๐งฌ Marfan Syndrome (MFS)
Authors: Jana Wei Qiao, MD; Karl T. Clebak, MD, MHA, FAAFP
๐งพ DESCRIPTION
- Inherited disorder of connective tissue
- Multi-system involvement: cardiovascular, musculoskeletal, ocular, pulmonary, integument, and dura
- Diagnostic framework: Ghent criteria (revised Ghent II)
๐ถ PEDIATRIC CONSIDERATIONS
- Early scoliosis surgery may help
- Pectus deformities may worsen with puberty
- Monitor closely during growth spurts
๐คฐ PREGNANCY CONSIDERATIONS
- High-risk pregnancy; cardiologist consultation mandatory
- Avoid spinal anesthesia (risk: dural ectasia)
- Aortic root >47 mm: consider prophylactic surgery pre-pregnancy
- Use ฮฒ-blockers to reduce risk of aortic dilation
๐ EPIDEMIOLOGY
- Incidence: 1 in 5,000โ10,000
- No sex or racial predilection
- Often diagnosed in adolescence or early adulthood
- ~25% of cases from de novo FBN1 mutation
- Advanced paternal age increases risk of new mutation
๐งฌ ETIOLOGY & GENETICS
- Mutation: FBN1 gene (chromosome 15)
- Inheritance: Autosomal Dominant, complete penetrance, variable expressivity
- 92โ95% with MFS have identifiable FBN1 mutation
- 50% inheritance risk from affected parent
โ ๏ธ RISK FACTORS
- Hypertension
- Increased BMI โ higher aortic dissection risk
โ๏ธ ASSOCIATED CONDITIONS
- MVP, aortic regurgitation, glaucoma, cataracts
- Obstructive sleep apnea, migraines
- Ligamentous laxity, crowded teeth, striae
๐ DIAGNOSTIC CRITERIA โ Ghent II
Diagnosis made if no family history and any of the following:
๐๏ธ Aortic Root (Ao) Z โฅ 2 + EL (ectopia lentis)
๐งฌ FBN1 mutation + Ao Z โฅ 2 or EL
๐ Ao Z โฅ 2 + Systemic Score โฅ 7
Use Marfan Foundation Z-Score Calculator
๐งฎ SYSTEMIC SCORING (max: 20)
| Feature | Points |
|---|---|
| Wrist & Thumb sign | 3 |
| Wrist OR Thumb sign | 1 |
| Pectus carinatum | 2 |
| Pectus excavatum / asymmetry | 1 |
| Hindfoot valgus | 2 |
| Pes planus | 1 |
| Pneumothorax | 2 |
| Dural ectasia | 2 |
| Protrusio acetabuli | 2 |
| Reduced elbow extension | 1 |
| Arm span/height >1.05 + normal spine | 1 |
| Scoliosis or thoracolumbar kyphosis | 1 |
| โฅ3/5 facial features | 1 |
| Myopia >3D | 1 |
| Skin striae | 1 |
| MVP (all types) | 1 |
Score โฅ 7 = systemic involvement
๐งโโ๏ธ PHYSICAL EXAM FINDINGS
- Facies: Dolichocephaly, enophthalmos, malar hypoplasia, micrognathia, high-arched palate
- Skeletal: Long limbs, tall stature (arm span > height), scoliosis, flat feet, joint laxity
- Thumb/Wrist Sign: Positive indicates arachnodactyly
- Skin: Striae without weight change/pregnancy
- Eyes: Ectopia lentis (upward temporal), myopia
- Chest wall: Pectus carinatum/excavatum
๐ DIFFERENTIAL DIAGNOSIS
- MASS phenotype
- Mitral valve prolapse syndrome
- Ectopia lentis syndrome
- Loeys-Dietz syndrome
- Homocystinuria (โIQ, thrombosis, downward lens dislocation)
- Ehlers-Danlos, Shprintzen-Goldberg, Fragile X
๐ฌ INVESTIGATIONS
โ MOLECULAR
- FBN1 gene sequencing: Confirms diagnosis
โ IMAGING
- Echocardiogram: Ao root Z-score (Valsalva sinus), MVP
- MRI/CT: Dural ectasia, confirm Ao dimensions
- X-ray: Scoliosis (Cobb angle โฅ20ยฐ), protrusio acetabuli
โ OPHTHALMIC
- Slit-lamp exam (for EL), high myopia, retinal risk
โ OTHERS
- Urine homocysteine: Rule out homocystinuria
๐ TREATMENT
๐ MEDICAL
- ฮฒ-blockers (e.g., atenolol): Slow aortic dilation (target HR <100)
- ARBs (e.g., losartan): Option if ฮฒ-blockers contraindicated
- Avoid calcium channel blockers
- Individualize based on genotype and progression
๐งโโ๏ธ MULTIDISCIPLINARY TEAM
- Genetics, Cardiology, Orthopedics, Ophthalmology, Cardiothoracic Surgery
๐ฉบ SURGICAL INDICATIONS
CARDIOVASCULAR
- Ao root โฅ5.0 cm or increase โฅ1 cm/year โ Surgery
- Type A Ao dissection: Emergency surgery
- Type B Ao dissection: Medical or surgical based on severity
- MVP repair: Progressive MR or LV dysfunction
OPHTHALMOLOGIC
- Lens extraction: Vision loss, glaucoma, complete dislocation
ORTHOPEDIC
- Scoliosis >40ยฐ โ Surgery; bracing if 20โ40ยฐ
- Pectus excavatum: Surgery if cardio-pulmonary compromise
- Hip replacement: Later life if arthritis from acetabuli protrusion
๐ FOLLOW-UP
๐ซ CARDIOVASCULAR
- <20 yrs: Echo annually
- Stable adults: Echo every 2โ3 years
- Ao root >4.5 cm: Imaging every 6 months
๐ฆด MUSCULOSKELETAL
- Monitor scoliosis, growth velocity semiannually during growth
- Bone age: Consider HRT if delayed
๐๏ธ OPHTHALMIC
- Annual eye exams
- Prevent amblyopia in early myopia
๐ซ PULMONARY
- PFTs if respiratory symptoms or chest deformities
๐ฝ๏ธ DIET
- Homocystinuria exclusion is important: diet + B6/B12 may help if present
๐ PROGNOSIS
- With early diagnosis, monitoring, and intervention, near-normal life expectancy
- Life-threatening: Ao dissection, valvular insufficiency
โ ๏ธ COMPLICATIONS
- Ao dissection (Type A/B)
- Mitral/Aortic regurgitation
- Retinal detachment, glaucoma
- Pneumothorax
- Bacterial endocarditis
๐ CODES
- Q87.40 โ MFS, unspecified
- Q87.43 โ MFS with skeletal manifestations
- Q87.418 โ MFS with CV manifestations
๐ง CLINICAL PEARLS
- Screen tall athletes with โ arm span for aortic root
- Use Z-score calculators for Ao root indexing
- EL + Ao dilation = diagnostic anchors
- FBN1 testing is becoming central to diagnosis