TY - JOUR
T1 - Pharmaco-genetically guided treatment of recurrent rage outbursts in an adult male with 15q13.3 deletion syndrome
AU - Cubells, Joseph F.
AU - Deoreo, Elizabeth H.
AU - Harvey, Philip D.
AU - Garlow, Steven J.
AU - Garber, Kathryn
AU - Adam, Margaret P.
AU - Martin, Christa Lese
PY - 2011/4/1
Y1 - 2011/4/1
N2 - 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 α7 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 α7 NChR function can ameliorate 15q13.3DS-associated rage outbursts.
AB - 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 α7 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 α7 NChR function can ameliorate 15q13.3DS-associated rage outbursts.
KW - α7 nicotinic acetylcholine receptor
KW - Acetylcholine
KW - Aggression
KW - Autism
KW - Chromosome disorders
KW - Epilepsy
KW - Mental retardation
KW - Schizophrenia
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U2 - 10.1002/ajmg.a.33917
DO - 10.1002/ajmg.a.33917
M3 - Article
C2 - 21594999
AN - SCOPUS:79953325912
VL - 155
SP - 805
EP - 810
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 4
ER -