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Marfan Syndrome

Cataract & Refractive SurgeryTriadHigh YieldAlso: Marfan's Syndrome

Key Points

  • •Lens subluxation in Marfan is superotemporal — the opposite direction from homocystinuria (inferonasal). This is a classic exam question.
  • •Aortic root dilation is the most life-threatening feature; beta-blockers or ARBs are the cornerstone of medical management.
  • •Revised Ghent criteria (2010): ectopia lentis + aortic root Z-score >= 2 is sufficient for diagnosis without any other features.
  • •FBN1 mutations cause disease through both structural microfibril deficiency and dysregulated TGF-beta signaling.

Hallmark Features(Triad)

1

Superotemporal lens subluxation (ectopia lentis)

2

Skeletal abnormalities (tall stature, arachnodactyly)

3

Cardiovascular (aortic root dilation, MVP)

Finder Clues

Superotemporal lens subluxationTall stature with long limbsArachnodactylyAortic root dilationHigh myopiaRetinal detachmentMitral valve prolapseJoint hypermobilityFlat corneaPectus excavatum/carinatum
1. Definition

Autosomal dominant connective tissue disorder caused by FBN1 mutations, characterized by ocular, skeletal, and cardiovascular manifestations.

2. Genetics

Autosomal dominant. FBN1 gene on chromosome 15q21 encoding fibrillin-1. ~25% de novo mutations.

3. Pathogenesis

Molecular basis:

  • Fibrillin-1 is a major structural glycoprotein of extracellular microfibrils
  • Mutations in FBN1 lead to defective microfibril assembly
  • Results in weakened connective tissue and dysregulated TGF-beta signaling

Organ-specific effects:

  • Zonules — zonular weakness causes progressive lens subluxation, typically superotemporal (zonules break inferonasally, lens shifts superotemporally)
  • Aorta — medial degeneration leads to progressive root dilation and risk of dissection
  • Skeleton — excessive long-bone growth mediated through dysregulated TGF-beta activity
4. Clinical Features

Diagnostic framework:

  • Revised Ghent criteria (2010) emphasize aortic root dilation and ectopia lentis as cardinal features

Skeletal features:

  • Tall stature — arm span > height
  • Arachnodactyly — positive Steinberg thumb sign and Walker-Murdoch wrist sign
  • Pectus excavatum or carinatum
  • Scoliosis, pes planus, protrusio acetabuli
  • Reduced upper-to-lower segment ratio
  • Increased arm span-to-height ratio

Other features:

  • Striae distensae on skin
  • Spontaneous pneumothorax
  • Dural ectasia
5. Ocular Manifestations

Lens:

  • Ectopia lentis — occurs in ~60-80% of patients (most commonly cited as ~75%)
  • Direction: superotemporal (classic exam point)
  • Usually bilateral and progressive
  • Lens equator may be visible in the undilated pupil

Anterior segment:

  • High myopia — from increased axial length and lens-induced
  • Flat cornea — reduced corneal curvature
  • Hypoplastic iris dilator — miotic pupil
  • Angle abnormalities may predispose to glaucoma

Posterior segment:

  • Increased axial length
  • Increased risk of retinal detachment — especially after lens surgery
6. Systemic Manifestations

Cardiovascular (most dangerous):

  • Aortic root dilation — most life-threatening feature
  • Aortic dissection — leading cause of death
  • Mitral valve prolapse with regurgitation
  • Tricuspid valve prolapse

Skeletal:

  • Disproportionate tall stature
  • Arachnodactyly, scoliosis
  • Pectus deformities
  • Joint hypermobility, pes planus

Pulmonary:

  • Apical blebs and spontaneous pneumothorax

Integumentary:

  • Striae, hernias

Neurological:

  • Dural ectasia (lumbosacral)
7. Diagnosis

Revised Ghent nosology (2010):

Simplified diagnostic pathways:

  • Aortic root dilation (Z-score >= 2) AND ectopia lentis = Marfan diagnosis regardless of other findings
  • Without ectopia lentis: aortic root dilation + FBN1 mutation or systemic score >= 7

Systemic scoring (maximum 20 points; >=7 = systemic involvement):

