A clinical approach to developmental delay and intellectual disability

Vasudevan, Pradeep; Suri, Mohnish

doi:10.7861/clinmedicine.17-6-558

Cited by 72 publications

(56 citation statements)

References 4 publications

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“…ID is one type of the generalized NDDs characterized by significant impairment of intellectual (such as learning and reasoning) and adaptive functioning (activities for daily living, such as communication and independent living) (129). It is a heterogeneous disorder with regard to its clinical and genetic characteristics (130).…”

Section: Involvement Of C 2 H 2 -Znfs In Idmentioning

confidence: 99%

C2H2-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders: Systematic Literature-Based Analysis

2020

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Neurodevelopmental disorders (NDDs) are multifaceted pathologic conditions manifested with intellectual disability, autistic features, psychiatric problems, motor dysfunction, and/or genetic/chromosomal abnormalities. They are associated with skewed neurogenesis and brain development, in part through dysfunction of the neural stem cells (NSCs) where abnormal transcriptional regulation on key genes play significant roles. Recent accumulated evidence highlights C 2 H 2-type zinc finger proteins (C 2 H 2-ZNFs), the largest transcription factor family in humans, as important targets for the pathologic processes associated with NDDs. In this review, we identified their significant accumulation (74 C 2 H 2-ZNFs: ∼10% of all human member proteins) in brain physiology and pathology. Specifically, we discuss their physiologic contribution to brain development, particularly focusing on their actions in NSCs. We then explain their pathologic implications in various forms of NDDs, such as morphological brain abnormalities, intellectual disabilities, and psychiatric disorders. We found an important tendency that poly-ZNFs and KRAB-ZNFs tend to be involved in the diseases that compromise gross brain structure and human-specific higher-order functions, respectively. This may be consistent with their characteristic appearance in the course of species evolution and corresponding contribution to these brain activities.

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Section: Involvement Of C 2 H 2 -Znfs In Idmentioning

confidence: 99%

C2H2-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders: Systematic Literature-Based Analysis

2020

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“…TGP tests via NGS may be preferable choice for establishing a genetic diagnosis of DD/ID. 20) Studies have suggested TGP as the first-tier testing approach compared with WES for several diseases based on diagnostic rate, coverage, depth, and cost reduction. [21][22][23][24][25] TGP produces a diagnostic rate similar to that of WES, while recent reports showed the efficacy of NGS testing for specific neurologic diseases.…”

Section: Targeted Gene Panelsmentioning

confidence: 99%

Genetic tests by next-generation sequencing in children with developmental delay and/or intellectual disability

Han

Lee

2020

Clin Exp Pediatr

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Developments in next-generation sequencing (NGS) techogies have assisted in clarifying the diagnosis and treatment of developmental delay/intellectual disability (DD/ID) via molecular genetic testing. Advances in DNA sequencing technology have not only allowed the evolution of targeted panels but also, and more currently enabled genome-wide analyses to progress from research era to clinical practice. Broad acceptance of accuracy- guided targeted gene panel, whole-exome sequencing (WES), and whole-genome sequencing (WGS) for DD/ID need prospective analyses of the increasing cost-effectiveness versus conventional genetic testing. Choosing the appropriate sequencing method requires individual planning. Data are required to guide best-practice recommendations for genomic testing, regarding various clinical phenotypes in an etiologic approach. Targeted panel testing may be recommended as a first-tier testing approach for children with DD/ID. Family-based trio testing by WES/WGS can be used as a second test for DD/ ID in undiagnosed children who previously tested negative on a targeted panel. The role of NGS in molecular diagnostics, treatment, prediction of prognosis will continue to increase further in the coming years. Given the rapid pace of changes in the past 10 years, all medical providers should be aware of the changes in the transformative genetics field.

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“…1. 9,11) The first step in increasing the diagnostic yield is to clearly define the population of suspected genetic causes that have dysmorphic features, multiple anomalies, suggestive family history of a hereditary disease, and negative or ambiguous results from baseline investigations. Another important consideration is that more detailed and precise phenotypic differentiations lead to a higher diagnostic yield of genetic diagnosis.…”

Section: Wes / Wgs Higher Cost-effectivenessmentioning

confidence: 99%

“…There are still many considerations related to advanced genetic testing that continuously reclassifying variants of unknown significance and ethical issues. 11) Nonetheless, the role of NGS testing in the clinical setting is becoming more important and clinicians should be aware of its rapid changes in this genetic era. See the article "Genetic tests by next-generation sequencing in children with developmental delay and/or intellectual disability" via https://doi.org/10.3345/kjp.2019.00808.…”

Section: Wes / Wgs Higher Cost-effectivenessmentioning

confidence: 99%

Next-generation sequencing is a powerful method to enhance diagnostic yield in global developmental delay/intellectual disability

Kim

2020

Clin Exp Pediatr

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Next-generation sequencing (NGS) technologies are massively parallel DNA sequencing methods that allow faster and cheaper sequencing of nucleotides than does Sanger sequencing. 1) With the advent of NGS, nucleotide sequencing has found applications in the diagnosis of pediatric neurological disorders such as muscle disease, epilepsy, neurodegenerative disease, neurometabolic disease, and autism spectrum disorder. 2-4) In recent years, several studies on the genetic diagnosis of unexplained global developmental delay (DD) and intellectual disability (ID) have been published. 5-7) Global DD and ID have a high prevalence, affecting 1%-3% of children. 8) The diversity of phenotypical and genetical heterogeneity leads to a low diagnostic yield and insufficient clinical management. 7) When the clinical picture suggests a syndromic form of DD/ ID, a diagnostic genetic test is used to confirm or rule out chromosomal abnormalities or monogenic disorders: classical

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A clinical approach to developmental delay and intellectual disability

Cited by 72 publications

References 4 publications

C2H2-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders: Systematic Literature-Based Analysis

C2H2-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders: Systematic Literature-Based Analysis

Genetic tests by next-generation sequencing in children with developmental delay and/or intellectual disability

Next-generation sequencing is a powerful method to enhance diagnostic yield in global developmental delay/intellectual disability

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