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Título

COMPLEX ENCEPHALOPATHY ASSOCIATED TO MUTATION IN THE GRIN2B GENE: CASE REPORT

Apresentação do caso

17-year-old female patient, single child of non-consanguineous healthy parents. The pregnancy and delivery were uneventful. She presented a normal psychomotor development until 4 months of age, when she started with epileptic seizures and evolved with central hypotonia, appendicular hypertonia, and dystonia. After, she presented autistic features, stereotypies, lack of response to pain, self-harm and did not develop speech. The epileptic seizures were refractory, with different seizures types: absence, myoclonic, tonic, tonic-clonic and gellastic seizures. In the first year of life the EEG revealed disorganization of the background activity predominating in the left cerebral hemisphere and multifocal epileptogenic activity. Video-EEG showed focal epileptic seizures with interictal discharges of generalized projection and predominance to the left, not associated with the abnormal movements presented by the patient. Complementary tests were normal including karyotype, molecular study for Rett Syndrome, Angelman and screening for IEM. Serial MRI scans of the brain revealed mild brain atrophy. Genetic study by NGS revealed a heterozygous mutation in the GRIN2B gene; which promotes the substitution

Discussão

Heterozygous pathogenic variants in the GRIN2B gene were initially associated to two main phenotypes: autosomal dominant intellectual disability (ID) 6 and epileptic and developmental encephalopathy 27. However, more recent studies show a broadening of the phenotype, including movement disorders, microcephaly and malformation of cortical development in addition to ID and epilepsy, compatible to an encephalopathy with different manifestations. The mutation (p.Gly820Ala) was previously described in the literature and it is associated with different clinical manifestations, either alone or in combination. In the present study, this mutation was associated with a broad spectrum of manifestations: severe ID without speech acquisition, refractory epilepsy, movement disorder (dystonia) and behavioral disorder.

Comentários finais

The manifestations of the GRIN2B gene overlap with those described in different genes linked to neurodevelopment disorders, highlighting the importance of using NGS in the definitive diagnosis, which allows a more adequate family counseling.

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Área

Neurogenética