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 male presented to the emergency department with worsening aggression andbehavioral problems. He was diagnosed with seizure disorder at 9 months old and was started on Keppra. He also had delayed developmental milestones including failure to roll until 6 months, and failure to crawl until after 9 months. At 16 months he was aggressive towards other children including unprovoked attacks of biting and assault. When he was 6yrs old he underwent genetic testing which showed positive for PCDH19 mutation. The most consistent feature of this condition is the early onset ofseizures between 3 months to 3 years of age. He has been on nine anti-seizure medications since his diagnosis. For behavioral problems, he was placed on Focalin, Ritalin, Adderall patch which did not seem to work. He was then on non-stimulants, Zoloft, Prozac, Effexor, Zyprexa and Abilify all with little success.

During this admission, patient’s mother described increasing acts of severe physical violence toward multiple people leading to significant bruising. He has a known past psychiatric history of ASD, ADHD,ODD and PCDH19 mutation associated epilepsy. On admission, his medications included Buspirone 5mg BID, Olanzapine 7.5mg BID, Methylphenidate 7.5mg, Ritalin 7.5mg, Zonisamide 150mg qhs, Clonidine 0.1mg qhs. He had significant sensory processing difficulties and lack of communication with peers. He was continued on Clonidine 0.1mg po qhs, Methylphenidate 7.5mg po qam and at noon, Zonisamide 150mg daily. Tapered down Olanzapine and initiated him on Risperidone. His condition improved. He was referred to Thompson center for ABA therapy. He is more interactive and has a smile.

DISCUSSION

PCDH19 gene mutations have long since been known to cause epilepsy and behavioral disturbances in females. Males, on the other hand, present as asymptomatic transmitters. PCDH19 is a gene located on Chromosome X and is responsible for the formation of a protein known as protocadherin 19. This protein is especially important as it functions as a Ca2+ dependent cell adhesion in the brain. The PCDH19 mutation, however, impedes protein formation leading to epilepsy and behavioral disturbances. Approximately 90% of symptomatic females possess the mutated gene on one of their X chromosomes. Males similarly carry the mutation on their X chromosome, however are typically asymptomatic. A rare mosaic variant of PCHD19 mutations has been seen in symptomatic males.

CONCLUSION

Although it is more difficult to think in terms of ASD if a PCDH19 patient has coexisting psychiatric comorbidities like ODD andADHD, clinicians must be keenly aware of other mood disorders. Seizures do not respond well to medications. Family education, psychopharmacological treatment, ABA and CBT were successful in treating the patient. Little is known about the long-term sequela and prognosis of PCDH19 mutation in the male patient population and thus further research is warranted.

Funding Acknowledgements

No funding.