CHD2 Geninde Denovo Heterozigot Yeni Bir Mutasyonun Saptandığı Bir Epileptik Ensefalopati Olgusu

Abstract

Epileptik ensefalopatiler (EE), çoklu nöbet tipleri, gelişimsel gecikme ve hatta gerileme ile karakterize ciddi epilepsi sendromlarıdır. CHD2'deki (kromodomain sarmal DNA bağlayıcı protein 2) patojenik varyantlar, epileptik ensefalopatilerde ve ayrıca zihinsel engellilikten atonik-miyoklonik epilepsiye kadar değişen fenotipik değişkenlik spektrumuna sahip nörogelişimsel bozukluklarda bildirilmiştir. Biz bu olgu sunumunda oğul, erkek kardeş ve anneden oluşan kalıtsal bir patojenik CHD2 varyantı ailesini rapor ediyoruz. Bu vaka, aile içinde aynı CHD2 mutasyonu ile oluşan fenotipik heterojeniteyi gösterir ve CHD2 ile ilişkili nörogelişimsel bozuklukların potansiyel kalıtsallığını doğrular.

Keywords

• Epileptik ensefalopati
• CHD2
• Nörogelişimsel Bozukluklar

A Case of Epileptic Encephalopathy with a New Denovo Heterozygous Mutation in the CHD2 Gene

Abstract

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. Pathogenic variants in CHD2 (chromodomain helicase DNA-binding protein 2) have been reported in epileptic encephalopathies and also neurodevelopmental disorders with spectrum of phenotypic variability, ranging from intellectual disability to atonic-myoclonic epilepsy. Here, we report a family of an inherited pathogenic CHD2 variant in affected son, brother and mother. This case demonstrates intrafamilial phenotypic heterogeneity and confirms potential heritability of CHD2-related neurodevelopmental disorders.

Keywords

• Epileptic encephalopathy
• CHD2
• Neurodevelopmental Disorder

References

1. Carvill, G.L, Heavin, S.B, Yendle, S.C, et al., Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1, Nature Genetics, 201, 45, 825–830.
2. Guerrini, R, Mari, F, Dravet, C, Idiopathic myoclonic epilepsies in infancy and early childhood. In: Beureau M, Genton P, Dravet C, et al., editors, Epileptic Syndromes in Infancy, Childhood and Adolescence, 5th ed., Montrouge, France, John Libbey, 2012,166.
3. Elizabeth, C, Galizia et al., CHD2 variants are a risk factor for photosensitivity in epilepsy, Brain, 2015,138, 1198-207.
4. Kay-Marie, J, Lamar, et al. ,Chromatin Remodeling Proteins in Epilepsy: Lessons From CHD2-Associated Epilepsy, Frontiers in molecular neuroscience, 2018, 11, 208.
5. Carvill, G, Helbig, I, Mefford, H, CHD2-related neurodevelopmental disorders, In R. A. Pagon, M. P. Adam, & H. H. Ardinger (Eds.), GeneReviews® [Internet], Seattle, WA: University of Washington, 2015, 1993–2021.
6. Chénier, S, Yoon, G, Argiropoulos, B, Lauzon, J, Laframboise, R, Ahn, J.W, et al., CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems, Journal of Neurodevelopmental Disorders, 2014, 6, 9.
7. O'Roak, B.J, Stessman, H.A, Boyle, E.A, Witherspoon, K.T, Martin, B, Lee, C, et al., Recurrent de novo mutations implicate novel genes underlying simplex autism risk, Nature communications, 2014, 5, 5595.
8. Suls A, Jaehn JA, Kecskes A, Weber Y, Weckhuysen S, Craiu DC, et al., De novo loss-offunction mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome, American journal of human genetics, 2013, 93, 967–75.

9. Lebrun, N, Parent, P, Gendras, J, Billuart, P, Poirier, K, Bienvenu, T, Autism spectrum disorder recurrence, resulting of germline mosaicism for a CHD2 gene missense variant, Clinical Genetics, 2017, 92, 669–70.
10. Petersen, A.K, Streff, H, Tokita, M, Bostwick, B.L, The first reported case of an inherited pathogenic CHD2 variant in a clinically affected mother and daughter, American journal of medical genetics, 2018, 176, 1667–9.