USMLE Step 1 Question 373

Question:

A couple that is trying to conceive a child once gave birth to a baby that died at 7 months of age. This previous baby was born with severely diminished motor tone and tongue fasciculations. Autopsy revealed massive degeneration of the baby’s anterior horns, which was attributed to Werdnig-Hoffman Disease. What is the probability that another child conceived by this couple will have the same disease?

Correct Answer: B.  25%

Werdnig-Hoffman disease is inherited autosomal recessively. Since each parent is carrying one recessive allele (since one baby has already had the disease), all future children have 25% chance of being recessive homozygous for gene (B).

Werdnig-Hoffman disease is fatal at a very young age, and so is not a negative dominant trait (or the parents would have died), so 100% (E) is incorrect.

For straight-forward autosomal inheritance patterns, you could also eliminate (A) 10%, as no combination of dominant/recessive alleles (based on a Punnett-square analysis) would result in this probability.

Autosomal dominant traits are inherited at a 75% rate (D), while the heterozygous genotype is inherited at a 50% rate (C).