Chromodomain Helicase DNA-Binding Domain 8 (CHD8) related neurodevelopmental disorder with overgrowth: a case series and a systematic literature review on neuroradiological findings
6 affiliations
- 1Department of Diagnostic and Interventional Neuroradiology, University Hospital Tuebingen
- 2Institute of Medical Genetics and Applied Genomics, University Hospital Tuebingen
- 3Department of Neuropediatrics, General Pediatrics, Endocrinology, Diabetology, Social Pediatrics, University Children’s Hospital Tuebingen
- 4Medical Center, Faculty of Medicine, Institute of Human Genetics, University of Freiburg
- 5Department of Neurology, Medical University of Vienna
- 6Department of Neuropediatrics, Charité University Hospital Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health
Abstract
Purpose/Methods Chromodomain Helicase DNA-Binding Domain 8 (CHD8)-Related Neurodevelopmental Disorder with Overgrowth is a rare disorder, with approximately 120 cases reported to date. First, we report six cases that presented to our hospitals with intellectual disability, autism spectrum disorder and overgrowth and one related person. Second, we performed a systematic review on neuroradiological findings in people with CHD8 variants and people with submicroscopic abnormalities of the chromosomal region 14q11.2 that includes the CHD8 gene. Results Patient 1 carried a heterozygous pathogenic frameshift variant in CHD8: c.3638del, p.Gly1213Aspfs*40. Patient 2 harbors a heterozygous pathogenic missense variant in CHD8: c.5488 C > T, p.Arg1830Cys). In Patient 3 and 4 (mother and daughter) a heterozygous frameshift variant c.3343del, p.Ala1115Leufs*39 was identified and classified as variant of unknown significance (class 3). In Patient 5 we detected a splice variant in CHD8: c.2486 + 1G > A, p.? (class 4) and patient 6 carries the stop gain variant c.1540G > T, p.Glu514* (class 5). In patient 7 we found another missense variant in CHD8: c.3289 C > G, p.His1097Asp (class 4). Magnetic resonance imaging (MRI) of patients 1 and 2 revealed bilateral T2 hyperintense white matter signal alterations periventricular, in the u fibers and the deep white matter. MRI of patients 2, 5, 6 and 7 showed prominent perivascular spaces. Additionally, patients 3, 4, 5 and 6 had asymmetric low-lying cerebellar tonsils. In the systematic review, 16 of the 111 studies screened were included in the analysis. In total, neuroradiological imaging including MRI, computer tomography and ultrasound was described in 32 patients with CHD8 variants. Peculiarities were reported in 62.5% of the patients. The neuroradiological findings were highly variable, ranging from supratentorial white matter abnormalities to cerebellar findings and ventriculomegaly. Conclusions CHD8-Related Neurodevelopmental Disorder with Overgrowth can lead to various supra- and infratentorial neuroradiological findings.
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BibTeX
@article{zerweck2026chromodomain,
title = {{Chromodomain Helicase DNA-Binding Domain 8 (CHD8) related neurodevelopmental disorder with overgrowth: a case series and a systematic literature review on neuroradiological findings}},
author = {Leonie Zerweck and Kathrin Grundmann-Hauser and Christiane Kehrer and Ute Grasshoff and Andreas Tzschach and Tobias Haack and Andrea Bevot and Marco Treven and Pablo Pretzel and Till-Karsten Hauser and Martin Kehrer and Andreas Dufke and Veronka Horber and Markus Schuelke and Ulrike Ernemann and Benjamin Bender},
journal = {Journal of Rare Diseases},
year = {2026},
month = oct,
doi = {10.1007/s44162-026-00231-0},
url = {https://doi.org/10.1007/s44162-026-00231-0},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chromodomain Helicase DNA-Binding Domain 8 (CHD8) related neurodevelopmental disorder with overgrowth: a case series and a systematic literature review on neuroradiological findings
AU - Leonie Zerweck
AU - Kathrin Grundmann-Hauser
AU - Christiane Kehrer
AU - Ute Grasshoff
AU - Andreas Tzschach
AU - Tobias Haack
AU - Andrea Bevot
AU - Marco Treven
AU - Pablo Pretzel
AU - Till-Karsten Hauser
AU - Martin Kehrer
AU - Andreas Dufke
AU - Veronka Horber
AU - Markus Schuelke
AU - Ulrike Ernemann
AU - Benjamin Bender
PY - 2026
DA - 2026/10/25
JO - Journal of Rare Diseases
DO - 10.1007/s44162-026-00231-0
UR - https://doi.org/10.1007/s44162-026-00231-0
AB - Purpose/Methods Chromodomain Helicase DNA-Binding Domain 8 (CHD8)-Related Neurodevelopmental Disorder with Overgrowth is a rare disorder, with approximately 120 cases reported to date. First, we report six cases that presented to our hospitals with intellectual disability, autism spectrum disorder and overgrowth and one related person. Second, we performed a systematic review on neuroradiological findings in people with CHD8 variants and people with submicroscopic abnormalities of the chromosomal region 14q11.2 that includes the CHD8 gene. Results Patient 1 carried a heterozygous pathogenic frameshift variant in CHD8: c.3638del, p.Gly1213Aspfs*40. Patient 2 harbors a heterozygous pathogenic missense variant in CHD8: c.5488 C > T, p.Arg1830Cys). In Patient 3 and 4 (mother and daughter) a heterozygous frameshift variant c.3343del, p.Ala1115Leufs*39 was identified and classified as variant of unknown significance (class 3). In Patient 5 we detected a splice variant in CHD8: c.2486 + 1G > A, p.? (class 4) and patient 6 carries the stop gain variant c.1540G > T, p.Glu514* (class 5). In patient 7 we found another missense variant in CHD8: c.3289 C > G, p.His1097Asp (class 4). Magnetic resonance imaging (MRI) of patients 1 and 2 revealed bilateral T2 hyperintense white matter signal alterations periventricular, in the u fibers and the deep white matter. MRI of patients 2, 5, 6 and 7 showed prominent perivascular spaces. Additionally, patients 3, 4, 5 and 6 had asymmetric low-lying cerebellar tonsils. In the systematic review, 16 of the 111 studies screened were included in the analysis. In total, neuroradiological imaging including MRI, computer tomography and ultrasound was described in 32 patients with CHD8 variants. Peculiarities were reported in 62.5% of the patients. The neuroradiological findings were highly variable, ranging from supratentorial white matter abnormalities to cerebellar findings and ventriculomegaly. Conclusions CHD8-Related Neurodevelopmental Disorder with Overgrowth can lead to various supra- and infratentorial neuroradiological findings.
SN - 2731-085X
ER -