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Genes Jun 2024This study delves into the diagnostic yield of whole-exome sequencing (WES) in pediatric patients presenting with developmental delay/intellectual disability (DD/ID),...
This study delves into the diagnostic yield of whole-exome sequencing (WES) in pediatric patients presenting with developmental delay/intellectual disability (DD/ID), while also exploring the utility of Reverse Phenotyping (RP) in refining diagnoses. A cohort of 100 pediatric patients underwent WES, yielding a diagnosis in 66% of cases. Notably, RP played a significant role in cases with negative prior genetic testing, underscoring its significance in complex diagnostic scenarios. The study revealed a spectrum of genetic conditions contributing to DD/ID, illustrating the heterogeneity of etiological factors. Despite challenges, WES demonstrated effectiveness, particularly in cases with metabolic abnormalities. Reverse phenotyping was indicated in half of the patients with positive WES findings. Neural network models exhibited moderate-to-exceptional predictive abilities for aiding in patient selection for WES and RP. These findings emphasize the importance of employing comprehensive genetic approaches and RP in unraveling the genetic underpinnings of DD/ID, thereby facilitating personalized management and genetic counseling for affected individuals and families. This research contributes insights into the genetic landscape of DD/ID, enhancing our understanding and guiding clinical practice in this particular field of clinical genetics.
Topics: Humans; Exome Sequencing; Developmental Disabilities; Child; Male; Intellectual Disability; Female; Child, Preschool; Phenotype; Infant; Adolescent; Genetic Testing
PubMed: 38927725
DOI: 10.3390/genes15060789 -
Genes May 2024Genetic counseling and treatment options for rare developmental disabilities (DDs) have been revolutionized by the opportunities made possible by using massively...
Genetic counseling and treatment options for rare developmental disabilities (DDs) have been revolutionized by the opportunities made possible by using massively parallel sequencing for diagnostic purposes [...].
Topics: Humans; Rare Diseases; Genetic Counseling; Phenotype; High-Throughput Nucleotide Sequencing; Genetic Testing; Developmental Disabilities
PubMed: 38927651
DOI: 10.3390/genes15060715 -
Genes May 2024To date, only 13 studies have described patients with large overlapping deletions of 10p11.2-p12. These individuals shared a common phenotype characterized by...
To date, only 13 studies have described patients with large overlapping deletions of 10p11.2-p12. These individuals shared a common phenotype characterized by intellectual disability, developmental delay, distinct facial dysmorphic features, abnormal behaviour, visual impairment, cardiac malformation, and cryptorchidism in males. Molecular cytogenetic analysis revealed that the deletion in this chromosomal region shares a common smallest region of overlap (SRO) of 80 kb, which contains only the gene (WW-domain-containing adaptor with coiled coil). In this clinical case report, we report a 5-year-old girl, born from non-consanguineous parents, with a 10p11.22p11.21 microdeletion. She presents clinical features that overlap with other patients described in the literature, such as dysmorphic traits, speech delay, and behavioural abnormalities (hyperactivity), even though the gene is not involved in the microdeletion. Our results are the first to highlight that the deletion described here represents a contiguous gene syndrome that is enough to explain the distinct phenotype but partially overlaps with the previous cases reported in the literature, even though the same genes are not involved. In particular, in this study, we speculate about the role of the gene that seems to be associated with normal motor development. In fact, we found that our patient is the only one described in the literature with a large deletion in the 10p11.22p11.21 region without the involvement of the gene deletion, and, interestingly, the patient did not have motor delay.
Topics: Humans; Female; Child, Preschool; Chromosome Deletion; Intellectual Disability; Abnormalities, Multiple; Syndrome; Phenotype; Developmental Disabilities
PubMed: 38927586
DOI: 10.3390/genes15060650 -
BMC Public Health Jun 2024People with serious mental illness (SMI) and people with intellectual disabilities/developmental disabilities (ID/DD) are at higher risk for COVID-19 and more severe... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
People with serious mental illness (SMI) and people with intellectual disabilities/developmental disabilities (ID/DD) are at higher risk for COVID-19 and more severe outcomes. We compare a tailored versus general best practice COVID-19 prevention program in group homes (GHs) for people with SMI or ID/DD in Massachusetts (MA).
