• Clinical science

Ehlers-Danlos syndrome and Marfan syndrome


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.


Marfan syndrome

MarFan syndrome is caused by a gene mutation in FBN1 on chromosome 15 (Fifteen), resulting in defective Fibrillin protein.

Ehlers-Danlos syndrome

  • 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


Clinical features

Marfan syndrome


The classic presentation of MFS includes aortic aneurysm or dissection, long extremities, arachnodactyly, joint hypermobility, and subluxation of the lens of the eye.

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)!

Ehlers-Danlos syndrome

  • Joint hypermobility with tendency to dislocate
  • Skeletal abnormalitis (e.g., scoliosis)
  • Tendency to bruise easily
  • Skin hyperextensibility
  • Frequent skin lacerations and poor skin healing (e.g., following surgery)
  • Hernias
  • Features of organ rupture (e.g., shock, local pain), especially in vascular EDS

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 diagnoses

Differential diagnosis of a marfanoid body habitus
Marfan syndrome Homocystinuria Multiple endocrine neoplasia 2B (MEN 2B)
Shared features
Characteristic features


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: Preliminary data suggest that ARBs (e.g., losartan) may have a protective or even reversing effect in some of the clinical manifestations of MFS.
    • Ehlers-Danlos syndrome: High-contact sports should be avoided and surgical procedures should be performed with caution.



  • 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.