Pharmaco-Genetically Guided Treatment of Recurrent Rage Outbursts in an Adult Male With 15q13.3 Deletion Syndrome

15q13.3 deletion syndrome (15q13.3DS) is a common recurrent genomic disorder associated with epilepsy, intellectual impairment, aggressive behavior, schizophrenia, and autism. A 39-year-old male presented with 15q13.3DS, epilepsy, intellectual impairment, psychosis, and recurrent episodes of aggressive rage. We hypothesized that the patient's aggressive behavior reflected deficits in alpha 7 nicotinic cholinergic receptor (NChR)-mediated neurotransmission, arising from haploinsufficiency of the structural gene CHRNA7 due to the deletion. Treatment with the NChR allosteric modulator and acetylcholinesterase (AChE) inhibitor, galantamine, led to a dramatic decline in the frequency and intensity of rage outbursts, suggesting that enhancement of alpha 7 NChR function can ameliorate 15q13.3DS-associated rage outbursts. (C) 2011 Wiley-Liss, Inc.