Journal of Pediatric Epilepsy 2022; 11(01): 021-026
DOI: 10.1055/s-0041-1731816
Case Report

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

Evan Jiang
1   College of Arts and Sciences, The University of Pennsylvania, Philadelphia, Pennsylvania, United States
,
Mark P. Fitzgerald
2   Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
3   The Epilepsy NeuroGenetics Initiative, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
Katherine L. Helbig
2   Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
3   The Epilepsy NeuroGenetics Initiative, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
,
2   Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
3   The Epilepsy NeuroGenetics Initiative, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
4   Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States
5   Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States
› Author Affiliations
Funding This work was supported by NIH NINDS K08 NS097633 and a Burroughs Wellcome Fund Career Award for Medical Scientists to E.M.G.

Abstract

Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) encodes a protein that is highly expressed in neurons and has been shown to regulate neurite outgrowth as well as synapse formation and synaptic transmission. Clinically, mutations in or deletions of IL1RAPL1 have been associated with a spectrum of neurological dysfunction including autism spectrum disorder and nonsyndromic X-linked developmental delay/intellectual disability of varying severity. Nearly all reported cases are in males; in the few reported cases involving females, the clinical presentation was mild or the deletion was identified in phenotypically normal carriers in accordance with X-linked inheritance. Using genome-wide microarray analysis, we identified a novel de novo 373 kb interstitial deletion of the X chromosome (Xp21.1-p21.2) that includes exons 4 to 6 of the IL1RAPL1 gene in an 8-year-old girl with severe intellectual disability and behavioral disorder with a history of developmental regression. Overnight continuous video electroencephalography revealed electrical status epilepticus in sleep (ESES). This case expands the clinical genetic spectrum of IL1RAPL1-related neurodevelopmental disorders and highlights a new genetic association of ESES.

Note

This study was approved by the Institutional Review Board of the Children's Hospital of Philadelphia on November 6, 2015 (IRB protocol number: 15–012226). Informed consent was obtained from the patient's legal guardians. Informed consent for participation in this study was provided by the patient's parents.




Publication History

Received: 12 January 2021

Accepted: 09 June 2021

Publication Date:
13 July 2021 (online)

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany