Types

Clinical Features

  • Skin:
  • Thin, soft, hyperextensible, and easily bruised.
  • Poor wound healing → atrophic scars.
  • Joints:
  • Hypermobile with frequent subluxations or dislocations.
  • Chronic joint pain.
  • Vascular system:
  • Fragile vessels → spontaneous rupture (especially in vascular type).
  • Possible aneurysms or GI perforation.
  • Ocular:
  • Keratoconus, globe rupture, retinal detachment (kyphoscoliotic type).
  • Other:
  • Hernias, uterine rupture in pregnancy.

Diagnosis

  • Clinical examination (hypermobile joints, skin signs).
  • Beighton score for joint hypermobility.
  • Molecular testing for specific gene mutations.
  • Skin biopsy → abnormal collagen fibrils under electron microscopy.

Management

  • No curative therapy → symptomatic and preventive care.
  • Physiotherapy to strengthen muscles and protect joints.
  • Avoid trauma and invasive procedures.
  • Cardiovascular monitoring in vascular EDS.
  • Genetic counseling is essential for family planning.

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