Dermatology MCQ - Genetic Disorders - Ehlers–Danlos Syndrome

A 20-year-old woman is referred for evaluation of joint hypermobility. She has a history of frequent ankle sprains and shoulder dislocations. On examination, you note her skin is soft, doughy, and easily hyperextensible. She has several wide, atrophic, "cigarette-paper" scars over her knees and shins from minor injuries. The Beighton score is 7/9. Her facial appearance is normal, and there is no translucency of the skin. Based on the 2017 International Classification, what is the most likely diagnosis and the primary pathophysiological defect?

A. Hypermobile Ehlers-Danlos syndrome (hEDS); molecular basis not yet fully defined.
B. Classical Ehlers-Danlos syndrome (cEDS); defect in type V collagen (COL5A1/COL5A2).
C. Vascular Ehlers-Danlos syndrome (vEDS); defect in type III collagen (COL3A1).
D. Kyphoscoliotic Ehlers-Danlos syndrome (kEDS); defect in lysyl hydroxylase 1 (PLOD1).
E. Arthrochalasia Ehlers-Danlos syndrome (aEDS); defect in type I collagen (COL1A1/COL1A2).

Correct Answer: B. Classical Ehlers-Danlos syndrome (cEDS); defect in type V collagen (COL5A1/COL5A2).

Answer and Explanation

The correct answer is B. This question clearly describes Classical EDS (cEDS). The diagnostic hallmarks are: 1) Skin hyperextensibility with a soft/doughy texture, 2) Characteristic atrophic ("cigarette-paper") scarring, and 3) Generalized joint hypermobility (high Beighton score). The absence of thin/translucent skin or abnormal facies argues against vEDS. cEDS is most commonly caused by autosomal dominant mutations in the genes encoding type V collagen (COL5A1, COL5A2).

Why the Other Options are Incorrect:

• A. Hypermobile EDS (hEDS): While joint hypermobility is present, hEDS does not feature the classic atrophic scarring or significant skin hyperextensibility described. It is a clinical diagnosis of exclusion when criteria for other types are not met.

• C. Vascular EDS (vEDS): vEDS is characterized by thin, translucent skin with visible veins, distinctive facial features (acrogeria), and a high risk of arterial/organ rupture. The skin is often not velvety, and scarring may be atrophic but the clinical context is dominated by vascular risk, not joint instability.

• D. Kyphoscoliotic EDS (kEDS): This presents with congenital muscle hypotonia, severe progressive scoliosis, and often ocular fragility. Skin may be hyperextensible but the clinical picture is distinct.

• E. Arthrochalasia EDS (aEDS): This is characterized by severe congenital hip dislocation and generalized joint hypermobility with recurrent subluxations. Skin is hyperextensible but scarring is not a prominent feature.

Additional High-Yield Information for Exams:

• 2017 International Classification: This system defines 13 subtypes. For cEDS, major criteria are skin hyperextensibility + atrophic scarring. Minor criteria include easy bruising, molluscoid pseudotumors, and joint hypermobility.

• Key Complications in cEDS vs. vEDS:

  • cEDS: Major morbidity from joint instability, chronic pain, dislocations, and poor wound healing. Life expectancy is typically normal.

  • vEDS: Major mortality from spontaneous arterial rupture (e.g., mesenteric, splenic), dissection (aortic), and hollow organ perforation (colon, uterus). Median life expectancy is ~50 years.

• Management Rationale:

  • For cEDS: Physical therapy for joint stabilization and muscle strengthening is cornerstone. Protective braces, pain management, and careful surgical technique for wound closure are key. Genetic counseling.

  • For vEDS: Prophylactic beta-blockers, avoidance of invasive procedures, vascular surveillance imaging, and urgent genetic counseling/testing for family members are critical.