METHODS
A hybrid effectiveness-implementation cluster randomized control trial compared a four-component implementation strategy (Tailored Best Practices: TBP) to dissemination of standard prevention guidelines (General Best-Practices: GBP) in GHs across six MA behavioral health agencies. GBP consisted of standard best practices for preventing COVID-19. TBP included GBP plus four components including: (1) trusted-messenger peer testimonials on benefits of vaccination; (2) motivational interviewing; (3) interactive education on preventive practices; and (4) fidelity feedback dashboards for GHs. Primary implementation outcomes were full COVID-19 vaccination rates (baseline: 1/1/2021-3/31/2021) and fidelity scores (baseline: 5/1/21-7/30/21), at 3-month intervals to 15-month follow-up until October 2022. The primary effectiveness outcome was COVID-19 infection (baseline: 1/1/2021-3/31/2021), measured every 3 months to 15-month follow-up. Cumulative incidence of vaccinations were estimated using Kaplan-Meier curves. Cox frailty models evaluate differences in vaccination uptake and secondary outcomes. Linear mixed models (LMMs) and Poisson generalized linear mixed models (GLMMs) were used to evaluate differences in fidelity scores and incidence of COVID-19 infections.
RESULTS
GHs (n=415) were randomized to TBP (n=208) and GBP (n=207) including 3,836 residents (1,041 ID/DD; 2,795 SMI) and 5,538 staff. No differences were found in fidelity scores or COVID-19 incidence rates between TBP and GBP, however TBP had greater acceptability, appropriateness, and feasibility. No overall differences in vaccination rates were found between TBP and GBP. However, among unvaccinated group home residents with mental disabilities, non-White residents achieved full vaccination status at double the rate for TBP (28.6%) compared to GBP (14.4%) at 15 months. Additionally, the impact of TBP on vaccine uptake was over two-times greater for non-White residents compared to non-Hispanic White residents (ratio of HR for TBP between non-White and non-Hispanic White: 2.28, p = 0.03).
CONCLUSION
Tailored COVID-19 prevention strategies are beneficial as a feasible and acceptable implementation strategy with the potential to reduce disparities in vaccine acceptance among the subgroup of non-White individuals with mental disabilities.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04726371, 27/01/2021. https://clinicaltrials.gov/study/NCT04726371 .
Topics: Humans; COVID-19; Male; Female; Adult; Massachusetts; Middle Aged; Group Homes; Mental Disorders; COVID-19 Vaccines; Intellectual Disability
PubMed: 38926810
DOI: 10.1186/s12889-024-18835-w -
BMC Pediatrics Jun 2024The main cause of growth and development delays remains unknown, but it can occur as an interaction between genetic, environmental, and socio-economic factors.
BACKGROUND
The main cause of growth and development delays remains unknown, but it can occur as an interaction between genetic, environmental, and socio-economic factors.
OBJECTIVE
The aim of the study was to investigate the prevalence and social determinants of growth and developmental delays among children aged under five years in Qazvin, Iran.
METHODS
A cross-sectional study was conducted between January 2019 to December 2020 with participation of 1800 mothers with children aged 4-60 months who were referred to comprehensive health centers in Qazvin city, Iran. Structural and intermediate social determinants of health were assessed including: parents and children socio-demographic characteristics, families' living and economic status, parents' behavioral factors, household food security, mother's general health, and perceived social support. Children's growth was assessed based on their anthropometric assessment and their development was assessed using their age-specific Ages and Stages Questionnaire. Data were analyzed using univariable and multivariable logistic regression models using SPSS software version 24 and Stata version 14.
RESULTS
The prevalence of developmental problems in each domain were 4.28% for personal and social delay, 5.72% for gross motor delay, 6.5% for communication delay, 6.72% for fine motor delay, and 8% for problem-solving delay. The prevalence of weight growth delays was 13.56% and height growth delays was 4.66%. Communication, gross motor, and problem-solving delays were higher among children whose fathers' smoked cigarettes. Fine motor delays were lower among mothers with education status of high school diploma and university degree vs. the under diploma group. Personal and social delay was significantly higher among families with fair economic status and lower among children when their fathers were employed (vs. unemployed). Weight and height growth delays were higher among mothers who had experienced pregnancy complications and household food insecure families, respectively.
