Early Infantile Epileptic Encephalopathy with a de novo variant in ZEB2 identified by exome sequencing

Natalia Babkina; Joshua L Deignan; Hane Lee; Eric Vilain; Raman Sankar; Irina Giurgea; David Mowat; John M Graham Jr

doi:10.1016/j.ejmg.2015.12.006

Early Infantile Epileptic Encephalopathy with a de novo variant in ZEB2 identified by exome sequencing

Eur J Med Genet. 2016 Feb;59(2):70-4. doi: 10.1016/j.ejmg.2015.12.006. Epub 2015 Dec 22.

Authors

Natalia Babkina¹, Joshua L Deignan², Hane Lee², Eric Vilain³, Raman Sankar⁴, Irina Giurgea⁵, David Mowat⁶, John M Graham Jr⁷

Affiliations

¹ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].
² Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Neurology, Pediatrics and Children's Discovery and Innovation Institute at Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Service de Biochimie Génétique, INSERM U955 Equipe 11, Hôpital Henri Mondor, 94000 Créteil, France.
⁶ Department of Medical Genetics, Sydney Children's Hospital, School of Women's and Children's Health, University of New South Wales, Australia.
⁷ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

PMID: 26721324
DOI: 10.1016/j.ejmg.2015.12.006

Abstract

Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures, a burst-suppression EEG pattern, and progressive disturbance of cerebral function. We present a case of EIEE associated with a de novo missense variant in ZEB2. Heterozygous truncating mutations or deletions in ZEB2 are known to cause Mowat-Wilson syndrome (MWS), which is characterized by seizures with onset in the second year of life, distinctive dysmorphic facial features and malformations that were absent in this patient. This unique case expands the range of phenotypes associated with variants in ZEB2 and indicates that this gene should be included in the molecular investigation of EIEE cases.

Keywords: Burst-suppression EEG pattern; Clinical exome sequencing; Cortical gray and white matter atrophy; Developmental delay; Infantile Epileptic Encephalopathy (EIEE); Infantile spasms; Mowat–Wilson syndrome (MWS); Seizures; ZEB2.

Publication types

Case Reports

MeSH terms

Aicardi Syndrome / diagnosis
Aicardi Syndrome / genetics*
Aicardi Syndrome / physiopathology
DNA Mutational Analysis
Electroencephalography
Exome
Facies
Hirschsprung Disease / diagnosis
Hirschsprung Disease / genetics*
Homeodomain Proteins / genetics*
Humans
Infant, Newborn
Intellectual Disability / diagnosis
Intellectual Disability / genetics*
Microcephaly / diagnosis
Microcephaly / genetics*
Repressor Proteins / genetics*
Spasms, Infantile / diagnosis
Spasms, Infantile / genetics*
Spasms, Infantile / physiopathology
Zinc Finger E-box Binding Homeobox 2

Substances

Homeodomain Proteins
Repressor Proteins
ZEB2 protein, human
Zinc Finger E-box Binding Homeobox 2

Supplementary concepts

Infantile Epileptic-Dyskinetic Encephalopathy
Mowat-Wilson syndrome