Marfan syndrome

Marfan syndrome is a multi system hereditary connective tissue disease with a high penetrance and variable expression.

Epidemiology

It is inherited in an autosomal dominant fashion in a majority of cases, although up to a 1/3^rd of cases result from spontaneous mutations. The disease has a high penetrance with variable expression. The estimated prevalence ranges around 2 - 6 per 100000 ^2,5. There is no recognised gender predilection.

Diagnostic criteria

The Ghent nosology was established in 1995 for clinical diagnosis of the disease ⁷. Individuals require either two major and one minor feature or one major and four minor feature for diagnosis

Pathology

Results from a defect in fibrillin 1 (FBN1) gene located in chromosome 15 which is responsible for cross linking collagen 

Disease spectrum and associated features

Skeletal

• general
  • tall stature
  • osteopaenia ¹
  • joint laxity
    • recurrent dislocations
• spine / skull
  • high arched palate
  • atlanto-axial subluxation
  • dural ectasia
  • increased interpedicular distance
  • kyphoscoliosis
  • enlarged sacral foramina
  • meningocoeles 
    • pre sacral meningocoele
    • lateral sacral meningocoele
  • vertebral scalloping
• pelvis / lower limbs
  • progressive protrusio acetabuli
  • slipped upper femoral epiphyses (SUFE)
  • tibial subuxation ⁵
  • patella alta
  • pes planus
  • hallux valgus
  • clubfoot
• hands
  • arachnodactyly
  • protrustion of thumb beyond fist when clenched (Steinberg sign)
  • flextion deformity of 5^th finger
• chest wall deformities (present in up to 2/3^rds of cases ²)
  • pectus excavatum
  • pectus carinatum

Cardiovascular

Cardiovascular complications tend to be most frequent cause of death ².

• arterial dissection
• aortic aneurysm
• aortic valve regurgitation (AR)
• aortic coarctation
• aortic sinus dilatation
• myxomatous degeneration of the mitral valve
• pulmonary arterial dilatation

Ocular

• ectopia lentis : lens usually displaced upwards and out
• myopia
• retinal detachment
• megalocornea

Chest

• spontaneous pneumothorax
• lung cysts and bullae formation

Radiographic features

Please refer to individual articles for respective features

Etymology

First described in 1896 by Antoine Bernard-Jean Marfan : French pediatrician (1858 - 1942) 

Differential diagnosis

• patients with Loeys-Dietz syndrome have similar feautures to Marfan syndrome
• patients with homocystinuria may resemble those with Marfan syndrome in some aspects ⁸
• patients with multiple endocrine neoplasia type IIb may have a Marfan syndrome like body habitus 
• patients with the Beals syndrome have some features of Marfan syndrome