Cerebral Palsy: An Overview of Etiology, Types and Comorbidities DOI Open Access
Joshua Vova

OBM Neurobiology, Journal Year: 2022, Volume and Issue: 6(2), P. 1 - 1

Published: Feb. 21, 2022

Cerebral Palsy (CP) is the most frequent cause of childhood disability. CP occurs in 1 out every 345 children United States. primarily a motor disease that result an insult to brain during prenatal or early postnatal period when still developing. not single but physical description impairments originate from multiple etiologies. This article briefly discusses etiologies, classification and management neurologic medical comorbidities are associated with CP. Proactive can assist minimizing morbidity maximizing outcomes improving quality life.

Language: Английский

Genetic Testing in Neurodevelopmental Disorders DOI Creative Commons
Juliann M. Savatt, Scott M. Myers

Frontiers in Pediatrics, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 19, 2021

Neurodevelopmental disorders are the most prevalent chronic medical conditions encountered in pediatric primary care. In addition to identifying appropriate descriptive diagnoses and guiding families evidence-based treatments supports, comprehensive care for individuals with neurodevelopmental includes a search an underlying etiologic diagnosis, primarily through genetic evaluation. Identification of etiology can inform prognosis, clarify recurrence risk, shape clinical management, direct patients condition-specific resources supports. Here we review utility testing describe three major modalities their yields - chromosomal microarray, exome sequencing (with/without copy number variant calling),

Language: Английский

Citations

154
Diagnostic Yield of Exome Sequencing in Cerebral Palsy and Implications for Genetic Testing Guidelines DOI
Pedro J. Gonzalez-Mantilla, Yirui Hu, Scott M. Myers

et al.

JAMA Pediatrics, Journal Year: 2023, Volume and Issue: 177(5), P. 472 - 472

Published: March 6, 2023

Importance Exome sequencing is a first-tier diagnostic test for individuals with neurodevelopmental disorders, including intellectual disability/developmental delay and autism spectrum disorder; however, this recommendation does not include cerebral palsy. Objective To evaluate if the yield of exome or genome in palsy similar to that other disorders. Data Sources The study team searched PubMed studies published between 2013 2022 using genetic testing terms. were analyzed during March 2022. Study Selection Studies performing at least 10 participants included. fewer than reporting variants detected by tests excluded. Consensus review was performed. initial search identified 148 studies, which 13 met inclusion criteria. Extraction Synthesis extracted 2 investigators pooled random-effects meta-analysis. Incidence rates corresponding 95% CIs prediction intervals calculated. Publication bias evaluated Egger test. Variability included assessed via heterogeneity I statistic. Main Outcomes Measures primary outcome (rate pathogenic/likely pathogenic variants) across studies. Subgroup analyses performed based on population age use exclusion criteria patient selection. Results Thirteen consisting 2612 overall 31.1% (95% CI, 24.2%-38.6%; = 91%). higher pediatric populations (34.8%; 28.3%-41.5%) adult (26.9%; 1.2%-68.8%) among used selection (42.1%; 36.0%-48.2%) those did (20.7%; 12.3%-30.5%). Conclusions Relevance In systematic meta-analysis, disorders recommended as standard care. from meta-analysis provide evidence support current evaluation

Language: Английский

Citations

50
Mendelian etiologies identified with whole exome sequencing in cerebral palsy DOI Creative Commons
Maya Chopra, Dustin L. Gable, Jamie Love‐Nichols

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2022, Volume and Issue: 9(2), P. 193 - 205

Published: Jan. 24, 2022

Abstract Objectives Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders under‐characterized. To explore genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort patients with CP. Methods We performed comprehensive phenotyping and WES on prospective individuals cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic at least one factor), masqueraders could be diagnosed but regression/progressive symptoms). characterized phenotypes, ascertained medical comorbidities, classified brain MRIs. analyzed data using an institutional pipeline. Results included 50 probands this analysis (20 females, 30 males). Twenty‐four had 20 five masquerader classification, unknown classification. Hypotonic‐ataxic subtype showed difference prevalence across classification groups ( p = 0.01). Twenty‐six percent participants (13/50) pathogenic/likely pathogenic variant 13 unique genes ECHS1 , SATB2 ZMYM2 ADAT3 COL4A1 THOC2 SLC16A2 SPAST POLR2A GNAO1 PDHX ACADM ATL1 ), including patient two ) ‐related disorder. The category highest diagnostic yield n 3/5, 60%), followed by 7/24, 29%). Fifteen 3/20) Mendelian disorder WES. Interpretation demonstrated significant clinically known factors.

Language: Английский

Citations

68
Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Cerebral Palsy DOI
Siddharth Srivastava, Sara A. Lewis, Julie S. Cohen

et al.

