The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation.

Giovanni Battista Dell'Isola,Elisabetta Mencaroni,Pasquale Striano,Giuseppe Di Cara,Alberto Verrotti,Antonella Fattorusso,Valerio Vinti,Giorgia Tascini

doi:10.3389/fneur.2021.780053

Giovanni Battista Dell'Isola, Elisabetta Mencaroni + Show 6 more

Open Access

https://doi.org/10.3389/fneur.2021.780053

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Abstract

Protocadherin 19 (PCDH19) gene is one of the most common genes involved in epilepsy syndromes. According to literature data PCDH19 is among the 6 genes most involved in genetic epilepsies. PCDH19 is located on chromosome Xq22.1 and is involved in neuronal connections and signal transduction. The most frequent clinical expression of PCDH19 mutation is epilepsy and mental retardation limited to female (EFMR) characterized by epileptic and non-epileptic symptoms affecting mainly females. However, the phenotypic spectrum of these mutations is considerably variable from genetic epilepsy with febrile seizure plus to epileptic encephalopathies. The peculiar exclusive involvement of females seems to be caused by a cellular interference in heterozygosity, however, affected mosaic-males have been reported. Seizure types range from focal seizure to generalized tonic-clonic, tonic, atonic, absences, and myoclonic jerks. Treatment of PCDH19-related epilepsy is limited by drug resistance and by the absence of specific treatment indications. However, seizures become less severe with adolescence and some patients may even become seizure-free. Non-epileptic symptoms represent the main disabilities of adult patients with PCDH19 mutation. This review aims to analyze the highly variable phenotypic expression of PCDH19 gene mutation associated with epilepsy.

Highlights

The latest ILAE classification [1] emphasizes the importance of an etiological classification of epilepsy to improve prognosis and, whether possible, initiate a target therapy
Epilepsy and mental retardation limited to female (EFMR) is the most frequent clinical expression of Protocadherin 19 (PCDH19) mutation, other important clinical manifestations are genetic epilepsy with febrile seizure plus (GEFS+) and epileptic encephalopathies
The broad phenotypic spectrum of PCDH19-related epilepsy has been extensively studied in recent years and has led to improved and earlier recognition of symptoms

Summary

INTRODUCTION

The latest ILAE classification [1] emphasizes the importance of an etiological classification of epilepsy to improve prognosis and, whether possible, initiate a target therapy. Proper development of neural architecture and neuronal connectivity require efficacious cell-cell interactions and alterations of protocadherins could result in severe disruption in early brain morphogenesis. It is not well known how mutations of PCDH19 lead to the development of epilepsy. The gene is highly expressed in endothelial cells and the main epileptic foci involve the limbic region, close to the periventricular region where BBB is missing. This theory could explain the seizure remission with growth thanks to the maturation of BBB [16]. This review aims to analyze the phenotypic expression of PCDH19 gene mutation associated with epilepsy

LITERATURE SEARCH

EPILEPSY AND MENTAL RETARDATION LIMITED TO FEMALE

GENETIC EPILEPSY WITH FEBRILE SEIZURES PLUS

Treatments efficacy

Findings

CONCLUSION