Random Dermatology MCQ - Ehlers-Danlos syndrome (EDS)

A 15-year-old girl presents with hypermobile joints, atrophic scars over her knees and elbows, and soft, velvety, hyperextensible skin. She has a history of easy bruising. Her father has similar features. Which of the following is the most common type of Ehlers-Danlos syndrome (EDS) and the underlying collagen defect?

A) Hypermobile EDS; unknown, but often linked to Tenascin-X
B) Classical EDS; type V collagen (COL5A1, COL5A2)
C) Vascular EDS; type III collagen (COL3A1)
D) Kyphoscoliotic EDS; lysyl hydroxylase deficiency
E) Dermatosparaxis EDS; procollagen I N-terminal peptidase deficiency

Correct Answer: B) Classical EDS; type V collagen (COL5A1, COL5A2)

Explanation

This presentation is classic for Classical Ehlers-Danlos Syndrome (cEDS), one of the major subtypes of EDS. The 2017 international classification defines 13 subtypes, with the classical type being one of the most common.

Key Clinical Features of Classical EDS (cEDS):

• Cutaneous:

  • Skin hyperextensibility: The skin is soft, velvety, and can be stretched excessively, but it recoils back after release.

  • Atrophic scarring: Wide, papyraceous (cigarette-paper-like) scars over bony prominences (knees, elbows, shins).

  • Easy bruising.

• Musculoskeletal:

  • Joint hypermobility (generalized).

• Other: Molluscoid pseudotumors (fleshy lesions over pressure points), spheroids (subcutaneous nodules on forearms/shins).

Genetic Defect and Pathophysiology:

• Most Common Genetics for cEDS: Mutations in the genes for type V collagen, COL5A1 and COL5A2. A small number of cases are caused by COL1A1 mutations.

• Mechanism: Type V collagen is a fibrillar collagen that regulates the assembly and diameter of the larger type I collagen fibrils. Defective type V collagen leads to abnormal collagen fibrillogenesis, resulting in the fragility of skin, joints, and other tissues.

Why Not the Other Options?

• (A) Hypermobile EDS (hEDS): This is now considered the most prevalent type overall. However, its genetic basis is largely unknown (though some families show Tenascin-X deficiency). It is a clinical diagnosis characterized by generalized joint hypermobility and associated musculoskeletal pain, with less pronounced skin involvement than the classical type. The dramatic skin features in this case (hyperextensibility, atrophic scarring) point more strongly to cEDS.

• (C) Vascular EDS (vEDS): Caused by type III collagen (COL3A1) defects. It is the most severe type due to the risk of arterial, uterine, or intestinal rupture. The skin is often thin and translucent with visible veins, but not typically as hyperextensible as in cEDS.

• (D) Kyphoscoliotic EDS (kEDS): Caused by a deficiency of lysyl hydroxylase (PLOD1 gene), leading to defective collagen cross-linking. It presents with severe muscle hypotonia at birth, kyphoscoliosis, and joint hypermobility.

• (E) Dermatosparaxis EDS (dEDS): Caused by a deficiency of procollagen I N-terminal peptidase. It features extremely fragile, sagging, and redundant skin.

Management:

• Supportive care: Physical therapy for joint stability, protective padding for fragile skin, genetic counseling.

• Avoid: Invasive procedures when possible due to poor wound healing.

Prognosis:
For cEDS, life expectancy is normal, but morbidity from joint instability and chronic pain is significant.

Note: While hEDS is the most common type by population prevalence, the classical type (cEDS) has the most well-defined genetic basis among the common forms and is characterized by the hallmark triad of skin hyperextensibility, atrophic scarring, and joint hypermobility. The autosomal dominant family history is also typical. It is critical to distinguish cEDS from the more life-threatening vascular type.