ABSTRACT
Angelman syndrome is familiar to most clinical geneticists and child neurologists as a recognizable syndrome associated with mental retardation and infantile seizures. The physician often first encounters Angelman syndrome (AS) while consulting on an infant with developmental delay, microcephaly, or seizures. The normal prenatal and birth history typically provides no clues that AS is the diagnosis. DNA methylation testing of blood is a sensitive and specific screening for three of the four known genetic mechanisms in AS. The UBE3A deficient mouse model provides some insight into regional brain dysfunction with recent work focused on the well-studied phenomenon of long-term potentiation (LTP). Learning in the context of LTP is abnormal in the AS mouse. Families with AS should be offered genetic counseling since UBE3A mutations and imprinting control defects can carry up to a 50% recurrence risk. However, the common deletion cases typically have less than 1% recurrence risk but exceptions to this can occur.
