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

State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy DOI Creative Commons
Iona Novak, Catherine Morgan, Michael Fahey

et al.

Current Neurology and Neuroscience Reports, Journal Year: 2020, Volume and Issue: 20(2)

Published: Feb. 1, 2020

Abstract Purpose of Review Cerebral palsy is the most common physical disability childhood, but rate falling, and severity lessening. We conducted a systematic overview best available evidence (2012–2019), appraising using GRADE Evidence Alert Traffic Light System then aggregated new findings with our previous 2013 findings. This article summarizes interventions for preventing managing cerebral in 2019. Recent Findings Effective prevention strategies include antenatal corticosteroids, magnesium sulfate, caffeine, neonatal hypothermia. allied health acceptance commitment therapy, action observations, bimanual training, casting, constraint-induced movement environmental enrichment, fitness goal-directed hippotherapy, home programs, literacy interventions, mobility oral sensorimotor, sensorimotor plus electrical stimulation, pressure care, stepping stones triple P, strength task-specific treadmill partial body weight support weight-bearing. medical surgical anti-convulsants, bisphosphonates, botulinum toxin, toxin occupational diazepam, dentistry, hip surveillance, intrathecal baclofen, scoliosis correction, selective dorsal rhizotomy, umbilical cord blood cell therapy. Summary have provided guidance about what works does not to inform decision-making, highlighted areas more research.

Language: Английский

Citations

782
The complex aetiology of cerebral palsy DOI Open Access
Steven J. Korzeniewski, Jaime Slaughter‐Acey,

Madeleine Lenski

et al.

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(9), P. 528 - 543

Published: Aug. 13, 2018

Language: Английский

Citations

218
A Review on Recent Advances of Cerebral Palsy DOI Open Access
Sudip Paul, Anjuman Nahar, Mrinalini Bhagawati

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 20

Published: July 30, 2022

This narrative review summarizes the latest advances in cerebral palsy and identifies where more research is required. Several studies on were analyzed to generate a general idea of prevalence of, risk factors associated with, classification (CP). Different systems used for CP functional basis also analyzed. Diagnosis along with prevention techniques discussed. State-of-the-art treatment strategies Statistical distribution was performed based selected studies. Prevalence found be 2-3/1000 lives; that can correlated are gestational age birth weight. The identified preconception, prenatal, perinatal, postnatal categories. According evidence, classified into spastic (80%), dyskinetic (15%), ataxic (5%) forms. approaches clinical investigation neurological examinations include magnetic resonance imaging (MRI), biomarkers, cranial ultrasound. procedures medical surgical interventions, physiotherapy, occupational therapy, umbilical milking, nanomedicine, stem cell therapy. Technological advancements most common neuromotor disability lives. highest contributing factor prematurity being underweight. preventions diagnostic like MRI ultrasound used. Treatment cord blood nanomedicine therapy needs investigated further future apply practice. Future indicated context technological among children.

Language: Английский

Citations

99
Cerebral Palsy DOI
Abimbola Michael‐Asalu, Genevieve Taylor,

Heather Campbell

et al.

Advances in Pediatrics, Journal Year: 2019, Volume and Issue: 66, P. 189 - 208

Published: May 15, 2019

Language: Английский

Citations

124
Genetic or Other Causation Should Not Change the Clinical Diagnosis of Cerebral Palsy DOI Creative Commons
Alastair H. MacLennan, Sara A. Lewis, Andrés Moreno-De-Luca

et al.

Journal of Child Neurology, Journal Year: 2019, Volume and Issue: 34(8), P. 472 - 476

Published: April 9, 2019

High throughput sequencing is discovering many likely causative genetic variants in individuals with cerebral palsy. Some investigators have suggested that this changes the clinical diagnosis of palsy and these should be removed from diagnostic category. Cerebral a neurodevelopmental disorder diagnosed on signs, not etiology. All nonprogressive permanent disorders movement posture attributed to disturbances occurred developing fetal infant brain can described as "cerebral palsy." This definition changed, whatever cause. Reasons include stability, utility accuracy registers, direct access services, financial social support specifically offered families palsy, community understanding diagnosis. Other disorders, for example, epilepsy, changed when genomic causes are found. The remain, prompt appropriate studies subsequently subclassified by

Language: Английский

Citations

116
Current thinking in the health care management of children with cerebral palsy DOI
David Graham, Simon Paget, Neil Wimalasundera

et al.

