John Libbey Eurotext

ATP6V1B2-related epileptic encephalopathy Volume 22, numéro 3, June 2020


  • ATP6V1B2-related epileptic encephalopathy


  • Figure 1
  • Figure 2
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1 Epilepsy Clinic, Hospital Sírio-Libanês,
2 Department of Neurology, University of São Paulo School of Medicine,
3 Mendelics Genomic Analysis,
4 Radiology Department, Hospital Sírio-Libanês, São Paulo, Brazil
* Correspondence: Luciana Midori Inuzuka Department of Neurology, University of São Paulo School of Medicine, Rua Haddock Lobo, 131, cj 1309, São Paulo, 01414-001, Brazil

ATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acid hydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy (DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants).

Herein, we report a case of an infant with severe epileptic encephalopathy with microcephaly and profound developmental delay, associated with a novel de novo loss-of-function variant in ATP6V1B2, diagnosed by whole-exome sequencing. This finding expands the spectrum of ATP6V1B2-associated disorders and adds ATP6V1B2 as a new member for the growing list of early-onset epileptic encephalopathy genes. [Published with video sequence].