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World Journal of Pediatrics : WJP Aug 2023Neurodevelopmental disorders are a heterogeneous group of conditions that manifest as delays or deviations in the acquisition of expected developmental milestones and... (Review)
Review
BACKGROUND
Neurodevelopmental disorders are a heterogeneous group of conditions that manifest as delays or deviations in the acquisition of expected developmental milestones and behavioral changes. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication and social interaction and by repetitive and restricted patterns of behavior, interests and activities. The aim of this review is to discuss the clinical features of the differential diagnoses of ASD that are prevalent among preschoolers, focusing on their similarities and disparities.
DATA SOURCES
The international medical literature search was conducted using PubMed and was revised regarding the subject using single and/or combined keywords as follows: differential diagnosis, preschoolers, diagnostic challenge, attention deficit hyperactivity disorder, intellectual disability, high abilities/giftedness, childhood apraxia of speech, social communication disorder, Landau-Kleffner syndrome, stereotyped movement disorder and excessive screen time.
RESULTS
We describe conditions commonly found in clinical practice, taking ASD as a reference. We addressed converging and divergent aspects of behavior, cognition, communication, language, speech, socialization, and stereotypes for the diagnosis of ASD and other disorders identified as potential differential or comorbid diagnoses.
CONCLUSIONS
The ranking and characterization of symptoms appear to be essential for better understanding the underlying common ground between children with developmental disorders and children with ASD, thus properly diagnosing and directing social, professional, or medication interventions. This detailed discussion adds to the literature since, although ASD differential diagnoses are frequently mentioned and discussed in textbooks and journal articles, they rarely occupy a prominent place as we aimed herein.
Topics: Child; Child, Preschool; Humans; Autism Spectrum Disorder; Diagnosis, Differential; Developmental Disabilities; Comorbidity; Cognition
PubMed: 36282408
DOI: 10.1007/s12519-022-00629-y -
Genes May 2024The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental... (Review)
Review
The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental disability, became the basis for phenotyping children with the features that became known as Mabry syndrome. Aside from improvements in the services available to patients and families, however, the diagnosis and treatment of this, and many other developmental disabilities, did not change significantly until the advent of massively parallel sequencing. As more patients with features of the Mabry syndrome were identified, exome and genome sequencing were used to identify the glycophosphatidylinositol (GPI) biosynthesis disorders (GPIBDs) as a group of congenital disorders of glycosylation (CDG). Biallelic variants of the phosphatidylinositol glycan (PIG) biosynthesis, type V () gene identified in Mabry syndrome became evidence of the first in a phenotypic series that is numbered HPMRS1-6 in the order of discovery. HPMRS1 [MIM: 239300] is the phenotype resulting from inheritance of biallelic variants. Similarly, HPMRS2 (MIM 614749), HPMRS5 (MIM 616025) and HPMRS6 (MIM 616809) result from disruption of the , and genes expressed in the endoplasmic reticulum. By contrast, HPMRS3 (MIM 614207) and HPMRS4 (MIM 615716) result from disruption of post attachment to proteins (HPMRS3) and (HPMRS4). The GPI biosynthesis disorders (GPIBDs) are currently numbered GPIBD1-21. Working with Dr. Mabry, in 2020, we were able to use improved laboratory diagnostics to complete the molecular diagnosis of patients he had originally described in 1970. We identified biallelic variants of the gene in the first reported HPMRS patients. We discuss the longevity of the Mabry syndrome index patients in the context of the utility of pyridoxine treatment of seizures and evidence for putative glycolipid storage in patients with HPMRS3. From the perspective of the laboratory innovations made that enabled the identification of the HPMRS phenotype in Dr. Mabry's patients, the need for treatment innovations that will benefit patients and families affected by developmental disabilities is clear.
Topics: Humans; Developmental Disabilities; Glycosylphosphatidylinositols; Congenital Disorders of Glycosylation; Phenotype; Male; Mutation; Female; Membrane Proteins; Mannosyltransferases
PubMed: 38790248
DOI: 10.3390/genes15050619 -
American Journal on Intellectual and... Sep 2023"Toward Equity in Research on Intellectual and Developmental Disabilities" (IDD) is a timely and comprehensive article highlighting gaps in the "dominant culture"...
"Toward Equity in Research on Intellectual and Developmental Disabilities" (IDD) is a timely and comprehensive article highlighting gaps in the "dominant culture" approach to current research strategies designed to address IDD. Recentering systems involved in the research enterprise are recommended. This commentary provides additional guidance from a social justice, equity, and inclusion lens, including a clinical anthropology approach to research.
Topics: Humans; Child; Developmental Disabilities; Research Design
PubMed: 37644859
DOI: 10.1352/1944-7558-128.5.371 -
Journal of Intellectual Disabilities :... Sep 2023Friendships contribute to positive social outcomes such as the promotion of prosocial behaviors and social well-being and can lead to an overall healthy quality of life....
