Cerebral palsy and related neuromotor disorders: Overview of genetic and genomic studies DOI Creative Commons
Jan M. Friedman, Peter van Essen, Clara van Karnebeek

et al.

Molecular Genetics and Metabolism, Journal Year: 2021, Volume and Issue: 137(4), P. 399 - 419

Published: Nov. 8, 2021

Cerebral palsy (CP) is a debilitating condition characterized by abnormal movement or posture, beginning early in development. Early family and twin studies more recent genomic investigations clearly demonstrate that genetic factors of major effect contribute to the etiology CP. Most copy number variants small alterations nucleotide sequence cause CP arise as result de novo mutations, so estimate heritability on basis recurrence frequency within families substantially underestimate contributions etiology. At least 4% patients with typical have disease-causing CNVs, at 14% single indels. The rate pathogenic lesions probably than twice high among who atypical CP, i.e., neuromotor dysfunction additional neurodevelopmental abnormalities malformations, MRI findings medical history are not characteristic perinatal insult. Mutations many different loci can produce CP-like phenotype. importance minor epigenetic modifications producing multifactorial predisposition less clear. Recognizing specific an affected individual essential providing optimal clinical management. An etiological diagnosis provides "enhanced compass" improves overall well-being, facilitates access educational social services, permits accurate counseling, and, for subset such those underlying inherited metabolic disorders, may make precision therapy targets pathophysiology available. Trio exome sequencing assessment trio genome bioinformatics analysis variants, indels, clinically indicated initial workup patients, especially malformations abnormalities.

Language: Английский

Intake of High‐Calorie Diet and Phytonutrients: A New Paradigm to Treat Cerebral Palsy in Children DOI Creative Commons
Tabussam Tufail,

Huma Bader Ul Ain,

Mahwish

et al.

eFood, Journal Year: 2025, Volume and Issue: 6(1)

Published: Feb. 1, 2025

ABSTRACT Cerebral palsy (CP) encompasses neurodevelopmental disorders affecting movement and posture, arising from nonprogressive brain damage during prenatal, perinatal, or postnatal periods. Diagnosis typically occurs between ages 3 5, with symptoms including abnormal muscle tone impaired motor skills. CP's etiology is diverse, ranging genetic predispositions to perinatal complications, often exacerbated by poor nutrition. Management requires a multidisciplinary approach involving neurologists, therapists, surgeons, psychologists, social workers address impairments co‐morbidities like epilepsy, cognitive deficits, sensory impairments. Neurological rehabilitation, primarily through physical occupational therapies, forms the cornerstone of CP management. Addressing feeding difficulties, common in CP, necessitates enteral parenteral feeding, each potential complications. High‐calorie formulas offer promising strategy combat undernutrition improve outcomes. Research also explores benefits natural compounds kaempferol resveratrol, though further investigation needed.

Language: Английский

Citations

1
Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment DOI Creative Commons
Joanne Zhou, Erin E. Butler, Jessica Rose

et al.

Frontiers in Human Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: March 16, 2017

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP often made based on abnormal muscle tone or posture, a delay reaching motor milestones, presence gait abnormalities young Neuroimaging high-risk neonates and children diagnosed with have identified patterns neurologic injury associated CP, however, neural underpinnings remain largely uncharacterized. Here, we review nature brain as well neuromuscular deficits subsequent among CP. We first discuss terms mechanism, pattern, time during prenatal, perinatal, postnatal period preterm term-born Second, outline focus spastic characterized by weakness, shortened muscle-tendon unit, spasticity, impaired selective control, both microscopic functional level. Third, examine influence while considering emerging information correlates implications for strategic treatment. This basis discusses what known about links between location extent type severity relation to deficits, abnormalities. Targeted treatment opportunities are that may improve outcomes By providing this context hope highlight areas further research can reduce long-term, debilitating effects

Language: Английский

Citations

83
A Network-Based Bioinformatics Approach to Identify Molecular Biomarkers for Type 2 Diabetes that Are Linked to the Progression of Neurological Diseases DOI Open Access
Md Habibur Rahman, Silong Peng, Xiyuan Hu

et al.

International Journal of Environmental Research and Public Health, Journal Year: 2020, Volume and Issue: 17(3), P. 1035 - 1035

Published: Feb. 6, 2020

Neurological diseases (NDs) are progressive disorders, the progression of which can be significantly affected by a range common that present as comorbidities. Clinical studies, including epidemiological and neuropathological analyses, indicate patients with type 2 diabetes (T2D) have worse NDs, suggesting pathogenic links between NDs T2D. However, finding causal or predisposing factors link T2D remains challenging. To address these problems, we developed high-throughput network-based quantitative pipeline using agnostic approaches to identify genes expressed abnormally in both some shared molecular pathways may underpin ND interaction. We employed gene expression transcriptomic datasets from control disease-affected individuals identified differentially (DEGs) tissues when compared unaffected individuals. One hundred ninety seven DEGs (99 up-regulated 98 down-regulated individuals) were identified. Functional annotation revealed involvement significant cell signaling associated pathways. The overlapping (i.e., seen datasets) then used extract most GO terms. performed validation results gold benchmark databases literature searching, had been previously linked novel. Hub proteins (including DNM2, DNM1, MYH14, PACSIN2, TFRC, PDE4D, ENTPD1, PLK4, CDC20B, CDC14A) protein-protein interaction analysis not described playing role diseases. reveal transcriptional post-transcriptional regulators transcription factor (TF) interactions DEG-microRNAs (miRNAs) analysis, respectively. thus following TFs important driving our T2D/ND genes: FOXC1, GATA2, FOXL1, YY1, E2F1, NFIC, NFYA, USF2, HINFP, MEF2A, SRF, NFKB1, CREB1, SP1, HOXA5, SREBF1, TFAP2A, STAT3, POU2F2, TP53, PPARG, JUN. MicroRNAs affect include mir-335-5p, mir-16-5p, mir-93-5p, mir-17-5p, mir-124-3p. Thus, data identifies novel potential pathologies underlie comorbidity interactions, targets for therapeutic intervention. In sum, neighborhood-based benchmarking multilayer network topology methods putative biomarkers how neurological interact that, future, targeted treatment.

