Genetic history, pedigree construction and inheritance patterns — branching viva

Opening question

A three-year-old boy with global developmental delay has parents who are first cousins and a maternal uncle who died in infancy. How do you construct the pedigree, and what does the shape of the family history tell you about the most likely inheritance pattern? [1] [2]

Branch 1 — reading the pattern and the recurrence risk

From this pedigree, what is the most likely inheritance pattern, and why does consanguinity sharpen the prior probability? What is the recurrence risk for the next child, and how is it modified if the parents are confirmed carriers? [2] [3]

Branch 2 — the imprinting trap

Take a related family in whom the affected child carries a deletion at 15q11-q13. How can the same deletion produce two different syndromes, and what investigation establishes the parent of origin? [2] [3]

Branch 3 — the isolated case and germline mosaicism

Now an isolated male with Duchenne muscular dystrophy and no family history. Neither parent tests positive on somatic testing. Explain germline mosaicism and its implication for the recurrence risk in future pregnancies. [4]

Closing — the counselling principle

In one sentence, what is the principle of communicating recurrence risk, and why is the counselling non-directive rather than directive? [1] [2]