Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication

Filges, Isabel; Sparagana, Steven; Sargent, Michael; Selby, Kathryn; Schlade‐Bartusiak, Kamilla; Lueder, Gregg T.; Robichaux‐Viehoever, Amy; Schlaggar, Bradley L.; Shimony, Joshua S.; Shinawi, Marwan

doi:10.1002/ajmg.a.36605

Cited by 30Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersFetal and Pediatric Neurological Disorders

Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication

Filges, Isabel, Sparagana, Steven, Sargent, Michael, Selby, Kathryn, Schlade‐Bartusiak, Kamilla, Lueder, Gregg T., Robichaux‐Viehoever, Amy, Schlaggar, Bradley L. +2 more·2014·American Journal of Medical Genetics Part A

DOI 10.1002/ajmg.a.36605

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Abstract

The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work‐up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid‐lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications. © 2014 Wiley Periodicals, Inc.

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16p11.2 duplications have reduced cortical thickness, reduced hippocampal volume, and enlarged ventricles.
“16p11.2 duplications also have the reduced cortical thickness [14, 23], reduced hippocampal volume [49] and enlarged ventricles [50, 53, 55].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [55]

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Authors: Filges, I., Sparagana, S., Sargent, M., Selby, K., Schlade‐Bartusiak, K., Lueder, G. T., Robichaux‐Viehoever, A., Schlaggar, B. L., Shimony, J. S., & Shinawi, M.
Affiliations: University of British Columbia (CA)
Texas Scottish Rite Hospital for Children (US)
Washington University in St. Louis (US)
Corresponding author: Filges, Isabel
ORCID: Filges, Isabel
Sparagana, Steven
Sargent, Michael
Selby, Kathryn
Schlade‐Bartusiak, Kamilla
Lueder, Gregg T.
Schlaggar, Bradley L.
Shimony, Joshua S.
Shinawi, Marwan
Venue: American Journal of Medical Genetics Part A
Publisher: Wiley
Published: 2014-05-28
Volume: 164
Issue: 8
Pages: 2003-2012
ISSN: 1552-4825 (ISSN-L)
1552-4833
DOI: 10.1002/ajmg.a.36605
OpenAlex: W2125688134
Cited by: 30
References: 31
Citations by year: 2025: 1 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 1
FWCI: 1.31
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: American Journal of Medical Genetics Part A (publishedVersion)
PubMed (publishedVersion)
Funders: Swiss National Science Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords: brain MRI abnormalities, ventriculomegaly, Batten disease, developmental delay, anxiety disorders, neurodevelopmental phenotype, MRI surveillance, gene overexpression, MAPK/ERK pathway, incomplete penetrance
MeSH terms: Adolescent, Brain, Child, Developmental Disabilities, Chromosomes, Human, Pair 16, Female, Humans, Magnetic Resonance Imaging, Male, Phenotype, In Situ Hybridization, Fluorescence, Facies, Polymorphism, Single Nucleotide, Comparative Genomic Hybridization, Chromosome Duplication

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Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication

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