  • Wrist AND thumb signs — 3 points
  • Wrist OR thumb sign — 1 point
  • Pectus carinatum — 2 points
  • Pectus excavatum or chest asymmetry — 1 point
  • Hindfoot deformity — 2 points
  • Plain pes planus — 1 point
  • Pneumothorax — 2 points
  • Dural ectasia — 2 points
  • Protrusio acetabuli — 2 points
  • Reduced US/LS AND increased arm span/height AND no severe scoliosis — 1 point
  • Scoliosis/kyphosis — 1 point
  • Reduced elbow extension — 1 point
  • Facial features — 1 point
  • Skin striae — 1 point
  • Myopia > 3D — 1 point
  • MVP — 1 point

Genetic testing for FBN1 mutations confirms but is not required for clinical diagnosis.

8. Differential Diagnosis

Key differentials:

  • Homocystinuria — inferonasal subluxation, intellectual disability, thromboembolic events, autosomal recessive
  • Loeys-Dietz syndrome — aggressive aortic disease, bifid uvula, hypertelorism, no ectopia lentis
  • Ehlers-Danlos vascular type — arterial rupture, translucent skin
  • Weill-Marchesani syndrome — short stature, brachydactyly, microspherophakia with inferior subluxation (may dislocate anteriorly causing pupillary block glaucoma)
  • Ectopia lentis et pupillae
  • Isolated familial ectopia lentis
9. Management

Cardiovascular:

  • Beta-blockers (atenolol) or ARBs (losartan) to reduce aortic wall stress and slow root dilation
  • Prophylactic aortic root replacement when diameter reaches 5 cm (or 4.5 cm with family history of dissection)
  • Regular echocardiographic surveillance

Ocular:

  • Spectacle correction for myopia and astigmatism
  • Contact lenses may be considered
  • Lens extraction (typically lensectomy/vitrectomy) when subluxation causes significant visual axis obstruction or refractory amblyopia
  • IOL options:
  • Scleral-fixated
  • Iris-fixated
  • Capsular tension ring with in-the-bag placement (if adequate capsular support)
  • Monitor for retinal detachment

Skeletal:

  • Orthopedic management of scoliosis and chest wall deformities

Genetics:

  • Genetic counseling for family planning (50% transmission risk)
10. Prognosis

Life expectancy:

  • Improved dramatically with modern cardiovascular management — from ~45 years to near-normal lifespan
  • Aortic dissection remains the leading cause of mortality

Ocular prognosis:

  • Generally good with appropriate refractive correction and timely surgical intervention for lens subluxation

Regular multidisciplinary follow-up (cardiology, ophthalmology, orthopedics, genetics) is essential.

Clinical Pearls

1

The Steinberg thumb sign (entire distal phalanx of the adducted thumb extends beyond the ulnar border of the clenched fist) and Walker-Murdoch wrist sign (thumb and little finger overlap when grasping contralateral wrist) are quick bedside tests for arachnodactyly.

2

Before any lens surgery in Marfan, obtain echocardiography — general anesthesia in patients with aortic root dilation carries significant hemodynamic risk.

3

Flat cornea (mean K < 43 D) in Marfan can confound IOL power calculations; consider adjusting for the reduced corneal power.

Mnemonics

Marfan vs Homocystinuria Lens Direction

Marfan = Up and Out (superotemporal)

Homocystinuria = Down and In (inferonasal)

Key differentiating feature between the two causes of ectopia lentis

Marfan Triad

L—Lens subluxation (superotemporal)

A—Aorta (root dilation)

S—Skeleton (tall, arachnodactyly)

Three organ system involvement in Marfan syndrome

References

  1. textbookKanski's Clinical Ophthalmology: A Systematic Approach— Elsevier (2020)
  2. paperRevised Ghent Nosology for the Marfan Syndrome— Journal of Medical Genetics (2010)
  3. paperManagement Strategies of Ocular Abnormalities in Patients with Marfan Syndrome: Current Perspective— Journal of Ophthalmic and Vision Research (2019)
  4. textbookParsons' Diseases of the Eye— Elsevier (2019)
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