Disorders of Nervous System Development

Stable Identifier
R-HSA-9697154
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Disorders of Nervous System Development
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Neurodevelopmental disorders are chronic disorders that affect the function of the central nervous system (CNS) and impair motor skills, cognition, communication and/or behavior. While these disorders frequently stem from mutations in genes that directly control CNS development, they can also be a consequence of environmental insults such as hypoxic/ischemic injury, trauma, exposure to toxins, infections and nutritional deficiencies, or be indirectly caused by mutations in metabolic genes (reviewed by Ismail and Shapiro 2019). Disorders of nervous system development have been traditionally classified based on phenotypic traits (clinical presentation). Molecular genetics studies have revealed, however, that indistinguishable clinical presentations may result from pathogenic variants in different genes whose protein products function in connected biological pathways. On the other hand, distinct clinical presentations may be caused by pathogenic mutations in a single gene that functions in multiple biological pathways (Desikan and Bakrovich 2018). In the future, phenotype-based classification of neurodevelopmental disorders may be replaced by a more informative pathway-based nomenclature (Desikan and Bakrovich 2018). Biological pathways frequently impaired in neurodevelopmental disorders are signal transduction pathways such as the mTOR pathway in tuberous sclerosis complex (TSC) (Wong 2019) and the RAS/RAF/MAPK pathway in RASopathies (Kang and Lee 2019), neurotransmission pathways as in some autism spectrum disorders (ASD) (Burnashev and Szepetowski 2015, Hu et al. 2016), and pathways that regulate gene expression as in Mendelian disorders of epigenetic machinery (MDEM) (Fahrner and Bjornsson 2019).

So far,we have annotated the role of loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2), an epigenetic regulator of transcription, in Rett syndrome, a pervasive developmental disorder that belongs to the MDEM category (Pickett and London 2005, Ferreri 2014).
Literature References
PubMed ID Title Journal Year
24855782 [Pervasive developmental disorders]

Ferreri, M

Rev Prat 2014
31752929 The impact of RASopathy-associated mutations on CNS development in mice and humans

Kang, M, Lee, YS

Mol Brain 2019
16254487 The neuropathology of autism: a review

Pickett, J, London, E

J. Neuropathol. Exp. Neurol. 2005
31595951 Mendelian disorders of the epigenetic machinery: postnatal malleability and therapeutic prospects

Fahrner, JA, Bjornsson, HT

Hum. Mol. Genet. 2019
31838997 The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex

Wong, M

J Neurodev Disord 2019
31116115 What are neurodevelopmental disorders?

Ismail, FY, Shapiro, BK

Curr. Opin. Neurol. 2019
25498981 NMDA receptor subunit mutations in neurodevelopmental disorders

Burnashev, N, Szepetowski, P

Curr Opin Pharmacol 2015
27818011 Human GRIN2B variants in neurodevelopmental disorders

Hu, C, Chen, W, Myers, SJ, Yuan, H, Traynelis, SF

J. Pharmacol. Sci. 2016
28806439 Hazards of Neurological Nomenclature: Observations From Neurodevelopmental and Neurodegenerative Disorders

Desikan, RS, Barkovich, AJ

JAMA Neurol 2017
Participants
Events
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as an event of
Disease
Name Identifier Synonyms
nervous system disease DOID:863
Cross References
Mondo
Authored
Orlic-Milacic, M  (2020-08-06)
Reviewed
D'Eustachio, P  (2020-08-14)
Created
Orlic-Milacic, M  (2020-08-06)
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