Dados do Trabalho

Título

EXPANDING THE PHENOTYPE OF KCNH5-RELATED ENCEPHALOPATHY

Apresentação do caso único

Developmental and epileptic encephalopathies are severe, rare neurological disorders often linked to genetic mutations, including those in the KCNH5 gene. Understanding and documenting diverse phenotypes associated with such genetic conditions can enhance early diagnosis and improve patient management.
We report a case of a 2-year-old child with no significant perinatal history, who exhibited normal neuropsychomotor development until 6 months of age. At this point, the child began experiencing clusters of epileptic spasms accompanied by developmental regression. Cranial MRI showed no abnormalities and electroencephalogram revealed hypsarrhythmic pattern. Vigabatrin therapy was introduced with limited success, followed by corticosteroids. The child's condition progressed with pharmacoresistant multifocal seizures (tonic, atonic, myoclonic, and focal motor), movement disorder characterized by upper limbs chorea and global developmental delay. The patient is currently receiving multidisciplinary care, including nephrology investigation of central respiratory alkalosis with compensatory metabolic acidosis. A notable improvement in seizure control was observed with the introduction of valproic acid. Whole-exome sequencing identified a de novo variant in the KCNH5 gene (c.304+2delT), with moderate pathogenicity due to its low frequency in population databases.

Discussão

Patients with pathogenic variants in the KCNH5 gene exhibit a wide range of phenotypes, from mild developmental delay to epileptic encephalopathies. Gain-of-function mutations in the KCNH5 gene may contribute to neuronal hyperexcitability, leading to epileptic seizures. The clinical presentation typically begins between 4 to 10 months of age, along with normal neuroimaging. The seizure types described in the literature include focal or bilateral tonic-clonic. In the reported patient, the description allows for the expansion of phenotypes, as there are compatible characteristics, but with previously undescribed features, including infantile epileptic spasms syndrome and metabolic acidosis secondary to hyperventilation.

Comentários finais

Advances in genetic research are revealing a broader array of phenotypes linked to genetic epilepsies. This case expands the recognized phenotypes of KCNH5-related epileptic encephalopathy, illustrating the condition’s potential to include infantile epileptic spasms syndrome and hyperventilation with secondary metabolic acidosis.

Referências

HUANG, Sheng et al. Clinical phenotypes of developmental and epileptic encephalopathy-related recurrent KCNH5 missense variant p.R327H in Chinese children. Epilepsy & Behavior Reports, v. 26, p. 100671, 2024. Disponível em: https://doi.org/10.1016/j.ebr.2024.100671. Acesso em 21/07/2024.

Palavras Chave

KCNH5; Infantile Epileptic Spasms Syndrome; Developmental and epileptic encephalopathy