Friendships contribute to positive social outcomes such as the promotion of prosocial behaviors and social well-being and can lead to an overall healthy quality of life. Despite the importance of friendships, little is known about how individuals without disabilities develop and maintain friendships with individuals with intellectual and developmental disabilities. Using a phenomenological research design, the current study explored the lived experiences of 17 adults without disabilities who discussed the development and maintenance of their friendship with an individual with intellectual and developmental disabilities. Semi-structured interviews were conducted and subsequently collaborative, open coding was used to identify codes and themes across participants. Three main themes emerged related to 1) factors that facilitated friendship development; 2) factors that contributed to friendship maintenance; and 3) impacts of the friendship for both individuals with and without intellectual and developmental disabilities. Implications of the results are discussed as well as future directions for research.
Topics: Child; Humans; Adult; Friends; Developmental Disabilities; Quality of Life; Intellectual Disability; Disabled Persons
PubMed: 35624542
DOI: 10.1177/17446295221104621 -
Journal of Neurodevelopmental Disorders Jun 2024Intellectual and developmental disabilities (IDDs) are associated with both cognitive challenges and difficulties in conceptual, social, and practical areas of living,...
BACKGROUND
Intellectual and developmental disabilities (IDDs) are associated with both cognitive challenges and difficulties in conceptual, social, and practical areas of living, commonly referred to as adaptive behavior (DSM-5). Although cross-sectional associations between intelligence or cognition and adaptive behavior have been reported in IDD populations, no study to date has examined whether developmental changes in cognition contribute to or track with changes in adaptive behavior. The present study sought to examine associations of longitudinal developmental change in domains of cognition (NIH Toolbox Cognition Battery, NIHTB-CB) and adaptive behavior domains (Vineland Adaptive Behavior Scales-3; VABS-3) including Socialization, Communication, and Daily Living Skills (DLS) over a two year period in a large sample of children, adolescents and young adults with IDD.
METHODS
Three groups were recruited, including those with fragile X syndrome, Down syndrome, and other/idiopathic intellectual disability. Eligible participants (n = 263) included those who were between 6 and 26 years (m = 15.52, sd = 5.17) at Visit 1, and who had a diagnosis of, or suspected intellectual disability (ID), including borderline ID, with a mental age of at least 3.0 years. Participants were given cognitive and adaptive behavior assessments at two time points over a two year period (m = 2.45 years, range = 1.27 to 5.56 years). In order to examine the association of developmental change between cognitive and adaptive behavior domains, bivariate latent change score (BLCS) models were fit to compare change in the three cognitive domains measured by the NIHTB-CB (Fluid Cognition, Crystallized Cognition, Total Cognition) and the three adaptive behavior domains measured by the VABS-3 (Communication, DLS, and Socialization).
RESULTS
Over a two year period, change in cognition (both Crystallized and Total Composites) was significantly and positively associated with change in daily living skills. Also, baseline cognition level predicted growth in adaptive behavior, however baseline adaptive behavior did not predict growth in cognition in any model.
CONCLUSIONS
The present study demonstrated that developmental changes in cognition and adaptive behavior are associated in children and young adults with IDD, indicating the potential for cross-domain effects of intervention. Notably, improvements in DLS emerged as a primary area of adaptive behavior that positively related to improvements in cognition. This work provides evidence for the clinical, "real life" meaningfulness of changes in cognition detected by the NIHTB-CB in IDD, and provides empirical support for the NIHTB-CB as a fit-for-purpose performance-based outcome measure for this population.
Topics: Humans; Male; Child; Adolescent; Female; Adaptation, Psychological; Young Adult; Adult; Intellectual Disability; Developmental Disabilities; Cognition; Longitudinal Studies; Activities of Daily Living; Socialization; Down Syndrome; Fragile X Syndrome
PubMed: 38872099
DOI: 10.1186/s11689-024-09542-z -
International Journal of Qualitative... Dec 2024For children with neurodevelopmental disabilities (CWNDs), early diagnosis that leads to early intervention with regular targeted therapies is critical. In Qatar,...
PURPOSE
For children with neurodevelopmental disabilities (CWNDs), early diagnosis that leads to early intervention with regular targeted therapies is critical. In Qatar, private therapy centres that address this demand often have highly exclusive prices restricting families from availing them. This paper examines the challenges faced by families with CWNDs, as well as various financial and systemic obstacles, from the vantage point of these centres, all of which culminate in an extraordinarily high disability price tag for disability families in Qatar.
METHODS
This study is based on qualitative, semi-structured, and in-depth interviews with private therapy centres and developmental paediatricians.