The Medical Journal of Australia, Journal Year: 2019, Volume and Issue: 210(3), P. 129 - 135

Published: Feb. 1, 2019

Cerebral palsy is a developmental disorder of movement and posture which often associated with comorbidities. While there currently limited range evidence-based treatments that change the underlying pathology cerebral palsy, are many areas in health care professionals can natural history improve participation quality life for children this condition. Early identification has become paramount importance management it hoped will allow earlier access to interventions may Common challenges include spasticity dystonia, pain, hip surveillance, sleep feeding, swallowing nutrition. The six Fs framework (function, family, fitness, fun, friends future) provides guide developing shared goals families palsy.

Language: Английский

Citations

86
In-depth analysis reveals complex molecular aetiology in a cohort of idiopathic cerebral palsy DOI Creative Commons
Na Li, Pei Zhou, Hongmei Tang

et al.

Brain, Journal Year: 2021, Volume and Issue: 145(1), P. 119 - 141

Published: June 1, 2021

Abstract Cerebral palsy is the most prevalent physical disability in children; however, its inherent molecular mechanisms remain unclear. In present study, we performed in-depth clinical and analysis on 120 idiopathic cerebral families, identified underlying detrimental genetic variants 45% of these patients. addition to germline variants, found disease-related postzygotic mutations ∼6.7% We that patients with more severe motor impairments or a comorbidity intellectual had significantly higher chance harbouring variants. By compilation 114 known cerebral-palsy-related genes, characteristic features terms inheritance function, from which proposed dichotomous classification system according expression patterns genes associated cognitive impairments. two both disability, revealed defective TYW1, tRNA hypermodification enzyme, caused primary microcephaly problems motion cognition by hindering neuronal proliferation migration. Furthermore, developed an algorithm demonstrated mouse brains this malfunctioning specifically perturbed translation subset proteins involved cell cycling. This finding provided novel interesting mechanism for congenital microcephaly. another patient normal intelligence, mitochondrial enzyme GPAM, hypomorphic form led hypomyelination corticospinal tract human models. addition, confirmed aberrant Gpam mice lipid metabolism astrocytes, resulting suppressed astrocytic shortage contents supplied oligodendrocytic myelination. Taken together, our findings elucidate aspects aetiology provide insights future therapeutic strategies.

Language: Английский

Citations

64
How can same-gene mutations promote both cancer and developmental disorders? DOI Creative Commons
Ruth Nussinov, Chung‐Jung Tsai, Hyunbum Jang

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(2)

Published: Jan. 14, 2022

This review offers why same-gene mutations can lead to cancer and neurodevelopmental disorders a high risk of cancer.

Language: Английский

Citations

48
Development of a Bedside Tool to Predict the Diagnosis of Cerebral Palsy in Term-Born Neonates DOI

Amira Rouabhi,

Nafisa Husein,

Deborah Dewey

et al.

JAMA Pediatrics, Journal Year: 2023, Volume and Issue: 177(2), P. 177 - 177

Published: Jan. 17, 2023

Cerebral palsy (CP) is the most common abnormality of motor development and causes lifelong impairment. Early diagnosis therapy can improve outcomes, but early identification infants at risk remains challenging.

Language: Английский

Citations

24
Effect of individual variations in genes related to dopamine brain transmission on performance with and without rewards during motor sequence and probabilistic learning tasks in children and young adults with and without cerebral palsy DOI Creative Commons

Barrett Dryden,

Jesse Matsubara,

Eric M. Wassermann

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314173 - e0314173

Published: Jan. 9, 2025

Children with cerebral palsy (CP) often participate in training to improve mobility, hand function and other motor abilities. However, responses these interventions vary considerably across individuals even those similar brain injuries, ages functional levels. Dopamine is a neurotrasmitter known affect skill acquistion animals humans may be influenced by individual variations genes related transmission of dopamine. To evaluate potential genetic influences on learning young people without CP, we calculated dopamine-related gene scores compared the ability learn two different tasks, an implicit sequence task probablistic classification task. Each was also administered unrewarded condition rewarded one increase circulating levels The main finding interaction between score for such that low were poorer learners rewards but responded positively whereas converse true high scores. This first prospective study CP suggesting variability influence neurorehabilitation outcomes could potentially modulated using or medications at baseline, thus promoting more personalized approaches enhancing neurological conditions.

Language: Английский

Citations

1