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Título

EPILEPTIC AND DEVELOPMENTAL ENCEPHALOPATHY ASSOCIATED WITH GABRA1 GENE MUTATION: CASE REPORT

Apresentação do caso

A.B.P., 5 years and 1 month, female, born at term, APGAR 9/10, manifested neuropsychomotor development (NPMD) delay at 8 months and, at 1 year and 3 months, after a fever, she had her first epileptic seizure, with generalized tremor. Since then, she has shown regression of NPMD milestones, self-aggression and swallowing difficulties. The seizures persisted, occurring up to 6 times a day, generalized tonic-clonic seizures and myoclonic seizures.
In the first neurological evaluation, at 1 year and 6 months, she was not very interactive, without fixing her gaze, with incomprehensible speech, right convergent strabismus, and axial and appendicular hypotonia, unable to sit without support. General laboratory tests, amino acid chromatography, urine organic acid chromatography, acylcarnitine profile and transferrin isoelectrofocalization were unaltered. Electroencephalogram detected acute left temporal waves and synchronous and symmetrical bilateral spike-wave complex burst. Genetic testing identified a pathogenic variant in the GABRA1 gene. Treatment was started with phenobarbital alone and, later, with valproic acid, without seizure control. In evolution, the association of the latter with topiramate and clobazam provided a satisfactory therapeutic response.

Discussão

The identification of a mutation in the GABRA1 gene was fundamental for a better understanding and management of the case. GABRA1 consists of one of the genes encoding the a1, b2, b3, g2 or d subunits of the GABA A receptor. This mutation, through a possible mechanism of haploinsufficiency, causes impairment of the inhibitory function of GABA, causing a wide spectrum of epilepsy phenotypes, with myoclonic and tonic-clonic seizures common features. De novo pathogenic variants are more frequent than hereditary ones. Most patients have severe childhood-onset epilepsies with associated cognitive and behavioral deficits. Also, generalized spike-wave complexes and photoparoxysmal response are often present on the EEG.

Comentários finais

The present case highlights the importance of genetic knowledge in clarifying the etiopathogenesis of epileptic and developmental encephalopathies, as well as highlighting the need for further studies for a better therapeutic approach and prognostic elucidation.

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