Dados do Trabalho

Título

COMPREHENSIVE GENETIC ANALYSIS IN A PEDIATRIC CASE OF INTELLECTUAL DISABILITY AND EPILEPSY: IDENTIFICATION OF PATHOGENIC GRIN2A AND PHF21A VARIANTS

Apresentação do caso único

A six-year-old girl with a history of global developmental delay, syndromic intellectual disability without a recognizable pattern and epilepsy was referred to a pediatric neurology outpatient clinic. Since nine months old, she exhibited hypotonia, delayed motor milestones, and speech difficulties. At five years old, she experienced focal seizures during sleep, diagnosed as epilepsy. Genetic testing revealed two likely pathogenic variants, in GRIN2A and PHF21A genes. The father also carried the GRIN2A variant, which was not described previously in literature, while the PHF21A variant was de novo.

Discussão

GRIN2A mutations are linked to a range of neurodevelopmental disorders, including developmental delay, epilepsy, language disorders, and neuropsychiatric issues, with a high phenotypic variability and autosomal dominant inheritance. PHF21A mutations are associated with intellectual disability, craniofacial abnormalities, hypotonia, epilepsy, and neurobehavioral problems, including autism. The presence of both GRIN2A and PHF21A variants in the patient contributes to her clinical phenotype, highlighting the complexity of genetic influences in neurodevelopmental disorders. This case emphasizes the importance of next-generation sequencing in identifying the genetic basis of intellectual disability and epilepsy, particularly when other diagnostic tests are inconclusive.

Comentários finais

This case illustrates the critical role of genetic testing in diagnosing complex neurodevelopmental disorders. The identification of pathogenic variants in GRIN2A and PHF21A genes provided a clearer understanding of the patient's condition, informing clinical management and prognosis. Genetic diagnoses enable better clinical surveillance, guide therapeutic interventions, and contribute to valuable data for genetic databases, facilitating future research and diagnosis of similar conditions. The combination of inherited and de novo mutations in this case underscores the diverse genetic landscape of intellectual disability and epilepsy, necessitating comprehensive genetic evaluation in affected individuals.

Referências

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Palavras Chave

Neurodevelopmental Delay; genetic disorder; epilepsy