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Early Myoclonic Encephalopathy

Etiologies: Metabolic etiologies (e.g. non-ketotic hyperglyinemia (the most common), propionic acidemia, methylmalonic acidemia, sulfite oxidase deficiency, urea cycle disorders, mitochondrial disorders, Menkes disease, pyridoxine dependent epilepsy, PNPO deficiency, Zellweger syndrome and molybdenum cofactor deficiency) are the main causes of this disease. In addition, mutations in ERBB4, SIK1, SLC25A22, KCNT1, GABRB2, SETBP1, PIGA, UBA5, STXBP1 and other genes are also related to this syndrome [1-9].

Age of onset: Onset within 2 months after birth (more than half of cases have onset of seizures by 10 days of life).

Seizure characteristics: At first, mandatory seizures are migratory myoclonus (involving the distal limbs and small facial muscles, it often occurs frequently, sometimes near-continuous ). Later, there are may have focal seizures, and then some may have tonic spasm, but myoclonic seizures often persist [9-10].

EEG: Interictal: a suppression-burst pattern in the interictal period (significantly during sleep). Ictal: often no corresponding relationship between clinical seizures and discharges (migratory myoclonus); generalized bursts (generalized myoclonus); focal initial discharges (focal seizures) [11].

Brain MRI: Most are normal in the early stage, but progressive cortex and periventricular atrophy may occur in the later stage [9].

Developmental progress: often severe developmental delay.

 

Note: considering that Ohtahara Syndrome and Early Myoclonic Encephalopathy have a lot of overlap in electroclinical features and have similar potential causes, further differentiation between them can no longer provide valuable information for clinical decision-making or determination of prognosis. In 2022, the international anti epilepsy Alliance (ILAE) has classified Ohtahara Syndrome and Early Myoclonic Encephalopathy into early infant developmental and epileptic encephalopathy (EIDEE) [12].

 

Diagnosis of early infant developmental and epileptic encephalopathy [12]:

Mandatory: Tonic and/or myoclonic seizures; There should be burst suppression pattern or multifocal discharge and Diffuse slowing in the interval of EEG; Onset within 3 months after birth (aadjusted for prematurity); Developmental impairment is present prior to or shortly after seizure onset; Abnormal neurodevelopment including intellectual disability.

Alerts: Normal development at onset, although it is acknowledged that this can be challenging to accurately assess historically; Normal neurological examination, although it is acknowledged that this can be challenging to assess historically or in an infant who has had very frequent seizures and/or received ASMs that may alter their exam.

 

References

  1. Backx, L., et al., Early myoclonic encephalopathy caused by a disruption of the neuregulin-1 receptor ErbB4. Eur J Hum Genet, 2009. 17(3): p. 378-82.
  2. Hansen, J., et al., De novo mutations in SIK1 cause a spectrum of developmental epilepsies. Am J Hum Genet, 2015. 96(4): p. 682-90.
  3. Cohen, R., et al., Two siblings with early infantile myoclonic encephalopathy due to mutation in the gene encoding mitochondrial glutamate/H+ symporter SLC25A22. Eur J Paediatr Neurol, 2014. 18(6): p. 801-5.
  4. Ishii, A., et al., A de novo missense mutation of GABRB2 causes early myoclonic encephalopathy. J Med Genet, 2017. 54(3): p. 202-211.
  5. McTague, A., et al., The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol, 2016. 15(3): p. 304-16.
  6. Mignon-Ravix, C., et al., Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst. Hum Mutat, 2018. 39(7): p. 934-938.
  7. Stamberger, H., et al., STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.Neurology, 2016. 86(10): p. 954-62.
  8. Gertler, T., et al., KCNT1-Related Epilepsy, in GeneReviews((R)), M.P. Adam, et al., Editors. 1993: Seattle (WA).
  9. Panayiotopoulos.  癫痫综合征及临床治疗.  北京 : 人民卫生出版社, 2012.
  10. 刘晓燕.  临床脑电图学. 第2版.  北京 : 人民卫生出版社, 2017.
  11. 李世绰.  临床诊疗指南, 癫痫病分册. 第2版.  北京 : 人民卫生出版社, 2015.
  12. Zuberi, S.M., et al., ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 2022.