CONCLUSION
There are different predictors of growth and developmental delay problems among Iranian children aged under five years including fathers' smoking, families' economic status, and household food insecurity as well as history of mothers' pregnancy complications. The present study's findings can be used to screen for at-risk of growth and developmental delays among children and could help in designing and implementation of timely interventions.
Topics: Humans; Cross-Sectional Studies; Iran; Developmental Disabilities; Child, Preschool; Female; Prevalence; Infant; Male; Growth Disorders; Socioeconomic Factors; Social Determinants of Health; Child Development
PubMed: 38926691
DOI: 10.1186/s12887-024-04880-2 -
BMJ Paediatrics Open Jun 2024Early identification of suspected developmental delays (SDDs) is crucial for planning early interventions. This study aimed to determine the prevalence of SDDs and the...
BACKGROUND
Early identification of suspected developmental delays (SDDs) is crucial for planning early interventions. This study aimed to determine the prevalence of SDDs and the associated determinants in children aged 12 months in the northeast of Iran, using the Age and Stage Questionnaire-3 (ASQ-3) as the evaluative tool.
METHODS
This study conducted an analytical cross-sectional design to investigate all children who had completed the ASQ-3 screening form at 12 months of age within the time frame of 2016-2023 in the northeast of Iran. The necessary data were extracted from the electronic health record database associated with Mashhad University of Medical Sciences. To examine the factors associated with SDDs within each domain of the ASQ-3, a multiple logistic regression model was employed, and the results were presented using ORs along with 95% CIs.
RESULTS
Over 7 years, 236 476 children (96.74%) underwent routine ASQ-3 screening at 12 months. After excluding certain cases, 226 076 children (95.60%) were included. Among them, 51 593 children (22.82%) had a score below -1 SD, indicating SDD prevalence in at least one domain. The social-personal domain had the highest prevalence with 22 980 children (10.16%), while the gross motor domain had the lowest with 5650 children (2.50%). Logistic regression analysis identified strong predictors of SDDs, including hospitalisation at birth (OR=1.85, 95% CI:1.69 to 2.02), prematurity (OR=1.56, 95% CI: 1.37 to 1.79), urbanisation (OR=1.51, 95% CI: 1.45 to 1.57), boys (OR=1.36, 95% CI: 1.31 to 1.40) and lack of exclusive breast feeding until 6 months (OR=1.30, 95% CI: 1.25 to 1.34).
CONCLUSION
The prevalence of SDDs highlights the urgency for prompt action, while considering contributing factors. Policymakers can address modifiable risk factors associated with SDDs, including urbanisation risks, support programmes for immigrant families and the importance of exclusive breast feeding until 6 months. Additionally, it is recommended establishing gender-specific local standard cut-off points for the ASQ.
Topics: Humans; Iran; Developmental Disabilities; Male; Female; Cross-Sectional Studies; Prevalence; Infant; Risk Factors; Surveys and Questionnaires; Logistic Models
PubMed: 38925677
DOI: 10.1136/bmjpo-2023-002393 -
Diabetic Medicine : a Journal of the... Jun 2024Adults with intellectual and developmental disabilities (IDD) have a significantly higher prevalence of Type 2 diabetes than the general population. Evidence that...
AIM
Adults with intellectual and developmental disabilities (IDD) have a significantly higher prevalence of Type 2 diabetes than the general population. Evidence that lifestyle and/or behavioural interventions, such as participation in Special Olympics, decreases the risk of developing diabetes in adults with IDD could help minimize health disparities and promote overall health in this population.
METHODS
This was a 20-year retrospective cohort study of adults with IDD (30-39 years) in the province of Ontario, Canada, that compared hazard rates of diabetes among Special Olympics participants (n = 4145) to non-participants (n = 31,009) using administrative health databases housed at ICES. Using cox proportional hazard models, crude and adjusted hazard ratios were calculated for the association between the primary independent variable (Special Olympics participation status) and the dependent variable (incident diabetes cases).
RESULTS
After controlling for other variables, the hazard ratio comparing rates for developing diabetes between Special Olympics participants and non-participants was 0.85. This represents a 15% reduction in the hazard among Special Olympics participants when followed for up to 20 years. This result was statistically significant and represents a small effect size.
CONCLUSIONS
Special Olympics could be considered a complex intervention that promotes physical activity engagement through sport participation, health screenings, and the promotion of healthy eating habits through educational initiatives. This study provides evidence that Special Olympics participation decreases the rate for developing diabetes.
