Rare Dravet-like epileptic encephalopathy with a novel mutation of PCDH19 gene

Abstract

Mutation in PCDH 19 gene, encoding prothocadherin 19 on chromosome Xq22, results in an epileptic syndrome with seizure onset in infancy, with or without mild to severe intellectual impairment or autistic features. This disorder demonstrates an unusual pattern of X-linked inheritance, aff ecting heterozygous female but sparing hemizygous male individuals. The underlying responsible mechanism is considered to be a ‘cellular interference’. There is a wide clinical spectrum of seizures, generally starting in infancy or early childhood. A portion of patients manifest a phenotype resembling Dravet syndrome. The seizures mostly occur in brief clusters even at mild to moderately elevated temperature. In the initial course of the disease, the seizures become relatively resistant to antiepileptic drugs. However, as the disease progresses, the frequency of seizures and their pharmacoresistance tend to decrease. There may be behavioral diffi culties such as autistic, obsessive or aggressive features. The aim of this paper is to describe clinical features and unusual way of inheritance of PCDH19 gene related epilepsy in a 10-year-old girl, with special reference to early disease characteristics and treatment effi cacy. From early childhood, this 10-year-old girl suff ered from and was treated for resistant epilepsy, clinically presenting with a series of focal motor seizures accompanied by fear and screaming. On many occasions, repeated interictal waking and sleeping EEGs, as well as high resolution brain MRI (3T) were normal. Analysis of cerebrospinal fl uid excluded infl ammatory diseases of the central nervous system. Rare metabolic diseases with epileptic seizures were excluded by metabolic tests. After the fi rst seizure, phenobarbital was recommended, and after recurrence she received therapy with multiple combinations of various antiepileptic drugs, none of which was eff ective. Complete seizure control was never achieved. Genetic analysis revealed novel heterozigous nonsence mutation (c.1630C>T;p. Q544X) in exon 1 of PCDH19 gene on Xq22.1. Therapy included perampanel with valproate and levetiracetam. The authors want to warn of this rare form of epileptic encephalopathy that aff ects only female children and to emphasize its importance in the diff erential diagnosis of uncontrolled epileptic syndromes associated with febrile conditions.