Does It Run in Families Like a Single Gene?

First, a textbook autosomal dominant family (a contrast case, like a Van der Woude family): an affected grandfather, an affected parent, and affected children, with someone affected in EVERY generation, parent to child, in both sexes. Now Mateo's actual family: unaffected grandparents, two unaffected parents, an unaffected sister, and only Mateo affected as the proband, with one distant great-uncle as an unconfirmed "?". Counting Mateo's family, there is only ONE confirmed affected person, with two unaffected parents above him and no vertical, generation-after-generation pattern.

Geneticists carry two mental models. Clean autosomal dominant: one altered copy of a single gene is enough, and the signature is vertical transmission, an affected person in almost every generation. Two unaffected parents rarely produce it. Multifactorial (threshold) model: there is no single controlling gene; many small genetic and environmental factors add up into a total liability, and a cleft appears only when that total crosses a threshold. Most cases are sporadic (one affected person, unaffected parents), risk to relatives is modestly raised but not 50%, and the trait does NOT march cleanly down the generations. About 70% of clefts follow this model.