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Cited by 81Genomics and Rare DiseasesDown syndrome and intellectual disability researchGenetics and Neurodevelopmental Disorders

The Genetics of Intellectual Disability

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Jansen, Sandra, Vissers, Lisenka E. L. M., de Vries, Bert B. A.·2023·Brain Sciences
DOI 10.3390/brainsci13020231PMC PMC9953898
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Abstract

Intellectual disability (ID) has a prevalence of ~2–3% in the general population, having a large societal impact. The underlying cause of ID is largely of genetic origin; however, identifying this genetic cause has in the past often led to long diagnostic Odysseys. Over the past decades, improvements in genetic diagnostic technologies and strategies have led to these causes being more and more detectable: from cytogenetic analysis in 1959, we moved in the first decade of the 21st century from genomic microarrays with a diagnostic yield of ~20% to next-generation sequencing platforms with a yield of up to 60%. In this review, we discuss these various developments, as well as their associated challenges and implications for the field of ID, which highlight the revolutionizing shift in clinical practice from a phenotype-first into genotype-first approach.

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  • Pathogenic variants within the same neurodevelopmental gene may result in diverse clinical presentations, including differences in severity.

    “Additionally, pathogenic variants within the same neurodevelopmental gene may result in diverse clinical presentations, including differences in severity125.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [125]

    The Introduction (page unavailable) says that mutations in the same gene can cause clinical variability within an intellectual-disability disorder. It does not specifically link that variability to differences in severity, and its statement concerns intellectual disability rather than neurodevelopmental disorders generally. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Jansen, S., Vissers, L. E. L. M., & de Vries, B. B. A.
Affiliations
  • Radboud University Medical Center (NL)
  • Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
ORCID
Venue
Brain Sciences
Publisher
MDPI AG
Published
2023-01-30
Volume
13
Issue
2
Pages
231
ISSN
2076-3425 (ISSN-L)
DOI
10.3390/brainsci13020231
PMC
PMC9953898
OpenAlex
W4318478389
Cited by
81
References
13
Citations by year
2026: 24 · 2025: 26 · 2024: 23 · 2023: 8
FWCI
3.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
the Dutch Organization for Health Research and Development (ZON-MW 912–12−109)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
intellectual disability, genetic causes of intellectual disability, genetic diagnosis, cytogenetic analysis, genomic microarrays, next-generation sequencing, genotype-first approach, diagnostic yield

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