The term “fetal alcohol spectrum disorders” (FASD) defines the full range of ethanol (EtOH)-induced birth defects. Numerous variables influence the phenotypic outcomes of embryonic EtOH exposure. Among these variables, genetics appears to play an important role, yet our understanding of the genetic predisposition to FASD is still in its infancy. We review the current literature that relates to the genetics of FASD susceptibility and gene–EtOH interactions. Where possible, we comment on potential mechanisms of reported gene–EtOH interactions. Early indications of genetic sensitivity to FASD came from human and animal studies using twins or inbred strains, respectively. These analyses prompted searches for susceptibility loci involved in EtOH metabolism and analyses of candidate loci, based on phenotypes observed in FASD. More recently, genetic screens in animal models have provided an additional insight into the genetics of FASD. Understanding FASD requires that we understand the many factors influencing phenotypic outcome following embryonic EtOH exposure. We are gaining ground on understanding some of the genetics behind FASD, yet much work remains to be carried out. Coordinated analyses using human patients and animal models are likely to be highly fruitful in uncovering the genetics behind FASD.
Normal genetic variation contributes to an individual's susceptibility to prenatal ethanol exposure. For example, if mice lacking one copy of sonic hedgehog (Shh), a key developmental signal, are exposed to ethanol during early gestation, the incidence and severity of birth defects are greatly increased (arrow in figure denotes an abnormal, flat philtrum and observe the complete lack of eyes). This review discusses what we know about the myriad genes that are known to alter sensitivity to prenatal ethanol exposure.