181 Triple Trouble: A Rare Case Report of PCDH19, Autism and Epilepsy in a 7-Year-Old Male Child

Abstract

Background: A 7-year-old Caucasian malepresented to the emergency department with worseningaggression andbehavioral problems. He was diagnosedwith seizure disorder at 9 months old and was started onKeppra. He also had delayed developmental milestonesincluding failure to roll until 6 months, and failure tocrawl until after 9 months. At 16 months he was aggressivetowards other children including unprovoked attacks ofbiting and assault. When he was 6yrs old he underwentgenetic testing which showed positive for PCDH19mutation. The most consistent feature of this conditionis the early onset ofseizures between 3 months to 3 years ofage. He has been on nine anti-seizure medications sincehis diagnosis. For behavioral problems, he was placed onFocalin, Ritalin, Adderall patch which did not seem towork. He was then on non-stimulants, Zoloft, Prozac,Effexor, Zyprexa and Abilify all with little success.During this admission, patient's mother describedincreasing acts of severe physical violence toward multiplepeople leading to significant bruising. He has a knownpast psychiatric history of ASD, ADHD,ODD andPCDH19 mutation associated epilepsy. On admission,his medications included Buspirone 5mg BID, Olanzapine7.5mg BID, Methylphenidate 7.5mg, Ritalin 7.5mg,Zonisamide 150mg qhs, Clonidine 0.1mg qhs. He hadsignificant sensory processing difficulties and lack ofcommunication with peers. He was continued on Clonidine 0.1mg po qhs, Methylphenidate 7.5mg po qam and atnoon, Zonisamide 150mg daily. Tapered down Olanzapineand initiated him on Risperidone. His conditionimproved. He was referred to Thompson center for ABAtherapy. He is more interactive and has a smile.DISCUSSION: PCDH19 gene mutations have long sincebeen known to cause epilepsy and behavioral disturbances in females. Males, on the other hand, present asasymptomatic transmitters. PCDH19 is a gene located onChromosome X and is responsible for the formation of aprotein known as protocadherin 19. This protein isespecially important as it functions as a Ca2+ dependentcell adhesion in the brain. The PCDH19 mutation,however, impedes protein formation leading to epilepsyand behavioral disturbances. Approximately 90% ofsymptomatic females possess the mutated gene on oneof their X chromosomes. Males similarly carry themutation on their X chromosome, however are typicallyasymptomatic. A rare mosaic variant of PCHD19 mutations has been seen in symptomatic males.CONCLUSION: Although it is more difficult to think in termsof ASD if a PCDH19 patient has coexisting psychiatriccomorbidities like ODD andADHD, clinicians must bekeenly aware of other mood disorders. Seizures do notrespond well to medications. Family education, psychopharmacological treatment, ABA and CBT were successfulin treating the patient. Little is known about the long-termsequela and prognosis of PCDH19 mutation in the malepatient population and thus further research is warranted.