RESULTS
Therapy centre representatives expressed common struggles in lengthy and cumbersome administration and licencing procedures, difficulty in hiring and retaining high quality staff, and expenses that need to be paid to the state. From their experience, families largely struggle with delayed diagnoses that significantly slow down intervention plans and therapies as well as staggeringly high financial costs with a dearth of funding options.
CONCLUSIONS
We recommend sincere engagement, dialogue, and cooperation between multiple stakeholders; a supportive ecosystem to balance and distribute the demand that includes schools and parents; as well more efficient administrative procedures and recruitment strategies.
Topics: Humans; Child; Qatar; Developmental Disabilities; Disabled Children; Qualitative Research; Male; Female; Parents; Child, Preschool; Early Diagnosis; Neurodevelopmental Disorders
PubMed: 38657277
DOI: 10.1080/17482631.2024.2345816 -
Journal of Medical Genetics Nov 2023Helios (encoded by ), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although...
Dominant negative variants in cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.
BACKGROUND
Helios (encoded by ), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4 regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.
METHODS
We performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation combined with syndromic features including craniofacial differences, sensorineural hearing loss and congenital abnormalities.
RESULTS
Genome sequencing revealed heterozygous variants that alter the critical DNA-binding zinc fingers (ZFs) of Helios. Proband 1 had a tandem duplication of ZFs 2 and 3 in the DNA-binding domain of Helios (p.Gly136_Ser191dup) and Proband 2 had a missense variant impacting one of the key residues for specific base recognition and DNA interaction in ZF2 of Helios (p.Gly153Arg). Functional studies confirmed that both these variant proteins are expressed and that they interfere with the ability of the wild-type Helios protein to perform its canonical function-repressing transcription activity-in a dominant negative manner.
CONCLUSION
This study is the first to describe dominant negative variants. These variants cause a novel genetic syndrome characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay.
Topics: Humans; DNA-Binding Proteins; Hearing Loss; Ikaros Transcription Factor; Syndrome; Developmental Disabilities; Craniofacial Abnormalities
PubMed: 37316189
DOI: 10.1136/jmg-2022-109127 -
American Journal of Medical Genetics.... Aug 2023SRRM2-related neurodevelopmental disorder is a recently described genetic diagnosis caused by loss-of-function variants in SRRM2. In order to understand the clinical...
SRRM2-related neurodevelopmental disorder is a recently described genetic diagnosis caused by loss-of-function variants in SRRM2. In order to understand the clinical spectrum of SRRM2-related neurodevelopmental disorder, we performed a retrospective exome data and clinical chart review at a single tertiary children's hospital, Children's Hospital of Philadelphia (CHOP). Among approximately 3100 clinical exome sequencing cases performed at CHOP, we identified three patients with SRRM2 loss-of-function pathogenic variants, in addition to one patient previously described in the literature. Common clinical features include developmental delay, attention deficit hyperactivity disorder, macrocephaly, hypotonia, gastroesophageal reflux, overweight/obesity, and autism. While developmental disabilities are commonly seen in all individuals with SRRM2 variants, the degree of developmental delay and intellectual disability is variable. Our data suggest that SRRM2-related neurodevelopmental disorder can be identified in 0.3% of individuals with developmental disabilities receiving exome sequencing.
Topics: Humans; Child; Developmental Disabilities; Retrospective Studies; Neurodevelopmental Disorders; Intellectual Disability; Hospitals; RNA-Binding Proteins
PubMed: 37212523
DOI: 10.1002/ajmg.a.63302 -
American Journal on Intellectual and... Mar 2024Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment,...
Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.
Topics: Child; Humans; Adolescent; Motivation; Goals; Developmental Disabilities; Parents; Employment; Intellectual Disability
PubMed: 38411244
DOI: 10.1352/1944-7558-129.2.151 -
Intellectual and Developmental... Aug 2023Medicaid Home- and Community-Based Services (HCBS) 1915(c) waivers are the most prominent funding mechanism for the long-term services and supports (LTSS) of people with...
Medicaid Home- and Community-Based Services (HCBS) 1915(c) waivers are the most prominent funding mechanism for the long-term services and supports (LTSS) of people with intellectual and developmental disabilities (IDD). This study's aim was to conduct an in-depth national analysis of fiscal year (FY) 2021 HCBS 1915(c) waivers for people with IDD. In FY 2021, over $43.2 billion was projected for the HCBS of 861,038 people with IDD. An average of $47,315 was projected per person with IDD annually. The services that received the most funding were: residential habilitation; supports to live in one's own home; and day habilitation. HCBS is necessary so people with IDD can live and thrive in their communities.
Topics: United States; Child; Humans; Community Health Services; Home Care Services; Medicaid; Developmental Disabilities; Intellectual Disability; Long-Term Care
PubMed: 37536690
DOI: 10.1352/1934-9556-61.4.269