What subtype of Ehlers-Danlos syndrome (EDS) is associated with genetic markers for Collagen Type I Alpha 1 (COL1A1) and Tenascin XB (TNXB)?

From the Guidelines

A patient with genetic markers for COL1A1 and TNXB is likely to have a subtype of Ehlers-Danlos syndrome (EDS) that presents with features of Classical-like EDS, given the association of these genes with this subtype 1. The genetic markers for COL1A1 and TNXB suggest a complex presentation of EDS, with COL1A1 mutations linked to Classical-like EDS or Arthrochalasia EDS, and TNXB mutations characteristic of Classical-like EDS type 2. Key aspects of this subtype include:

• Joint hypermobility
• Skin fragility
• Potential cardiovascular complications Management of this subtype typically involves:
• Multidisciplinary care
• Physical therapy to strengthen muscles around hypermobile joints
• Skin care to prevent injuries
• Pain management
• Regular cardiovascular monitoring
• Genetic counseling to understand inheritance patterns and implications for family planning, as EDS subtypes have different inheritance patterns, with many following autosomal dominant transmission 1. It is essential to prioritize the patient's quality of life, morbidity, and mortality when developing a treatment plan, considering the potential complications associated with this subtype of EDS.

From the Research

Ehlers-Danlos Syndrome Subtype

The subtype of Ehlers-Danlos syndrome (EDS) associated with genetic markers for Collagen Type I Alpha 1 (COL1A1) and Tenascin XB (TNXB) is:

• Classical-like Ehlers-Danlos syndrome (clEDS) due to biallelic null variants in TNXB 2, 3
• Classical Ehlers-Danlos syndrome (cEDS) with a propensity to arterial events due to a COL1A1 variant 4, 5
• It is worth noting that while COL1A1 is typically associated with cEDS, TNXB is associated with a classical-like phenotype that lacks atrophic scarring 2, 3

Genetic Markers

Key genetic markers associated with this subtype of EDS include:

• COL1A1 variants, such as p.(Arg312Cys) 4 and c.2050G > A; p.Glu684Lys 5
• TNXB variants, such as c.8278C > T p.(Gln2760*) and c.(2358 + 1_2359 - 1)_(2779 + 1_2780 - 1)del 2
• These genetic markers can help diagnose and distinguish between different subtypes of EDS 2, 4, 3, 5

Clinical Characteristics

Clinical characteristics of this subtype of EDS may include:

• Hyperextensible skin and generalized joint hypermobility 2, 4, 3, 5
• Vascular complications, such as arterial aneurysms and dissections 4
• Musculoskeletal complications, such as contractures and kyphoscoliosis 2, 5
• These clinical characteristics can vary widely between individuals and families 6