PubMed: 38925549
DOI: 10.1111/dme.15393 -
Pediatric Neurology Jun 2024Pontocerebellar hypoplasia type 10 (PCH10) due to CLP1 gene mutations is characterized by structural brain anomalies, progressive microcephaly, severe intellectual and...
BACKGROUND
Pontocerebellar hypoplasia type 10 (PCH10) due to CLP1 gene mutations is characterized by structural brain anomalies, progressive microcephaly, severe intellectual and physical disabilities, and spasticity. In this follow-up study, evolution of phenotypic and neurological characteristics of patients with PCH10 is discussed.
METHODS
Phenotype, growth parameters, motor functions, developmental tests, spasticity assessments, functional independence assessments, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) of 10 patients with PCH10 were monitored on separate examinations. Alterations were recorded.
RESULTS
Patients were followed-up for an average of 2.83 years. The tone of the upper extremities was significantly higher than that of the lower extremities, according to Modified Ashworth Scale (MAS) values. Sixty percent of patients could sit unsupported; 20% achieved supported sitting initially but lost the ability during follow-up. Absence of grabbing or sitting was observed in 20% of patients. During follow-up, one person achieved supported sitting and one person achieved head holding. Only one patient was able to speak a few words. Cerebellar atrophy (two of 10), pons hypoplasia (four of 10), cortical atrophy (seven of 10), enlarged ventricles (10 of 10), thinning of the corpus callosum (10 of 10), hypomyelination (six of 10), and increased white matter signal intensity (six of 10) were the observed MRI findings.
CONCLUSIONS
Progressive cerebral and cerebellar atrophy was demonstrated radiologically for the first time in a PCH10 cohort. It is of crucial importance to identify these patients promptly with the help of dysmorphic findings and spasticity being pronounced in the upper extremities. Furthermore, we note that phenotypic and neurological examination findings tend to change slightly over time.
PubMed: 38925092
DOI: 10.1016/j.pediatrneurol.2024.05.017 -
Pediatric Reports May 2024Neither radiological phenotypic characteristics nor reconstruction CT scan has been used to study the early anatomical disruption of the cranial bone in children with...
BACKGROUND
Neither radiological phenotypic characteristics nor reconstruction CT scan has been used to study the early anatomical disruption of the cranial bone in children with the so-called idiopathic type of West syndrome.
MATERIAL AND METHODS
The basic diagnostic measures and the classical antiepileptic treatments were applied to these children in accordance with the conventional protocol of investigations and treatment for children with West syndrome. Boys from three unrelated families were given the diagnosis of the idiopathic type of West syndrome, aged 7, 10 and 12 years old. Parents underwent extensive clinical examinations. Three parents (age range of 28-41 year) were included in this study. All children showed a history of intellectual disabilities, cryptogenic epileptic spasms and fragmented hypsarrhythmia. These children and their parents were referred to our orthopedic departments because of variable skeletal deformities. Variable forms of skeletal deformities were the motive for the families to seek orthopedic advice. A constellation of flat foot, torticollis and early-onset osteoarthritis were observed by the family doctor. Apparently, and from the first clinical session in our practice, we felt that all these children are manifesting variable forms of abnormal craniofacial contour. Thereby, we immediately performed detailed cranial radiological phenotypic characterization of every affected child, as well as the siblings and parents, and all were enrolled in this study. All affected children underwent whole-exome sequence analysis.
