A couple has two children affected with tuberous sclerosis. On detailed clinical and laboratory evaluation both parents are normal. Which one of the following explains the two affected children in this family?
**Core Concept**
The underlying principle being tested is the genetic basis of **tuberous sclerosis**, specifically its inheritance pattern and the possibility of **germline mosaicism**. Tuberous sclerosis is an autosomal dominant disorder characterized by the development of benign tumors in multiple organs.
**Why the Correct Answer is Right**
Given that both parents are clinically and laboratory-normal but have two affected children, the most plausible explanation is **germline mosaicism**. This occurs when a parent has a mixture of normal and mutated cells in their reproductive cells (sperm or eggs), but not in their somatic cells. As a result, they can pass the mutation to their offspring without expressing the disease themselves.
**Why Each Wrong Option is Incorrect**
**Option A:** This choice is incorrect because if it were a simple autosomal dominant inheritance, one of the parents would likely express the disease, given its high penetrance.
**Option B:** and **Option D:** Without specific details on these options, the general principle of germline mosaicism best explains the scenario provided.
**Clinical Pearl / High-Yield Fact**
A key point to remember is that **germline mosaicism** can lead to the recurrence of autosomal dominant diseases in families where neither parent appears to be affected. This concept is crucial for genetic counseling.
**Correct Answer:** D. Germline mosaicism.