A 7-year-old boy presents with jaundice, mild anaemia, and splenomegaly. His father and paternal grandfather are similarly affected, and his father's brother is unaffected. The pedigree shows affected individuals in every generation with clear male-to-male transmission. A peripheral blood smear shows spherocytes, and the direct Coombs test is negative. The EMA binding test confirms the diagnosis. Which inheritance pattern, marked as **A** in the pedigree diagram, best explains this family's presentation of hereditary spherocytosis?
A. Autosomal dominant with male-to-male transmission
B. Y-linked
C. X-linked dominant
D. Autosomal recessive
Explanation
Why Autosomal dominant with male-to-male transmission is right
Hereditary spherocytosis (HS) follows autosomal dominant inheritance in approximately 75% of cases. The key diagnostic feature of autosomal dominant inheritance in this pedigree is the presence of affected individuals in every generation, male-to-male transmission (father to son), and approximately equal male-to-female involvement. The structure marked A represents this pattern. The clinical presentation—jaundice, splenomegaly, spherocytes on smear, negative direct Coombs test, and positive EMA binding test—is entirely consistent with autosomal dominant HS. Each child of an affected parent has a 50% risk of inheritance, which matches the family history described (father and grandfather affected, but uncle unaffected). Male-to-male transmission definitively excludes X-linked inheritance, which is the critical distinguishing feature here.
Why each distractor is wrong
Autosomal recessive: Autosomal recessive HS accounts for only ~25% of cases and typically presents with more severe clinical manifestations. Recessive inheritance would require both parents to be carriers or affected; the pedigree shows clear paternal transmission through males across generations, inconsistent with recessive inheritance.
X-linked dominant: X-linked dominant inheritance would NOT show male-to-male transmission. An affected father cannot pass an X-linked trait to his sons (sons receive the Y chromosome from the father). The presence of father-to-son transmission in this pedigree excludes X-linked inheritance entirely.
Y-linked: Y-linked inheritance would affect ALL sons of an affected father and NO daughters. The pedigree does not indicate that all sons are affected or that daughters are spared, making Y-linked inheritance implausible. Additionally, Y-linked disorders are extremely rare and would not account for the variable clinical severity seen in HS.
High-YieldNEET PG
Male-to-male transmission is pathognomonic for autosomal dominant (or Y-linked) inheritance and excludes X-linked patterns—this is the single most useful pedigree feature to identify autosomal dominant HS.
Harrison's 21e Ch 99; Nelson 21e Ch 485
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