A 28-year-old Indian couple from Odisha, both phenotypically healthy, present for genetic counselling after the birth of their first child with severe sickle cell disease (HbSS). The pedigree pattern shown in the diagram is labeled **A**, representing autosomal recessive inheritance with two carrier parents. What is the recurrence risk for an affected homozygous child in their next pregnancy?

Why 25% (1 in 4) is right

The pattern marked A in the diagram represents the classic autosomal recessive inheritance of sickle cell disease. Both parents are phenotypically unaffected heterozygotes (HbAS — sickle cell trait carriers), each carrying one mutant HBB allele (GTG at codon 6 on chromosome 11p15.5) and one normal allele. When two heterozygous parents mate, Mendelian genetics predicts: 25% homozygous normal (HbAA), 50% heterozygous carriers (HbAS), and 25% homozygous affected (HbSS). Each pregnancy is an independent event, so the recurrence risk remains 25% regardless of prior affected children. This is the fundamental principle taught in Nelson Textbook of Pediatrics and Harrison's Principles of Internal Medicine for autosomal recessive conditions.

Why each distractor is wrong

Nelson Textbook of Pediatrics 21e Ch 489; Harrison's Principles of Internal Medicine 21e Ch 99