Our earlier family history studies of individuals with autism found a high incidence of major affective disorder, especially bipolar disorder, and unusual talents or intellectual abilities among family members. We now describe a subgroup of such families, selected from a large clinical experience, illustrating specific features of major affective disorder, special talents or intellectual ability, and familial patterns of trait transmission, with the additional feature of oculocutaneous albinism in some cases. These observations, suggesting parent-of-origin and gain-of-function effects, considered together with recent genetic findings in the literature, suggest a genetic hypothesis possibly unifying disparate observations found in families of individuals with autism.