Diagnosis: Marfan Syndrome
This 17-year-old male most likely has Marfan syndrome (MFS), a connective tissue disorder that explains the constellation of pectus excavatum, scoliosis, poor vision, joint inflammation, weakness, fatigue, fainting, and low muscle mass. 1, 2
Diagnostic Approach
Primary Diagnostic Criteria
The diagnosis of MFS requires meeting specific criteria established by the American College of Medical Genetics and Genomics 2:
- Aortic root dilation (Z-score ≥ +2) PLUS ectopia lentis, OR
- Aortic root dilation PLUS pathogenic FBN1 mutation, OR
- Aortic root dilation PLUS systemic score ≥7 points, OR
- Ectopia lentis PLUS FBN1 mutation previously associated with aortic disease 2
Essential Immediate Workup
Echocardiography is mandatory to assess for aortic root dilation, which is critical for both diagnosis and mortality risk stratification 1. The fainting episodes in this patient raise concern for potential cardiovascular involvement, including mitral valve prolapse (MVP) or aortic complications 1.
Slit-lamp ophthalmologic examination with full pupillary dilation must be performed by an ophthalmologist experienced with MFS to evaluate for ectopia lentis (lens dislocation), which is a major diagnostic criterion 1. The "poor vision" described could represent myopia (nearsightedness), which is common in MFS, or ectopia lentis 1.
Systemic Features Scoring
Calculate the systemic score using the American College of Medical Genetics and Genomics criteria 2:
- Pectus carinatum = 2 points (this patient has pectus excavatum, which scores 1 point)
- Wrist AND thumb sign = 3 points (assess for arachnodactyly)
- Hindfoot deformity = 2 points
- Pneumothorax = 2 points
- Dural ectasia = 2 points
- Protrusio acetabuli = 2 points
- Scoliosis or thoracolumbar kyphosis = 1 point
- Reduced elbow extension = 1 point
- Facial features (3 of 5: dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia) = 1 point
- Skin striae = 1 point
- Myopia > 3 diopters = 1 point
- Mitral valve prolapse = 1 point
A score ≥7 points constitutes "multiple systemic features" sufficient for diagnosis when combined with aortic root dilation 2.
Clinical Features Explained
Skeletal Manifestations
The combination of pectus excavatum, scoliosis, and low muscle mass represents classic skeletal involvement in MFS 1. These features occur due to defective fibrillin-1 protein affecting connective tissue integrity 1. The skeletal features are often clinically silent and may not be apparent to the patient or family 1.
Joint Involvement
The "inflamed finger joints" likely represents joint hypermobility rather than true inflammation, which is a common feature of MFS and related connective tissue disorders 1. True inflammatory arthritis is not characteristic of MFS.
Constitutional Symptoms
Weakness, fatigue, and low muscle mass reflect the muscular hypoplasia and adipose hypoplasia characteristic of MFS 1. These symptoms are pleiotropic manifestations of the underlying fibrillin-1 defect 1.
Cardiovascular Concerns
Fainting episodes are particularly concerning and may indicate:
Critical Differential Considerations
Loeys-Dietz Syndrome (LDS)
LDS must be excluded as it carries higher risk of aortic dissection even without significant dilation 1. LDS is associated with mutations in TGFBR1 or TGFBR2 and can present with similar skeletal features 1.
MASS Phenotype
MASS phenotype (Mitral valve prolapse, Aortic root enlargement, Skeletal abnormalities, Skin striae) shares features with MFS but lacks ectopia lentis and has less severe aortic involvement 1. However, this patient's systemic symptoms suggest more than isolated MASS.
Other RASopathies
Cardio-facio-cutaneous syndrome presents with pectus excavatum, scoliosis, muscle weakness, and low muscle mass 1, but typically includes distinctive facial features and developmental delays not mentioned here.
Family History Assessment
Personally examine parents and siblings for features including scoliosis, striae atrophicae, disproportionate stature, MVP, and aortic root dilation, as these are often clinically silent 1. Obtain detailed family history regarding sudden death, aortic aneurysms, or dissections 1.
Genetic Testing
FBN1 mutation analysis should be performed if clinical criteria are not definitively met or for family planning purposes 2. A pathogenic FBN1 mutation combined with aortic root dilation is diagnostic 2.
Immediate Management Priorities
Life-Threatening Risk Mitigation
Initiate β-blocker therapy immediately for all patients with aortic root dilation or meeting diagnostic criteria for MFS 2. This reduces aortic wall stress and slows progression of aortic dilation.
Teach signs and symptoms of aortic dissection (sudden severe chest or back pain, syncope) and consider medical alert bracelet, especially if moderate-to-severe aortic root dilation is present 1.
Surveillance Protocol
- Annual echocardiography if aortic root diameter <4.5 cm in adults AND growth rate <0.5 cm/year 2
- Echocardiography every 6 months when diameter >4.5 cm OR growth rate >0.5 cm/year 2
- Complete aortic imaging (MRA or CT) starting in young adulthood 2
Surgical Indications
Prophylactic aortic root repair is indicated when 2:
- Aortic root diameter >4.5 cm with rapid growth (>1 cm/year)
- Progressive aortic regurgitation
- Aortic root diameter >5.0 cm with aortic root-to-height ratio >10
Common Pitfalls to Avoid
Do not dismiss this as isolated familial pectus excavatum or benign joint hypermobility without comprehensive cardiovascular evaluation 1. Many features of MFS occur sporadically in the general population, but the clustering of multiple features demands systematic evaluation 1.
Do not delay echocardiography even if the patient appears otherwise healthy 1. Aortic dissection can occur with minimal warning and is a leading cause of mortality in undiagnosed MFS 1.
Do not assume normal vision excludes MFS - ectopia lentis requires specialized ophthalmologic examination and may be subtle 1. Simple myopia is also common in MFS 1.