Dados do Trabalho

Título

EPILEPTIC SEIZURE AS A MANIFESTATION OF CONGENITAL MYASTHENIA CAUSED BY LRP4 GENE MUTATION - PHENOTYPIC VARIABILITY OR MERE COINCIDENCE?

Apresentação do caso único

I.C.S.C,female,6 years old,was admitted to the emergency unit of the University Hospital due to a bilateral tonic-clonic epileptic seizure.On neurological examination,isolated left eyelid ptosis was observed,without other findings.When questioned,the mother reported that the child has always had a slight fluctuating left eyelid fissure asymmetry,but the ptosis became more pronounced after the first epileptic seizure.There were no complaints of muscle weakness.After the second epileptic seizure,carbamazepine (CBZ) was introduced with a good response,but due to agitation and mood swings,an attempt to switch to topiramate was unsuccessful.CBZ was continued and eventually discontinued two years after seizure control.The child had a normal neonatal screening for metabolic diseases and a history of epilepsy in the paternal grandfather.In the workup,brain MRI and electromyography were normal,with repetitive stimulation testing showing no electro-decrement.Electroencephalogram showed mild slowing of baseline activity.Whole exome sequencing revealed a heterozygous variant likely pathogenic in the LRP4 gene,ruling out the initial suspicion of mitochondrial myopathy.Treatment with pyridostigmine was initially started with transient response,later replaced by salbutamol,which showed good clinical response and is continued to date.

Discussão

Congenital myasthenia caused by mutations in the LRP4 gene is a rare neuromuscular condition.The low-density lipoprotein receptor-related protein 4 (LRP4) is crucial for the formation and maintenance of the neuromuscular junction,interacting with muscle-specific kinase (MuSK) to regulate acetylcholine receptor density.Patients with mutations in the LRP4 gene present symptoms from birth or early childhood,including muscle weakness,fatigability,ptosis, dysphagia and respiratory disorders.

Comentários finais

Congenital myasthenic syndromes encompass a highly heterogeneous group of hereditary diseases resulting from genetic mutations that impair neuromuscular transmission.With next-generation sequencing,a significant number of genes have been discovereddemonstrating clinical variability that includes findings as diverse as epilepsy,intellectual disability,cerebellar ataxia,facial dysmorphisms,congenital malformations,and epidermolysis bullosa among others,as part of the broad spectrum.However,given the rarity of the mutation found,questions about the occurrence of epilepsy in this particular case—consequence or coincidence—still remain.

Referências

1.Chen, Bai-Hui et al. “LRP4-related signalling pathways and their regulatory role in neurological diseases.” Brain research vol. 1825 (2024): 148705. doi:10.1016/j.brainres.2023.148705.
2. Carvalho, F. C., Camargo, C. C., Barbosa, T. P., Silva, M. do N., dos Reis, M. B., Ferreira, L. de C. E., Castro, L. K. C., & Sabatini, P. M. de O. (2022). Epilepsia, do diagnóstico ao tratamento: revisão de literatura / Epilepsy, from diagnosis to treatment: a literature review. Brazilian Journal of Development, 8(2), 8988–8997. https://doi.org/10.34117/bjdv8n2-038.
3. Zuberi, Sameer M, and Joseph D Symonds. “Update on diagnosis and management of childhood epilepsies.” Jornal de pediatria vol. 91,6 Suppl 1 (2015): S67-77. doi:10.1016/j.jped.2015.07.003.
4. Gomes, Marleide. (2006). História da epilepsia: um ponto de vista epistemológico. Journal of Epilepsy and Clinical Neurophysiology. 12. 10.1590/S1676-26492006000500009.

Palavras Chave

Congenital myasthenia; epilepsy; LRP4 gene