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Experimental & Molecular Medicine Mar 2021Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic... (Review)
Review
Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic compound screenings, and other biomedical research applications. With the impactful developments of CRISPR and next-generation sequencing technology, disease modeling in zebrafish is accelerating the understanding of the molecular mechanisms of human genetic diseases. These efforts are fundamental for the future of precision medicine because they provide new diagnostic and therapeutic solutions. This review focuses on zebrafish disease models for biomedical research, mainly in developmental disorders, mental disorders, and metabolic diseases.
Topics: Animals; Biomedical Research; Developmental Disabilities; Disease Models, Animal; Humans; Mental Disorders; Metabolic Diseases; Zebrafish
PubMed: 33649498
DOI: 10.1038/s12276-021-00571-5 -
American Journal of Medical Genetics.... Sep 2015Disorders resulting from 5p deletions (5p-) were first recognized by Lejeune et al. in 1963 [Lejeune et al. (1963); C R Hebd Seances Acad Sci 257:3098-3102]. 5p- is... (Review)
Review
Disorders resulting from 5p deletions (5p-) were first recognized by Lejeune et al. in 1963 [Lejeune et al. (1963); C R Hebd Seances Acad Sci 257:3098-3102]. 5p- is caused by partial or total deletion of the short arm of chromosome 5. The most recognizable phenotype is characterized by a high-pitched cry, dysmorphic features, poor growth, and developmental delay. This report reviews 5p- disorders and their molecular basis. Hemizygosity for genes located within this region have been implicated in contributing to the phenotype. A review of the genes on 5p which may be dosage sensitive is summarized. Because of the growing knowledge of these specific genes, future directions to explore potential targeted therapies for individuals with 5p- are discussed. © 2015 Wiley Periodicals, Inc.
Topics: Chromosome Deletion; Chromosomes, Human, Pair 5; Developmental Disabilities; Humans; Phenotype
PubMed: 26235846
DOI: 10.1002/ajmg.c.31444 -
Pediatric Clinics of North America Jun 1993A large number of infants are born each year with biologic or environmental risk factors that put them at increased risk for developmental disability, although most do... (Review)
Review
A large number of infants are born each year with biologic or environmental risk factors that put them at increased risk for developmental disability, although most do not go on to have major disabilities. Some risk factors, for example, intraparenchymal hemorrhage, periventricular cysts, encephalomalacia, and abnormal neurodevelopmental examination, carry a much higher risk of developmental disability than others. There is much overlap among risk factors, and infants with multiple risk factors generally have a greater risk of disability than infants with just a single risk factor. All high-risk infants should receive careful pediatric follow-up that includes developmental screening, but efficient use of so far quite limited resources argues for selection of the highest risk infants for comprehensive developmental follow-up or early intervention programs. A system of tracking and monitoring high-risk infants during infancy and childhood would allow for early identification of developmental delay and appropriate referral for community resources.
Topics: Child, Preschool; Developmental Disabilities; Disabled Persons; Humans; Infant; Risk Factors
PubMed: 7684121
DOI: 10.1016/s0031-3955(16)38545-5 -
Current Opinion in Neurology Apr 2015The heterogeneity in clinical presentation and outcome in neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) autism spectrum disorder... (Review)
Review
PURPOSE OF REVIEW
The heterogeneity in clinical presentation and outcome in neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) autism spectrum disorder (ASD) necessitates the identification and validation of biomarkers that can guide diagnosis, predict developmental outcomes, and monitor treatment response. Electrophysiology holds both practical and theoretical advantages as a clinical biomarker in neurodevelopmental disorders, and considerable effort has been invested in the search for electroencephalography (EEG) biomarkers in ADHD and ASD.
RECENT FINDINGS
Here, we discuss the major themes in the evaluation of biomarkers and then review studies that have applied EEG to better inform diagnosis, focusing on the controversy surrounding the theta:beta ratio in ADHD; prediction of risk, highlighting recent studies of infants at high risk for ASD; and treatment monitoring, presenting new efforts in the redefinition of outcome measures in clinical trials of ASD treatment.
