Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

• Type of Material: Article
• Authors: Rossana L. Sanchez, Emory University; Jiong Yan, Emory University; Sarah Richards, Emory University; Gary Mierau, The Children's Hospital, Aurora; Eric P. Wartchow, The Children's Hospital, Aurora; Christin Collins, Emory University; Suma Shankar, Emory University
• Language: English
• Date: 2016-12-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ajoc.2016.07.005
• Title of Journal or Parent Work: American Journal of Ophthalmology Case Reports
• ISSN: 2451-9936
• Volume: 4
• Start Page: 50
• End Page: 53
• Grant/Funding Information: Emory, Department of Ophthalmology is supported by unrestricted RPB grant P30EY006360.
• Keywords: Epilepsy; Chromosome microarray; Next generation sequencing panel; Lysosomal storage disorder; Vision loss; Neuronal ceroid lipofuscinosis
• Research Categories: Health Sciences, Pathology; Biology, Genetics

Abstract

Purpose: To report atypical presentation of neuronal ceroid lipofuscinoses type 8 (CLN8) to the eye clinic and review clinical features of CLN8. Observations Detailed eye exam by slit lamp exam, indirect ophthalmoscopy, fundus photography, optical coherence tomography, visual fields and electroretinogram (ERG). Molecular genetic testing using Next Generation Sequencing panel (NGS) and array Comparative Genomic Hybridization (aCGH). The siblings in this study presented to the eye clinic with retinitis pigmentosa and cystoid macular edema, and a history of seizures but no severe neurocognitive deficits or regression. Genetic testing identified a c.200C  >  T (p.A67V) variant in the CLN8 gene and a deletion encompassing the entire gene. Electron microscopy of lymphocytes revealed fingerprint inclusions in both siblings. Conclusions and Importance: Pathogenic variants in CLN8 account for the retinitis pigmentosa and seizures in our patients however, currently, they do not have regression or neurocognitive decline. The presentation of NCL can be very diverse and it is important for ophthalmologists to consider this in the differential diagnosis of retinal disorders with seizures or other neurological features. Molecular genetic testing of multiple genes causing isolated and syndromic eye disorders using NGS panels and aCGH along with additional complementary testing may often be required to arrive at a definitive diagnosis.