Language: Английский

Citations

65
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

50
Genetic investigations in cerebral palsy DOI Creative Commons
Anna Basu, Karen Low, Thiloka Ratnaike

et al.

Developmental Medicine & Child Neurology, Journal Year: 2024, Volume and Issue: 67(2), P. 177 - 185

Published: Aug. 29, 2024

Abstract The original description of cerebral palsy (CP) contained case histories suggesting that perinatal environmental stressors resulted in brain injury and neurodevelopmental disability. While there are clear associations between impact on development CP, recent studies indicate an 11% to 40% incidence monogenic conditions patients given a diagnosis CP. A genetic supports the delivery personalized medicine. In this review, we describe how Wnt pathway exemplifies our understanding pathophysiology related gene variant ( CTNNB1 ) found some children diagnosed with We cover undertaken establish baseline prevalence populations attending CP clinics. list factors indicating increased likelihood genomic diagnosis; highlight need for comprehensive, accurate, genotype–phenotype reference data set aid interpretation cohorts. also consider wider societal implications management including significance diagnostic label, benefits pitfalls diagnosis, logistics, cost.

Language: Английский

Citations

7
Uncertainties Regarding Cerebral Palsy Diagnosis DOI
Bhooma R. Aravamuthan, Darcy Fehlings, Iona Novak

et al.

Neurology Clinical Practice, Journal Year: 2024, Volume and Issue: 14(6)

Published: Aug. 16, 2024

We have established that physicians, including neurologists, variably diagnose cerebral palsy (CP) when using the most recent CP definition from 2006. also know child neurologists and neurodevelopmentalists view themselves to be optimally suited based on their training backgrounds. Therefore, reduce variability in diagnosis, our objective was elucidate uncertainties may regarding practical application of 2006 definition.

Language: Английский

Citations

6
Diagnosing cerebral palsy in full‐term infants DOI
Catherine Morgan, Michael Fahey, Bithi Roy

et al.

Journal of Paediatrics and Child Health, Journal Year: 2018, Volume and Issue: 54(10), P. 1159 - 1164

Published: Oct. 1, 2018

More than 50% of infants with cerebral palsy (CP) are born at or near term, the vast majority having pre- perinatally acquired CP. While some have a clinical history predictive CP, such as neonatal encephalopathy stroke, others no readily identifiable risk factors. Paediatricians often required to discriminate generalised motor delay from variety other diagnoses, including This paper outlines known causal pathways CP in term-born focus on differential diagnosis. Early and accurate diagnosis is important it allows prompt access early intervention during critical periods brain development. A combination taking, standard examination, neuroimaging genetic testing should be started time referral. Attention investigation common comorbidities feeding sleep difficulties, referral recommended.

Language: Английский

Citations

56
Deep brain stimulation for dystonia due to cerebral palsy: A review DOI
Antonio Emanuele Elia,

Caterina Francesca Bagella,

F. Ferrè

et al.

European Journal of Paediatric Neurology, Journal Year: 2017, Volume and Issue: 22(2), P. 308 - 315

Published: Dec. 14, 2017

Language: Английский

Citations

50
Advances in cerebral palsy biomarkers DOI
Zeynep Alpay Savasan,

Sun Kwon Kim,

Kyung Joon Oh

et al.

Advances in clinical chemistry, Journal Year: 2020, Volume and Issue: unknown, P. 139 - 169

Published: May 23, 2020

Language: Английский

Citations

40
Variability in Cerebral Palsy Diagnosis DOI Open Access
Bhooma R. Aravamuthan, Darcy Fehlings, Sheetal Shetty

et al.

PEDIATRICS, Journal Year: 2021, Volume and Issue: 147(2)

Published: Jan. 5, 2021

BACKGROUND: Cerebral palsy (CP) is the most common childhood motor disability. The emergence of genetic CP etiologies, variable inclusion hypotonic in international registries, and involvement different medical disciplines diagnosis can promote diagnostic variability. This variability could adversely affect patients’ understanding their symptoms access to care. Therefore, we sought determine presence extent practice diagnosis. METHODS: We surveyed physicians United States Canada interested on basis membership American Academy Palsy Developmental Medicine or Child Neurology Society Neonatal Neurology, Movement Disorders, Neurodevelopmental Disabilities Special Interest Groups. survey included 2007 consensus definition 4 hypothetical case scenarios. RESULTS: Of 695 contacted physicians, 330 (47%) completed survey. Two scenarios yielded consensus: (1) nonprogressive spastic diplegia after premature birth with periventricular leukomalacia brain MRI (96% would diagnose CP) (2) progressive (92% not CP). Scenarios featuring etiologies hypotonia as cause disability variability: only 46% 67% practitioners these settings. CONCLUSIONS: There whether a child due etiology generalized will be diagnosed CP. occurred despite anchoring questions On results, have suggested ways reduce variability, including clarification definition.

Language: Английский

Citations

36