Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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SLC9A6-related developmental and epileptic encephalopathy with spike-and-wave activation in sleep: A case report

  • Hye Ri Bae (Department of Pediatrics, Chonnam National University Children's Hospital) ;
  • Young Ok Kim (Department of Pediatrics, Chonnam National University Children's Hospital)
  • Received : 2022.08.28
  • Accepted : 2022.10.17
  • Published : 2022.12.31
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Abstract

The gene encoding solute carrier family 9 member 6 (SLC9A6) on Xq26.3 is associated with Christianson syndrome (CS) mimicking Angelman syndrome. In CS, developmental and epileptic encephalopathy (DEE) appears in about 20%, and DEE with spike-and-wave activation in sleep (SWAS) is reported only in several cases. A 10-year-old boy with DEE showed multidrug resistant focal seizures from 6 months of age. He had progressive microcephaly, regression, global developmental delay without speech, hyperkinesia, and truncal ataxia; he had a long thin face, esotropia, and happy demeanor. Brain magnetic resonance imaging demonstrated cerebellar atrophy. Electroencephalogram at 7.5 years of age showed nearly continuous diffuse paroxysms in slow wave sleep. The seizures were responsive to corticosteroids for a while. Trio whole exome sequencing exhibited a likely pathogenic variant of SLC9A6 in the proband and his asymptomatic mother: c.1194dup (p.Leu399AlafsTer12). This is a rare case report of CS with DEE-SWAS in a Korean patient.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Republic of Korea(grant no. NRF-2017R1D1A3A03000532).

References

  1. Specchio N, Wirrell EC, Scheffer IE, Nabbout R, Riney K, Samia P, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022;63:1398-442.  https://doi.org/10.1111/epi.17241
  2. Gardella E, Cantalupo G, Larsson PG, Fontana E, Bernardina BD, Rubboli G, et al. EEG features in encephalopathy related to status epilepticus during slow sleep. Epileptic Disord 2019;21(S1):22-30. 
  3. van den Munckhof B, Arzimanoglou A, Perucca E, van Teeseling HC, Leijten FSS, Braun KPJ, et al.; RESCUE ESES Study Group. Corticosteroids versus clobazam in epileptic encephalopathy with ESES: a European multicentre randomised controlled clinical trial (RESCUE ESES*). ESES*).  ESES*). Trials 2020;21:957. 
  4. Kessi M, Peng J, Yang L, Xiong J, Duan H, Pang N, et al. Genetic etiologies of the electrical status epilepticus during slow wave sleep: systematic review. BMC Genet 2018;19:40. 
  5. Gong P, Xue J, Jiao X, Zhang Y, Yang Z. Genetic etiologies in developmental and/or epileptic encephalopathy with electrical status epilepticus during sleep: cohort study. Front Genet 2021;12:607965. 
  6. Parsons MP, Raymond LA. Extrasynaptic NMDA receptor involvement in central nervous system disorders. Neuron 2014;82:279-93.  https://doi.org/10.1016/j.neuron.2014.03.030
  7. Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, et al. SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet 2008;82:1003-10.  https://doi.org/10.1016/j.ajhg.2008.01.013
  8. Pescosolido MF, Stein DM, Schmidt M, El Achkar CM, Sabbagh M, Rogg JM, et al. Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome. Ann Neurol 2014;76:581-93.  https://doi.org/10.1002/ana.24225
  9. Masurel-Paulet A, Piton A, Chancenotte S, Redin C, Thauvin-Robinet C, Henrenger Y, et al. A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome. Am J Med Genet A 2016;170:2103-10.  https://doi.org/10.1002/ajmg.a.37765
  10. Tan WH, Bird LM, Thibert RL, Williams CA. If not Angelman, what is it? A review of Angelman-like syndromes. Am J Med Genet A 2014;164A:975-92. 
  11. Sinajon P, Verbaan D, So J. The expanding phenotypic spectrum of female SLC9A6 mutation carriers: a case series and review of the literature. Hum Genet 2016;135:841-50.  https://doi.org/10.1007/s00439-016-1675-5
  12. Padmanabha H, Saini AG, Sahu JK, Singhi P. Syndrome of X linked intellectual disability, epilepsy, progressive brain atrophy and large head associated with SLC9A6 mutation. BMJ Case Rep 2017;2017:bcr2017222050. 
  13. Bosemani T, Zanni G, Hartman AL, Cohen R, Huisman TA, Bertini E, et al. Christianson syndrome: spectrum of neuroimaging findings. Neuropediatrics 2014;45:247-51. 
  14. Zanni G, Barresi S, Cohen R, Specchio N, Basel-Vanagaite L, Valente EM, et al. A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES). Epilepsy Res 2014;108:811-5.  https://doi.org/10.1016/j.eplepsyres.2014.02.009
  15. Mathieu ML, de Bellescize J, Till M, Flurin V, Labalme A, Chatron N, et al. Electrical status epilepticus in sleep, a constitutive feature of Christianson syndrome? Eur J Paediatr Neurol 2018;22:1124-32.  https://doi.org/10.1016/j.ejpn.2018.07.004
  16. Ikeda A, Yamamoto A, Ichikawa K, Tsuyusaki Y, Tsuji M, Iai M, et al. Epilepsy in Christianson syndrome: two cases of Lennox-Gastaut syndrome and a review of literature. Epilepsy Behav Rep 2019;13:100349. 
  17. Liu X, Xie L, Fang Z, Jiang L. Case report: novel SLC9A6 splicing variant in a Chinese boy with Christianson syndrome with electrical status epilepticus during sleep. Front Neurol 2022;12:796283. 
  18. Coorg R, Weisenberg JL. Successful treatment of electrographic status epilepticus of sleep with felbamate in a patient with SLC9A6 mutation. Pediatr Neurol 2015;53:527-31.  https://doi.org/10.1016/j.pediatrneurol.2015.07.007
  19. Rim JH, Kim SH, Hwang IS, Kwon SS, Kim J, Kim HW, et al. Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing. BMC Med Genomics 2018;11:6.