- Clinical science
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder affecting the microfibrils and elastin in connective tissue throughout the body. MFS is associated with pathological manifestations in the cardiovascular system (e.g., mitral valve prolapse, aortic aneurysm, and dissection), the musculoskeletal system (e.g., tall stature with disproportionately long extremities, joint hypermobility), and the eyes (e.g., subluxation of the lens of the eye).
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of six connective tissue disorders with variable inheritance in which the synthesis and processing of collagen are defective. Patients present with varying degrees of hyperelastic skin, joint hypermobility, and tissue fragility (including that of vasculature).
The diagnosis of MFS and EDS is based on clinical criteria, and genetic testing can be used additionally under certain circumstances. There is currently no causal treatment for MFS or EDS; a symptom-based approach is generally necessary. Primary prevention includes genetic counseling, while tertiary prevention involves regular monitoring for complications.
- Mutation of fibrillin-1 gene (FBN1) on chromosome 15 → defective connective tissue microfibrils → defective elastin
- Autosomal dominant inheritance pattern with variable penetrance
- Various mutations in genes that control the synthesis and processing of collagen (e.g., defect in lysine-hydroxylysine cross-linking of tropocollagen → unstable collagen fibrils)
EDS type (Villefranche classification): Inheritance patterns and type of collagen affected vary (can be autosomal dominant or recessive)
- Mutation of type V collagen (e.g., COL5A1, COL5A2) → classic EDS (types I and II) in which joint and skin manifestations predominate
- Hypermobility EDS (type III) (most common type): joint manifestations predominate
- Mutation of type III procollagen (e.g., COL3A1) → vascular EDS (type IV) in which cardiovascular manifestations predominate
Marfan syndrome classically results in a superior and temporal displacement of the lens (upward and outward). Homocystinuria also results in a Marfanoid habitus but presents with inferior and medial displacement of the lens (downward and inward)!
The classic presentation of EDS involves hyperextensible skin, joint hypermobility, and a tendency to bleed easily.
- Both are typically clinical diagnoses; can be confirmed with genetic testing
- Tests to identify specific manifestations
|Differential diagnosis of a marfanoid body habitus|
|Marfan syndrome||Multiple endocrine neoplasia 2B ( )|
The differential diagnoses listed here are not exhaustive.
- No causal treatment
- Interdisciplinary treatment of specific symptoms and manifestations (e.g., aortic dilatation treated with beta-blockers and, if the necessity arises, surgery; scoliosis treated with bracing and, if the necessity arises, surgery; physical therapy, analgesia for pain)
- Regular orthopedic, ophthalmological, and cardiological check-ups
- Specific therapy
Marfan syndrome: patients can expect a normal lifespan, if the disorder is diagnosed early and complications are managed appropriately
- Aortic root disease is the most common cause of mortality
- Ehlers-Danlos syndrome: Life expectancy is typically normal with the exception of vascular EDS, which has a reduced life expectancy of ∼ 50 years.