SUMMARY
We conclude that insights gained from EEG studies will contribute significantly to a more mechanistic understanding of these disorders and to the development of biomarkers that can assist with diagnosis, prognosis, and intervention. There is a need, however, to utilize approaches that accommodate, rather than ignore, diagnostic heterogeneity and individual differences.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Biomarkers; Child Development Disorders, Pervasive; Developmental Disabilities; Electroencephalography; Humans; Treatment Outcome
PubMed: 25710286
DOI: 10.1097/WCO.0000000000000181 -
Developmental Medicine and Child... Feb 2022To summarize developmental delay among infants and toddlers with sickle cell disease (SCD).
AIM
To summarize developmental delay among infants and toddlers with sickle cell disease (SCD).
METHOD
This systematic review included studies that reported developmental outcomes of children with SCD between 0 months and 48 months of age and followed standards set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Ten studies were included, describing 596 unique developmental assessments. The rate of developmental delay ranged from 17.5% to 50% and increased with age. Cognition was the only domain included in all studies and the most frequently identified delay. One study reported that more severe SCD genotypes predicted worse development, while five studies reported no difference in rates of developmental delay across genotypes.
INTERPRETATION
These findings emphasize the need for standardized screening to identify children with SCD at risk of delay at a young age to facilitate appropriate referrals for therapeutic intervention. Frequent and comprehensive developmental screening is necessary among all SCD genotypes.
Topics: Anemia, Sickle Cell; Child, Preschool; Developmental Disabilities; Humans; Infant; Infant, Newborn
PubMed: 34535892
DOI: 10.1111/dmcn.15048 -
Pediatric Clinics of North America Oct 2013Children with mental health problems are increasingly being evaluated and treated by both pediatric primary care and pediatric emergency physicians. This article focuses... (Review)
Review
Children with mental health problems are increasingly being evaluated and treated by both pediatric primary care and pediatric emergency physicians. This article focuses on the epidemiology, evaluation, and management of the 2 most common pediatric mental health emergencies, suicidal and homicidal/aggressive patients, as well as the equally challenging population of children with autism or other developmental disabilities.
Topics: Autistic Disorder; Child; Developmental Disabilities; Emergency Services, Psychiatric; Health Services Needs and Demand; Humans; Mental Disorders; Risk Factors; Suicide
PubMed: 24093903
DOI: 10.1016/j.pcl.2013.06.006 -
Current Biology : CB Apr 2020Childhood learning difficulties and developmental disorders are common, but progress toward understanding their underlying brain mechanisms has been slow. Structural...
Childhood learning difficulties and developmental disorders are common, but progress toward understanding their underlying brain mechanisms has been slow. Structural neuroimaging, cognitive, and learning data were collected from 479 children (299 boys, ranging in age from 62 to 223 months), 337 of whom had been referred to the study on the basis of learning-related cognitive problems. Machine learning identified different cognitive profiles within the sample, and hold-out cross-validation showed that these profiles were significantly associated with children's learning ability. The same machine learning approach was applied to cortical morphology data to identify different brain profiles. Hold-out cross-validation demonstrated that these were significantly associated with children's cognitive profiles. Crucially, these mappings were not one-to-one. The same neural profile could be associated with different cognitive impairments across different children. One possibility is that the organization of some children's brains is less susceptible to local deficits. This was tested by using diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child's connectome revealed that some brain networks were strongly organized around highly connected hubs. Children with these networks had only selective cognitive impairments or no cognitive impairments at all. By contrast, the same attacks had a significantly different impact on some children's networks, because their brain efficiency was less critically dependent on hubs. These children had the most widespread and severe cognitive impairments. On this basis, we propose a new framework in which the nature and mechanisms of brain-to-cognition relationships are moderated by the organizational context of the overall network.
Topics: Adolescent; Brain Mapping; Child; Child, Preschool; Cognition; Developmental Disabilities; England; Female; Humans; Learning; Male
PubMed: 32109389
DOI: 10.1016/j.cub.2020.01.078 -
Annals of Epidemiology Apr 2016Although previous studies demonstrate associations between adverse perinatal outcomes and developmental disabilities (DDs), study of population impacts is limited.
