Correct Answer: A. Autosomal dominant La d
An early diastolic murmur in a tall man with a positive family history is classic for aortic regurgitation secondary to Marfan syndrome, which is caused by mutations in the FBN1 gene encoding fibrillin-1. Marfan syndrome is inherited in an autosomal dominant pattern, meaning only one mutant allele is required for phenotypic expression. The key discriminating features are: (1) the proband (6'5" tall) shows the phenotype, (2) the family pedigree demonstrates vertical transmission across generations (affected individuals in consecutive generations), (3) both males and females are equally affected, and (4) unaffected parents do not have affected children (ruling out X-linked recessive). In Indian populations, Marfan syndrome presents with skeletal features (tall stature, arachnodactyly, pectus deformities), ocular manifestations (lens dislocation, myopia), and cardiovascular complications (aortic root dilatation, aortic regurgitation, mitral valve prolapse). The early diastolic murmur reflects aortic insufficiency from aortic root dilatation—a life-threatening complication requiring beta-blockers or ARBs (per Indian guidelines) and prophylactic aortic root replacement if diameter exceeds 5.0 cm. The autosomal dominant inheritance is confirmed by the pedigree pattern showing affected individuals in every generation with no skipping, and equal sex distribution.
Why the other options are wrong
B. X-linked — X-linked inheritance (whether dominant or recessive) would show a characteristic pattern: affected males cannot pass the trait to sons (only to daughters), and affected females would have affected sons 50% of the time. The pedigree in Marfan syndrome shows affected males transmitting to both sons and daughters equally, which is incompatible with X-linked inheritance. This is the NBE trap—students may confuse Marfan with other connective tissue disorders. C. X-linked — This appears to be a duplicate of option B. X-linked inheritance is ruled out for the same reason: the pedigree pattern shows vertical transmission in both sexes without the characteristic male-to-male transmission block or skewed female-to-male ratios expected in X-linked conditions. Marfan syndrome affects males and females equally. D. Autosomal recessive — Autosomal recessive inheritance requires two mutant alleles for phenotypic expression. In the pedigree, affected individuals typically have unaffected parents (who are carriers), and siblings of affected individuals have a 25% recurrence risk. Marfan syndrome shows affected individuals in consecutive generations with affected parents, which is inconsistent with autosomal recessive inheritance. Recessive conditions skip generations; dominant conditions do not.
High-Yield Facts
- Marfan syndrome is caused by FBN1 gene mutations and inherited as autosomal dominant with 100% penetrance but variable expressivity.
- Early diastolic murmur in Marfan syndrome indicates aortic regurgitation from aortic root dilatation, the leading cause of sudden cardiac death in young patients.
- Pedigree pattern for autosomal dominant: vertical transmission, affected individuals in every generation, both sexes equally affected, no male-to-male transmission block.
- Indian management: Beta-blockers (propranolol) or ARBs (losartan) slow aortic root dilatation; prophylactic aortic root replacement indicated when diameter ≥5.0 cm (or ≥4.5 cm if family history of dissection).
- Tall stature + arachnodactyly + lens dislocation + aortic regurgitation = Marfan syndrome until proven otherwise in Indian clinical practice.
Mnemonics
MARFAN Inheritance Male-to-male transmission present → Autosomal (not X-linked); Recurrent in every generation → Familial dominant (not recessive); Affected parents have affected children; No skipping of generations. Dominant vs Recessive Pedigree Dominant = vertical transmission, every generation, affected × unaffected → 50% affected children. Recessive = horizontal transmission (siblings), skips generations, unaffected parents → 25% affected children.
NBE Trap
NBE pairs tall stature with X-linked inheritance to trap students who confuse Marfan syndrome with X-linked conditions like Duchenne muscular dystrophy or hemophilia. The key discriminator is the pedigree pattern: Marfan shows vertical transmission in both sexes without male-to-male transmission block, which is pathognomonic for autosomal dominant inheritance.
Clinical Pearl
In Indian practice, any tall young patient presenting with an early diastolic murmur should raise suspicion for Marfan syndrome. Echocardiography to measure aortic root diameter is mandatory; if ≥5.0 cm, prophylactic aortic root replacement (Bentall procedure) is indicated to prevent life-threatening aortic dissection—a common cause of sudden cardiac death in undiagnosed Marfan patients.
_Reference: Robbins Ch. 5 (Genetic Disorders); Harrison Ch. 431 (Marfan Syndrome); KD Tripathi Ch. 3 (Genetics)_