SCN1A-related epilepsy with recessive inheritance: Ttwo further families. Moretti, R., Arnaud, L., Bouteiller, D., Trouillard, O., Moreau, P., Buratti, J., Rastetter, A., Keren, B., Des Portes, V., Toulouse, J., Gourfinkel-An, I., Leguern, E., Depienne, C., Mignot, C., & Nava, C. European Journal of Paediatric Neurology, June, 2021.
SCN1A-related epilepsy with recessive inheritance: Ttwo further families [link]Paper  doi  abstract   bibtex   6 downloads  
Background Variants in SCN1A gene, encoding the voltage-gated sodium channel Nav1.1, are associated with distinct epilepsy syndromes ranging from the relatively benign genetic epilepsy with febrile seizures plus (GEFS+) to Dravet syndrome, a severe developmental and epileptic encephalopathy (DEE). Most SCN1A pathogenic variants are heterozygous changes inherited in a dominant or de novo inheritance and many cause a loss-of-function of one allele. To date, recessive inheritance has been suggested in only two families with affected children harboring homozygous SCN1A missense variants while their heterozygous parents were asymptomatic. The aim of this report is to describe two additional families in which affected individuals have biallelic SCN1A variants possibly explaining their phenotype. Methods and results We report two novel homozygous SCN1A missense variants in two patients from related parents. Both patients had fever-sensitive epilepsy beginning in the first months of life, followed by afebrile seizures, without severe cognitive impairment. Parents were asymptomatic. Next generation sequencing excluded a pathogenic variant in other genes involved in DEE. Estimation of pathogenicity scores by in-silico tools suggests that the impact of these SCN1A variants is less damaging than that of dominant pathogenic variants. Conclusion This study provides additional evidence that homozygous variants in SCN1A can cause GEFS+. This recessive inheritance would imply that hypomorphic variants may not necessarily cause epilepsy at the heterozygous state but may decrease the seizure threshold when combined.
@article{moretti_scn1a-related_2021,
	title = {{SCN1A}-related epilepsy with recessive inheritance: {Ttwo} further families},
	issn = {1090-3798},
	shorttitle = {{SCN1A}-related epilepsy with recessive inheritance},
	url = {https://www.sciencedirect.com/science/article/pii/S1090379821001227},
	doi = {10.1016/j.ejpn.2021.05.018},
	abstract = {Background
Variants in SCN1A gene, encoding the voltage-gated sodium channel Nav1.1, are associated with distinct epilepsy syndromes ranging from the relatively benign genetic epilepsy with febrile seizures plus (GEFS+) to Dravet syndrome, a severe developmental and epileptic encephalopathy (DEE). Most SCN1A pathogenic variants are heterozygous changes inherited in a dominant or de novo inheritance and many cause a loss-of-function of one allele. To date, recessive inheritance has been suggested in only two families with affected children harboring homozygous SCN1A missense variants while their heterozygous parents were asymptomatic. The aim of this report is to describe two additional families in which affected individuals have biallelic SCN1A variants possibly explaining their phenotype.
Methods and results
We report two novel homozygous SCN1A missense variants in two patients from related parents. Both patients had fever-sensitive epilepsy beginning in the first months of life, followed by afebrile seizures, without severe cognitive impairment. Parents were asymptomatic. Next generation sequencing excluded a pathogenic variant in other genes involved in DEE. Estimation of pathogenicity scores by in-silico tools suggests that the impact of these SCN1A variants is less damaging than that of dominant pathogenic variants.
Conclusion
This study provides additional evidence that homozygous variants in SCN1A can cause GEFS+. This recessive inheritance would imply that hypomorphic variants may not necessarily cause epilepsy at the heterozygous state but may decrease the seizure threshold when combined.},
	language = {en},
	urldate = {2021-06-21},
	journal = {European Journal of Paediatric Neurology},
	author = {Moretti, Raffaella and Arnaud, Lionel and Bouteiller, Delphine and Trouillard, Oriane and Moreau, Patricia and Buratti, Julien and Rastetter, Agnès and Keren, Boris and Des Portes, Vincent and Toulouse, Joseph and Gourfinkel-An, Isabelle and Leguern, Eric and Depienne, Christel and Mignot, Cyril and Nava, Caroline},
	month = jun,
	year = {2021},
	keywords = {Alamut, Dravet syndrome, Ffebrile seizures, GEFS+, Rrecessive inheritance},
}
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