Autosomal Recessive Inheritance
The inheritance pattern described is autosomal recessive (Answer A), as evidenced by the 25% risk for two carrier parents to have an affected child and the increased risk with consanguinity.
Key Genetic Principles
The clinical scenario presents classic hallmarks of autosomal recessive inheritance:
25% recurrence risk occurs when both parents are heterozygous carriers of a mutation on an autosome, with each child having a 25% chance of being affected (homozygous), 50% chance of being a carrier (heterozygous), and 25% chance of being unaffected 1
Consanguinity increases risk because related individuals are more likely to carry the same recessive mutation, dramatically increasing the probability that both parents will be carriers and that offspring will inherit two copies of the mutated gene 2, 1
Both parents are obligate carriers but typically remain asymptomatic, as heterozygous individuals do not manifest disease in autosomal recessive conditions 2
Why Other Inheritance Patterns Don't Fit
Autosomal dominant inheritance would show:
- 50% risk to offspring when one parent is affected (not 25%) 2
- Vertical transmission pattern with affected individuals in multiple generations
- No particular association with consanguinity
X-linked recessive inheritance would show:
- Predominantly affected males
- Carrier females typically unaffected
- Risk patterns dependent on sex of offspring (not uniform 25%)
- No increased risk with consanguinity in the same manner
X-linked dominant inheritance would show:
- Affected females and males in pedigree
- 50% risk to offspring (not 25%) 2
- Often more severe or lethal in males
Clinical Context
Multiple genetic conditions demonstrate this autosomal recessive pattern with increased consanguinity risk, including inherited mismatch repair deficiency (CMMRD), where "a high rate of consanguinity is observed especially among homozygous cases" 2, and various malformations of cortical development where "caution especially in families with consanguinity; recessive inheritance has been reported" 2.