RESULTS
The craniofacial phenotype of all children revealed apparent developmental anatomical disruption of the cranial bones. Palpation of the skull bones showed unusual palpable bony ridges along different sutural locations. A 7-year-old child showed abnormal bulging over the sagittal suture, associated with bilateral bony ridges over the squamosal sutures. AP skull radiograph of a 7-year-old boy with West syndrome showed facial asymmetry with early closure of the metopic suture, and other sutures seemed ill-defined. A 3D reconstruction CT scan of the skull showed early closure of the metopic suture. Another 3D reconstruction CT scan of the skull while the patient was in flexion showed early closure of the squamosal sutures, pressing the brain contents upward, causing the development of a prominent bulge at the top of the mid-sagittal suture. A reformatted 3D reconstruction CT scan confirmed the bilateral closure of the squamosal suture. Examination of the parents revealed a similar skull radiographic abnormality in his mother. A 3D reformatted frontal cranial CT of a 35-year-old mother showed early closure of the metopic and sagittal sutures, causing a mid-sagittal bony bulge. A 10-year-old boy showed an extremely narrow frontal area, facial asymmetry and a well palpable ridge over the lambdoid sutures. A 3D axial reconstruction CT scan of a 10-year-old boy with West syndrome illustrated the asymmetry of the posterior cranial bones along the lambdoid sutures. Interestingly, his 28-year-old mother has been a client at the department of spine surgery since she was 14 years old. A 3D reconstruction CT scan of the mother showed a noticeable bony ridge extending from the metopic suture upwards to involve the sagittal suture (red arrow heads). The black arrow shows a well demarcated bony ridge over the squamosal suture. A 3D reconstruction CT scan of the skull and spine showed the thick bony ridge of the metopic and the anterior sagittal as well as bilateral involvement of the squamosal, causing apparent anterior narrowing of the craniofacial contour. Note the lumbar scoliosis. A 12-year-old boy showed brachycephaly. A lateral skull radiograph of a 12-year-old boy with West syndrome showed premature sutural fusion, begetting an abnormal growth pattern, resulting in cranial deformity. The nature of the deformity depends on which sutures are involved, the time of onset and the sequence in which individual sutures fuse. In this child, brachycephalic secondary to craniosynostosis, which occurred because of bilateral early ossification of the coronal sutures, led to bi-coronal craniosynostosis. Thickened frontal bones and an ossified interclinoid ligament of the sella turcica were encountered. The lateral skull radiograph of a 38-year-old mother with a history of poor schooling achievements showed a very similar cranial contour of brachycephaly, thickening of the frontal bones and massive ossification of the clinoid ligament of the sella turcica. Maternal history revealed a history of multiple spontaneous miscarriages in the first trimester of more than five times. Investigating his parents revealed a brachycephalic mother with borderline intelligence. We affirm that the pattern of inheritance in the three boys was compatible with the X-linked recessive pattern of inheritance. Whole-exome sequencing showed non-definite phenotype/genotype correlation.
CONCLUSIONS
The aim of this study was sixfold: firstly, to refute the common usage of the term idiopathic; secondly, we feel that it could be possible that West syndrome is a symptom complex rather than a separate diagnostic entity; thirdly, to further detect the genetic carrier, we explored the connection between the cranial bones in children with West syndrome with what has been clinically observed in their parents; fourthly, the early life anatomical disruptions of the cranial bones among these children seem to be heterogeneous; fifthly, it shows that the progressive deceleration in the development of this group of children is highly connected to the progressive closure of the cranial sutures; sixthly, we affirm that our findings are novel.
PubMed: 38921700
DOI: 10.3390/pediatric16020035 -
Healthcare (Basel, Switzerland) Jun 2024(1) Background: Auditory processing (AP) disorder is associated with learning difficulties and poses challenges to school-aged children in their daily activities. This... (Review)
Review
(1) Background: Auditory processing (AP) disorder is associated with learning difficulties and poses challenges to school-aged children in their daily activities. This scoping review identifies interventions and provides audiologists with protocol insights and outcome measures. (2) Methods: A systematic search of both peer-reviewed and grey literature (January 2006 to August 2023) covered ten databases. Studies included had the following characteristics: (i) published in French or English; (ii) participants were school-aged, and had a normal audiogram, AP difficulties or disorder, and no cognitive, developmental, congenital or neurological disorder (with the exception of learning, attention, and language disabilities); (iii) were intervention studies or systematic reviews. (3) Results: Forty-two studies were included, and they predominantly featured auditory training (AT), addressing spatial processing, dichotic listening, temporal processing and listening to speech in noise. Some interventions included cognitive or language training, assistive devices or hearing aids. Outcome measures listed included electrophysiological, AP, cognitive and language measures and questionnaires addressed to parents, teachers or the participants. (4) Conclusions: Most interventions focused on bottom-up approaches, particularly AT. A limited number of top-down approaches were observed. The compiled tools underscore the need for research on metric responsiveness and point to the inadequate consideration given to understanding how children perceive change.
PubMed: 38921276
DOI: 10.3390/healthcare12121161