• Clinical science

Ehlers-Danlos syndrome and Marfan syndrome


Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that affects the microfibrils and elastin in connective tissue throughout the body. MFS is associated with disorders of 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 connective tissue disorders with variable inheritance (including hypermobility EDS and vascular EDS), characterized by defective collagen synthesis and processing. Symptoms include varying degrees of hyperextensive skin, joint hypermobility, and tissue fragility (including that of vasculature).

The diagnosis of MFS and EDS is based on clinical criteria. Genetic testing can be used additionally to confirm or rule out the diagnosis of certain subtypes. Since there is currently no causal treatment for MFS or EDS, management typically involves an approach focusing on clinical features, including regular monitoring of complications (e.g., imaging of aortic aneurysm) and preventive care (e.g., antihypertensives to prevent aneurysm progression).

Etiology and classification

Marfan syndrome [1][2]

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

Ehlers-Danlos syndrome [1]

  • Defects in collagen are caused by mutations in certain genes (e.g., COL5A1, COL3A1) that control the synthesis and processing of different types of collagen (e.g., a defect in lysine-hydroxylysine cross-linking of tropocollagen leads to unstable collagen fibrils)
  • Inheritance patterns, severity, and type of collagen affected vary (can be autosomal dominant or recessive)
  • EDS is subclassified into 13 different types, based on clinical presentation, genetic defect, and type of collagen affected (e.g., hypermobility type, classical type). Only the most common types will be discussed here.
Types of Ehlers-Danlos syndrome
Name Genetic defect Affected protein Clinical presentation
Hypermobility (most common)
  • Unknown
  • Unknown
  • Joint instability (e.g., shoulder and patella dislocations) predominates
  • COL5A1
  • COL5A2
  • TNXB
  • Tenascin X
  • Milder than classical type (e.g., joint hypermobility with fewer dislocations)
  • COL3A1

Clinical features

Marfan syndrome [1][3][4]



  • Tall stature and long extremities
  • Joint hypermobility
    • Positive thumb sign: Patients are asked to place their thumbs in the palms of the same hand and then clench to form a fist. A positive thumb sign is present when the thumb protrudes beyond the ulnar border of the hand.
    • Positive wrist sign: Patients are asked to clasp the wrist of the opposite hand. A positive wrist sign is present when the little finger and thumb overlap.
  • High-arched palate
  • Arachnodactyly (achromachia); : abnormally long, slender fingers and toes
  • Pectus deformity
  • Pes planus (flat foot) or hindfoot valgus
  • Spinal deformities (scoliosis, hyperkyphosis)
  • Vertical overdevelopment of the head (dolichocephaly)
  • Winged scapula
  • Habitual dislocations (particularly the patella and shoulder)
  • Acetabular protrusion





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

Ehlers-Danlos syndrome [5]

The clinical features discussed here are seen in all types of EDS, but their severity may vary and certain symptoms predominate depending on the specific type.



  • Joint hypermobility with a tendency towards dislocation
  • Skeletal abnormalities (e.g., scoliosis, pectus deformity)


  • Tendency to bruise easily
  • Skin hyperextensibility
  • Frequent skin lacerations (e.g., with minor scratches)
  • Poor skin healing (e.g., following surgery )
  • Atrophic scars



  • Hernias
  • Organ rupture (e.g., gravid uterus)end causing pain and (potentially life-threatening) internal bleeding, especially seen with vascular EDS
  • Cervical insufficiency, uterine prolapse
  • Dental abnormalities: hypodontia, delayed eruption, molluscoid pseudotumors

The classic presentation of EDS involves hyperextensible skin, joint hypermobility, and a tendency to bleed easily.



Differential diagnoses

Differential diagnosis of a marfanoid body habitus
Inheritance pattern Skeletal Dermal Vascular Other
Marfan syndrome
  • Hyperextensive skin
  • Striae
Ehlers-Danlos syndrome
  • Fair complexion
Loeys-Dietz syndrome [9]
  • Congenital heart defects (e.g., ASD)
Multiple endocrine neoplasia 2B (MEN 2B)
  • Unaffected
Congenital contractural arachnodactyly (Beals syndrome) [10][11]
  • Unaffected
  • Intestinal atresia, malrotation

Marfan syndrome classically manifests with a superior and temporal displacement of the lens (upward and outward). Homocystinuria also results in a Marfanoid habitus, but manifests with inferior and medial displacement of the lens (downward and inward).

The differential diagnoses listed here are not exhaustive.


Applicable to MFS and EDS

  • No causal treatment
  • Interdisciplinary treatment of specific symptoms and manifestations, including:
  • Regular orthopedic, ophthalmological, and cardiological check-ups

Specific treatment [12]


Marfan syndrome [13][1]

  • Normal life expectancy: if diagnosed early and complications are managed appropriately
  • Cardiovascular complications: Disease progression should be carefully monitored and managed accordingly to prevent cardiovascular complications (e.g., aortic dissection).
  • Aortic root disease (e.g., aneurysm, dissection) is the most common cause of death.

Ehlers-Danlos syndrome [7][14][15]

  • Normal life expectancy in all types of EDS except vascular type
  • Life expectancy in vascular type: approx. 50 years