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Widening phenotypic spectrum of GABBR2 mutation

  • Debopam SamantaEmail author
  • Yuri A. Zarate
Letter to the Editor
  • 21 Downloads

Introduction

Pathogenic GABAB receptor R2 (GABBR2) mutations were described recently in patients with epileptic encephalopathy and Rett syndrome-like phenotype (Early infantile epileptic encephalopathy 59, MIM#617904) [1, 2, 3, 4, 5, 6, 7]. Here, we report a child with absence epilepsy and mild developmental delay who has a GABBR2 likely pathogenic variant. We further reviewed all electroclinical data of previously published cases to determine the phenotypic spectrum and genotype–phenotype association.

Case description

A 5-year-old boy was evaluated in the Neurology clinic with a 1-year history of intermittent episodes of inattention, staring, unresponsiveness, and rhythmic eye blinking. These episodes lasted for only a few seconds but occurred multiple times daily with no postictal behavioral or mental alteration. He never had any convulsions. He was born full-term following an uncomplicated pregnancy and delivery. Parents were nonconsanguineous. There was no family history of...

Keywords

GABBR2 Epileptic encephalopathy Rett-like phenotype Absence seizure Intellectual impairment 

Notes

Author contributions

DS wrote the first draft of the manuscript. YAZ evaluated the patient, provided genetic counseling to the family, and approved the final manuscript as submitted.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Compliance with ethical standards

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; and Epi4K Consortium (2014) De novo mutations in synaptic transmission genes including DNM1cause epileptic encephalopathies. Am J Hum Genet 95:360–370CrossRefGoogle Scholar
  2. 2.
    Hamdan FF, Srour M, Capo-Chichi JM et al (2014) De novo mutations in moderate or severe intellectual disability. PLoS Genet 10:e1004772CrossRefGoogle Scholar
  3. 3.
    Yoo Y, Jung J, Lee YN et al (2017) GABBR2 mutations determine phenotype in Rett syndrome and epileptic encephalopathy. Ann Neurol 82:466–478CrossRefGoogle Scholar
  4. 4.
    Lopes F, Barbosa M, Ameur A et al (2016) Identification of novel genetic causes of Rett syndrome-like phenotypes. J Med Genet 53:190–199CrossRefGoogle Scholar
  5. 5.
    Vuillaume ML, Jeanne M, Xue L et al (2018) A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-like phenotype. Ann Neurol 83:437–439CrossRefGoogle Scholar
  6. 6.
    Study TD. Prevalence and architecture of de novo mutations in developmental disorders. Nature 542(7642):433Google Scholar
  7. 7.
    Carneiro TN, Krepischi AC, Costa SS et al (2018) Utility of trio-based exome sequencing in the elucidation of the genetic basis of isolated syndromic intellectual disability: illustrative cases. Appl Clin Genet 11:93CrossRefGoogle Scholar
  8. 8.
    Schuler V, Lüscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C, Urban L, Fox A (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre-and postsynaptic GABAB responses in mice lacking GABAB (1). Neuron 19(1):47–58CrossRefGoogle Scholar
  9. 9.
    Benarroch EE. GABAB receptors: structure, functions, and clinical implications. Neurology 78(8):578–584Google Scholar

Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  1. 1.Section of Child Neurology, Department of PediatricsUniversity of Arkansas for Medical SciencesLittle RockUSA
  2. 2.Section of Genetics and Metabolism, Department of Pediatrics, Arkansas Children’s HospitalUniversity of Arkansas for Medical SciencesLittle RockUSA

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