JAMA Neurology, Journal Year: 2022, Volume and Issue: 79(12), P. 1287 - 1287

Published: Oct. 24, 2022

There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without (cryptogenic CP). Early cohort studies report a wide range of diagnostic yields sequence variants assessed by exome sequencing (ES) and copy number (CNVs) chromosomal microarray (CMA).To synthesize the emerging genetics literature address question what percentage individuals with have genetic disorder via ES CMA.Searched articles were indexed PubMed relevant queries pertaining to ES/CMA (query date, March 15, 2022).Inclusion criteria as follows: primary research study, case series 10 or more nonrelated individuals, diagnosis, and/or CMA data used evaluation. Nonblinded review was performed.Preferred Reporting Items Systematic Reviews Meta-analyses guidelines assessing quality validity. Data extracted single observer.A separate meta-analysis performed each modality (ES, CMA). The outcome proportion/molecular yield (number patients discovered divided total cohort), evaluated proportions using random-effects logistic regression. A subgroup conducted, factor classification subgroup. forest plot display individual studies.In CP, overall among cohorts (15 study comprising 2419 from 11 articles) 23% (95% CI, 15%-34%). across cryptogenic 35% 27%-45%), compared 7% 4%-12%) (noncryptogenic In (5 294 5 5% 2%-12%).Results this systematic suggest that followed identify molecular disorders may be warranted.

Language: Английский

Citations

55
Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders DOI Open Access
Parthiv Haldipur, Kathleen J. Millen, Kimberly A. Aldinger

et al.

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 515 - 531

Published: April 20, 2022

Developmental abnormalities of the cerebellum are among most recognized structural brain malformations in human prenatal imaging. Yet reliable information regarding their cause humans is sparse, and few outcome studies available to inform prognosis. We know very little about cerebellar development, stark contrast wealth knowledge from decades research on developmental biology model organisms, especially mice. Recent show that multiple aspects development significantly differ mice even rhesus macaques, a nonhuman primate. These discoveries challenge many current mouse-centric models normal pathogenesis several neurodevelopmental phenotypes affecting cerebellum, including Dandy-Walker malformation medulloblastoma. Since we cannot what do not know, additional normative pathological data essential, new needed.

Language: Английский

Citations

45
Redefining cerebral palsies as a diverse group of neurodevelopmental disorders with genetic aetiology DOI
Clare L. van Eyk, Michael Fahey, Jozef Gécz

et al.

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(9), P. 542 - 555

Published: Aug. 3, 2023

Language: Английский

Citations

28
Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy DOI
Darcy Fehlings,

Mehdi Zarrei,

Worrawat Engchuan

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(4), P. 585 - 594

Published: March 29, 2024

Language: Английский

Citations

17
Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy DOI

Yangong Wang,

Yiran Xu,

Chongchen Zhou

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(5), P. 1395 - 1405

Published: May 1, 2024

Language: Английский

Citations

12
Genetic testing in individuals with cerebral palsy DOI Open Access
Halie May,

Jennifer A Fasheun,

Jennifer Bain

et al.

Developmental Medicine & Child Neurology, Journal Year: 2021, Volume and Issue: 63(12), P. 1448 - 1455

Published: June 10, 2021

AIM To determine which patients with cerebral palsy (CP) should undergo genetic testing, we compared the rate of likely causative variants from whole-exome sequencing in individuals and without environmental risk factors. METHOD Patients were part a convenience physician-referred cohort recruited single medical center, research was completed. Participants evaluated for following factors: extreme preterm birth, brain bleed or stroke, birth asphyxia, malformations, intrauterine infection. RESULTS A total 151 unrelated CP (81 females, 70 males; mean age 25y 7mo [SD 17y 5mo], range 3wks-72y) participated. Causative identified 14 participants (9.3%). There no significant difference diagnostic between factors (10 out 123; 8.1%) those (4 28; 14.3%) (Fisher's exact p=0.3). INTERPRETATION While diagnoses among higher than factors, not statistically at this sample size. The identification over 8% cases suggests that these might confer susceptibility to further include What paper adds is Genetic may Six genes previously associated palsy. Global developmental delay/intellectual disability positively etiology. Extreme stroke/brain hemorrhage, older are negatively

Language: Английский

Citations

51
Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants DOI Creative Commons
Sayaka Kayumi, Luis A. Pérez‐Jurado, María Palomares‐Bralo

et al.

Genetics in Medicine, Journal Year: 2022, Volume and Issue: 24(11), P. 2351 - 2366

Published: Sept. 9, 2022

Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) are the most frequent, recurrent monogenic of cerebral palsy (CP). We investigated range clinical phenotypes owing to disruptions determine association between NEDSDV CP.Genetic information from 404 individuals collectively 392 pathogenic were ascertained for study. From these, detailed 52 previously unpublished collected combined 68 published comparable information. The functional effects selected missense assessed using TOPFlash assay.The associated similar. A diagnosis CP was not significantly any set traits that defined a specific phenotypic subgroup, indicating is additional NEDSDV. Two dominant negative regulators WNT signaling, highlighting utility assay functionally assess variants.NEDSDV clinically homogeneous irrespective initial diagnoses, including CP, or entry points genetic testing.

Language: Английский

Citations

32