A 32-year-old Indian male presents with a laceration to his forearm sustained 6 weeks ago. On examination, the wound has healed but the scar is notably widened, atrophic, and has a characteristic "cigarette paper" appearance. His medical history reveals hypermobile joints and hyperextensible skin. The phase of wound healing marked **C** in the diagram involves replacement of weaker collagen with stronger collagen. Which of the following best explains the poor scar quality in this patient?

Explanation

## Why Defective type I collagen assembly due to mutations in COL5A1/COL5A2 (Classical Ehlers-Danlos Syndrome) is right During the remodeling phase marked **C** (3 weeks–1 year), type III collagen is progressively replaced by stronger type I collagen through the coordinated action of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs). In Classical Ehlers-Danlos Syndrome, mutations in COL5A1 or COL5A2 genes disrupt the assembly and cross-linking of type I collagen, preventing proper collagen maturation during remodeling. This results in persistently weak, disorganized collagen that cannot achieve normal tensile strength, manifesting as widened, atrophic "cigarette paper" or "fish-mouth" scars—exactly as described in this patient. The combination of hypermobile joints, hyperextensible skin, and poor wound healing is pathognomonic for Classical EDS. (Robbins 10e Ch 3) ## Why each distractor is wrong - **Type III collagen defect (COL3A1) causing vascular fragility and arterial rupture risk**: This describes Vascular (Type IV) Ehlers-Danlos Syndrome, which presents with arterial dissection, intestinal rupture, and uterine rupture in pregnancy—not the joint hypermobility and skin hyperextensibility seen in this patient. The scar phenotype is also different. - **Impaired hydroxylation of proline and lysine due to vitamin C deficiency (Scurvy)**: While scurvy does impair collagen cross-linking and cause poor wound healing, it presents acutely with bleeding gums, perifollicular hemorrhages, and anemia—not the chronic joint hypermobility and skin hyperextensibility characteristic of this patient's presentation. - **Excessive matrix metalloproteinase (MMP) activity overwhelming tissue inhibitor (TIMP) function**: Although MMPs are essential during remodeling phase **C** to degrade type III collagen, dysregulation of MMP/TIMP balance is not the primary defect in Ehlers-Danlos Syndrome. The fundamental problem is defective collagen synthesis and assembly, not excessive degradation. **High-Yield:** Classical Ehlers-Danlos (COL5A1/COL5A2 mutations) = hypermobile joints + hyperextensible skin + poor wound healing with widened atrophic scars; Vascular EDS (COL3A1) = arterial/visceral rupture risk; Scurvy = acute bleeding + poor healing without joint hypermobility. [cite: Robbins 10e Ch 3]