Ehlers-Danlos Syndromes (EDS) are inherited disorders affecting connective tissue throughout the body. This tissue, primarily composed of collagen, provides structure and support to skin, joints, blood vessels, and organs. Genetic mutations compromise collagen production or processing, resulting in tissue that is fragile and overly flexible. This article clarifies the historical classification of Ehlers-Danlos Syndrome Type II (ED II) and its current understanding.
Understanding the Historical Classification of ED II
The classification system for Ehlers-Danlos Syndromes has undergone several revisions, leading to confusing nomenclature. The original system used Roman numerals (Type I, Type II, etc.), grouping both Type I and Type II under what is now called the Classical Type of EDS.
Historically, ED II described individuals with the Classical Type who presented with milder symptoms, specifically less severe skin fragility and joint hypermobility than those classified as ED Type I. The 1997 Villefranche nosology consolidated both Type I and Type II into the single category of “Classical EDS.”
The 2017 international classification abolished the Roman numeral system, favoring criteria emphasizing genetic and clinical features. Therefore, ED II is now known as Classical Ehlers-Danlos Syndrome (cEDS). This reclassification recognized that these clinically related conditions share the same underlying genetic causes and core features.
Primary Physical Manifestations
The physical presentation of cEDS is characterized by connective tissue abnormalities affecting the skin and joints. The skin is typically soft and smooth, often described as having a velvety texture due to faulty collagen structure. This results in significant skin hyperextensibility; the skin stretches far beyond normal and snaps back quickly.
A defining feature is abnormal wound healing, which results in characteristic atrophic scars. These scars are wide, thin, and often depressed, sometimes described as resembling “cigarette paper,” particularly over pressure points. Easy bruising disproportionate to the trauma sustained is also common.
Generalized joint hypermobility is a core component, though less extreme than in the Hypermobile Type of EDS. Joint laxity often leads to recurring instability, including frequent subluxations and full dislocations. Less common findings include subcutaneous spheroids (small, hard, mobile lumps) and molluscoid pseudotumors (calcified hematomas over pressure points).
Genetic Basis and Inheritance
Classical Ehlers-Danlos Syndrome (cEDS) is primarily caused by mutations in the genes COL5A1 and COL5A2. These genes provide instructions for making the alpha chains of Type V collagen, which regulates the formation and diameter of collagen fibrils. The resulting defect impairs connective tissue integrity.
In a smaller number of cases, cEDS has been linked to mutations in the COL1A1 gene. The most common genetic mechanism involves haploinsufficiency of COL5A1, where a mutation causes one copy of the gene to produce no functional protein, reducing the total amount of Type V collagen by half.
cEDS follows an Autosomal Dominant inheritance pattern. This means a person only needs to inherit one copy of the altered gene from one parent. Each child of an affected parent has a 50% chance of inheriting the pathogenic variant. The condition can also arise spontaneously from a new (de novo) mutation.
Diagnosis and Management Approaches
Diagnosis of cEDS begins with a clinical evaluation based on the 2017 diagnostic criteria. Providers look for major criteria (skin hyperextensibility and atrophic scarring) combined with generalized joint hypermobility or minor criteria (e.g., easy bruising and family history). Definitive diagnosis is confirmed through molecular genetic testing.
Genetic testing involves sequencing the COL5A1 and COL5A2 genes to identify the causative mutation. Management of cEDS is supportive, focusing on preventing complications and treating symptoms, as there is no cure for the underlying collagen defect.
Non-surgical interventions are the mainstay of care, centered on protecting fragile tissues and improving joint stability. Physical therapy is recommended to strengthen muscles surrounding unstable joints, compensating for ligamentous laxity. Pain management may include non-steroidal anti-inflammatory drugs (NSAIDs) or topical agents. Careful wound closure techniques are necessary to ensure surgical wounds heal with minimal widening.