Dados do Trabalho

Título

PCDH19-RELATED EPILEPSY: Early Infantile Epileptic Encephalopathy Type 9 (EIEE9)

Apresentação do caso

Seven-year-old female, with uncomplicated pregnancy and birth, presented normal motor and slightly delayed language development. Epilepsy onset at 15th month with febrile, focal onset (impaired awareness) to bilateral seizures, which increased in frequency, requiring hospitalization and intravenous antiseizure medications. She was discharged without seizures, using oral phenobarbital, and referred to follow up and investigation. Similar episodes of explosive clustering seizures (up to 30 times/day, refractory) triggered by fever or infection, demanding hospitalization, recurring every 6 months (8 episodes by the age 6). Between episodes she was seizure-free, showing no developmental regression or neurological deficits. Last episode occurred at age 6, during video-EEG. Currently on valproic acid, clobazam and levetiracetam. Learning and social difficulties are reported. Family history indicated a father’s uncle (and 2 of his daughters) with epilepsy. Immature speech, fine motor difficulties and some dysmorphic features were noted. Brain MRI (3T), otherwise normal, at first indicated possible left frontal cortical malformation, ruled out after further analysis. PET-CT (FDG) was also normal. VEEG revealed rare interictal discharges; only 2 registered seizures could be analyzed (clustering events and ICU transference followed), both showing focal clinical and diffuse electrographic onset. Gene panel found a likely pathogenic variant in PCDH19 gene consistent with EIEE9 (OMIM: 300088).

Discussão

EIEE9 - characterized by clustering epilepsy, fever sensible, in girls - is part of PCDH19-related spectrum. Other developmental disabilities are variably associated. This X-linked disorder affecting girls – a unique feature – is not fully understood. Symptoms resulting from abnormal interactions between two neuron populations is the current hypothesis. Seizure frequency typically reduces with age while cognitive and/or language difficulties can become prominent. Protocadherin-19 (PCDH19) is a cell-adhesion protein involved with neural proliferation and connectivity. Coexisting cortical malformations are plausible and have been reported. Genetic epilepsies and surgical treatments are not incompatible.

Comentários finais

PCDH19 mutations have become highly relevant in the genetic and neurodevelopmental fields. This atypical X-linked condition (girls affected) and a potential surgical approach are some interesting aspects of this case.

Área

GENÉTICA EM EPILEPSIA