PURPOSE
Although previous studies demonstrate associations between adverse perinatal outcomes and developmental disabilities (DDs), study of population impacts is limited.
METHODS
We computed relative risks adjusted (aRRs) for sociodemographic factors and component and summary population attributable fractions (PAFs) for associations between very low birth weight (VLBW, all preterm births), moderately low birth weight (MLBW) + Preterm, MLBW at term, and normal birth weight (NBW) + Preterm and seven DDs (cerebral palsy [CP], autism spectrum disorder [ASD], intellectual disability [ID], behavioral-conduct disorders, attention-deficit-hyperactivity disorder [ADHD], learning disability [LD], and other developmental delay) among children aged 3-17 years in the 2011-2012 National Survey of Children's Health.
RESULTS
VLBW-Preterm, MLBW-Preterm and NBW-Preterm were strongly to moderately associated with CP (aRRs: 43.5, 10.1, and 2.2, respectively; all significant) and also associated with ID, ASD, LD, and other developmental delay (aRR ranges: VLBW-Preterm 2.8-5.3; MLBW-Preterm 1.9-2.8; and NBW-Preterm 1.6-2.3). Summary PAFs for preterm birth and/or LBW were 55% for CP, 10%-20% for ASD, ID, LD, and other developmental delay, and less than 5% for ADHD and behavioral-conduct disorders. Findings were similar whether we assessed DDs as independent outcomes or within mutually exclusive categories accounting for DD co-occurrence.
CONCLUSIONS
Preterm birth has a sizable impact on child neurodevelopment. However, relative associations and population impacts vary widely by DD type.
Topics: Adolescent; Birth Weight; Child; Child, Preschool; Developmental Disabilities; Female; Follow-Up Studies; Gestational Age; Humans; Incidence; Infant, Low Birth Weight; Male; Maternal Age; Population Surveillance; Pregnancy; Premature Birth; Risk Factors; Socioeconomic Factors
PubMed: 27085382
DOI: 10.1016/j.annepidem.2016.02.012 -
Current Opinion in Neurobiology Oct 2012The genetic basis of neurodevelopmental and neuropsychiatric diseases has been advanced by the discovery of large and recurrent copy number variants significantly... (Review)
Review
The genetic basis of neurodevelopmental and neuropsychiatric diseases has been advanced by the discovery of large and recurrent copy number variants significantly enriched in cases when compared to controls. The pattern of this variation strongly implies that rare variants contribute significantly to neurological disease; that different genes will be responsible for similar diseases in different families; and that the same 'primary' genetic lesions can result in a different disease outcome depending potentially on the genetic background. Next-generation sequencing technologies are beginning to broaden the spectrum of disease-causing variation and provide specificity by pinpointing both genes and pathways for future diagnostics and therapeutics.
Topics: Animals; Developmental Disabilities; Genetic Predisposition to Disease; Genetic Variation; Humans; Models, Genetic; Nervous System Diseases
PubMed: 22560351
DOI: 10.1016/j.conb.2012.04.007 -
Developmental Medicine and Child... Dec 2012Low- and middle-income countries are experiencing a significant reduction in mortality of children under 5 years of age. This reduction is bringing in its wake large... (Review)
Review
Low- and middle-income countries are experiencing a significant reduction in mortality of children under 5 years of age. This reduction is bringing in its wake large numbers of surviving children with developmental delays and disabilities. Very little attention has been paid to these children, most of whom receive minimal or no support. Thus, there is an urgent need to recognize that improving the quality of life of the survivors must complement mortality reduction in healthcare practice and programs. The incorporation of early evaluation and intervention programs into routine pediatric care is likely to have the most impact on the quality of life of these children. We therefore call for leadership from practitioners, governments, and international organizations to prioritize regular childhood developmental surveillance for possible delays and disabilities, and to pursue early referral for intervention.
Topics: Child; Child Health Services; Cross-Cultural Comparison; Developmental Disabilities; Early Diagnosis; Humans; Quality of Life
PubMed: 22803576
DOI: 10.1111/j.1469-8749.2012.04348.x