Mild Angelman syndrome phenotype due to a mosaic methylation imprinting defect

Angelman syndrome (AS) is a neurogenetic disorder causing severe to profound intellectual disability, absent or very limited speech and a high risk for seizures. AS is caused by a loss of function of the maternally-derived UBE3A allele due to one of several mechanisms including imprinting defects (ImpDs). We present a girl with AS due to a mosaic ImpD who has relatively high developmental function (VABS-II composite score of 76) and communication skills (as demonstrated in supplemental video links). Given the patient's relatively mild developmental impairment, without clinical evidence of seizures, gait disturbance or inappropriate laughter, the diagnosis of AS was not initially suspected. Initial laboratory testing for AS was inconclusive but additional studies suggested mosaic ImpD and characteristic EEG findings provided further support for the clinical diagnosis. Our patient, along with other case reports of children with AS and relatively mild phenotypes, raises the question as to whether there exists an undiagnosed group of individuals with mild intellectual disability and expressive speech delays due to mosaic methylation defects of the chromosome 15q11.2-13 region. Population studies may be needed to determine if such an undiagnosed group exists.