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Frontiers in Endocrinology 2024Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations...
BACKGROUND
Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.
METHODS
We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.
RESULTS
Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.
CONCLUSION
Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.
Topics: Humans; Hedgehog Proteins; Pituitary Diseases; Pituitary Gland; Hypopituitarism; Mutation; Syndrome
PubMed: 38464967
DOI: 10.3389/fendo.2024.1338781 -
Molecular Genetics & Genomic Medicine Mar 2024Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual... (Review)
Review
BACKGROUND
Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.
METHODS
We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS
We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSION
We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
Topics: Adult; Female; Humans; Asian People; Databases, Factual; Genotype; Intellectual Disability; Phenotype
PubMed: 38444259
DOI: 10.1002/mgg3.2398 -
Neurotherapeutics : the Journal of the... Apr 2024Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological... (Review)
Review
Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field.
Topics: Humans; Prader-Willi Syndrome; Vagus Nerve Stimulation; Transcranial Magnetic Stimulation; Deep Brain Stimulation; Transcranial Direct Current Stimulation
PubMed: 38430811
DOI: 10.1016/j.neurot.2024.e00339 -
BMC Primary Care Feb 2024Foetal alcohol spectrum disorder (FASD) is the leading preventable cause of nongenetic mental disability. Given the patient care pathway, the General Practitioner (GP)... (Review)
Review
BACKGROUND
Foetal alcohol spectrum disorder (FASD) is the leading preventable cause of nongenetic mental disability. Given the patient care pathway, the General Practitioner (GP) is in the front line of prevention and identification of FASD. Acknowledging the importance of the prevalence of FASD, general practitioners are in the front line both for the detection and diagnosis of FASD and for the message of prevention to women of childbearing age as well as for the follow-up.
OBJECTIVES
The main objective of the scoping review was to propose a reference for interventions that can be implemented by a GP with women of childbearing age, their partners and patients with FASD. The final aim of this review is to contribute to the improvement of knowledge and quality of care of patients with FASD.
METHODS
A scoping review was performed using databases of peer-reviewed articles following PRISMA guidelines. The search strategy was based on the selection and consultation of articles on five digital resources. The advanced search of these publications was established using the keywords for different variations of FASD: "fetal alcohol syndrome," "fetal alcohol spectrum disorder," "general medicine," "primary care," "primary care"; searched in French and English.
RESULTS
Twenty-three articles meeting the search criteria were selected. The interventions of GPs in the management of patients with FASD are multiple: prevention, identification, diagnosis, follow-up, education, and the role of coordinator for patients, their families, and pregnant women and their partners. FASD seems still underdiagnosed.
CONCLUSION
The interventions of GPs in the management of patients with FASD are comprehensive: prevention, identification, diagnosis, follow-up, education, and the role of coordinator for patients, their families, and pregnant women and their partners. Prevention interventions would decrease the incidence of FASD, thereby reducing the incidence of mental retardation, developmental delays, and social, educational and legal issues. A further study with a cluster randomized trial with a group of primary care practitioners trained in screening for alcohol use during pregnancy would be useful to measure the impact of training on the alcohol use of women of childbearing age and on the clinical status of their children.
Topics: Child; Humans; Female; Pregnancy; Fetal Alcohol Spectrum Disorders; Alcohol Drinking; Maternal-Fetal Exchange; Educational Status; General Practitioners; Randomized Controlled Trials as Topic
PubMed: 38388880
DOI: 10.1186/s12875-024-02291-x -
Pediatric Neurology Apr 2024Cerebral palsy (CP) is a clinical diagnosis and was long categorized as an acquired disorder, but more and more genetic etiologies are being identified. This review aims... (Review)
Review
BACKGROUND
Cerebral palsy (CP) is a clinical diagnosis and was long categorized as an acquired disorder, but more and more genetic etiologies are being identified. This review aims to identify the clinical characteristics that are associated with genetic CP to aid clinicians in selecting candidates for genetic testing.
METHODS
The PubMed database was systematically searched to identify genes associated with CP. The clinical characteristics accompanying these genetic forms of CP were compared with published data of large CP populations resulting in the identification of potential indicators of genetic CP.
RESULLTS
Of 1930 articles retrieved, 134 were included. In these, 55 CP genes (described in two or more cases, n = 272) and 79 candidate genes (described in only one case) were reported. The most frequently CP-associated genes were PLP1 (21 cases), ARG1 (17 cases), and CTNNB1 (13 cases). Dyskinesia and the absence of spasticity were identified as strong potential indicators of genetic CP. Presence of intellectual disability, no preterm birth, and no unilateral distribution of symptoms were classified as moderate genetic indicators.
CONCLUSIONS
Genetic causes of CP are increasingly identified. The clinical characteristics associated with genetic CP can aid clinicians regarding to which individual with CP to offer genetic testing. The identified potential genetic indicators need to be validated in large CP cohorts but can provide the first step toward a diagnostic algorithm for genetic CP.
Topics: Female; Humans; Cerebral Palsy; Premature Birth; Dyskinesias; Muscle Spasticity; Intellectual Disability
PubMed: 38382247
DOI: 10.1016/j.pediatrneurol.2024.01.025 -
European Journal of Paediatric... Mar 2024To conduct a systematic review of post-neonatal neurological outcomes and mortality following neonatal seizures with electroencephalographical verification.
AIM
To conduct a systematic review of post-neonatal neurological outcomes and mortality following neonatal seizures with electroencephalographical verification.
METHODS
The databases Medline, Embase and Web of Science were searched for eligible studies. All abstracts were screened in a blinded fashion between research team members and reports found eligible were obtained and screened in full text by two members each. From studies included, outcome results for post-neonatal epilepsy, cerebral palsy, intellectual disability, developmental delay, mortality during and after the neonatal period and composite outcomes were extracted. A quality assessment of each study was performed.
RESULTS
In total, 5518 records were screened and 260 read in full text. Subsequently, 31 studies were included, containing cohorts of either mixed or homogenous etiologies. Follow-up time and gestational ages varied between studies. No meta-analysis could be performed due to the low number of studies with comparable outcomes and effect measures. Reported cumulative incidences of outcomes varied greatly between studies. For post-neonatal epilepsy the reported incidence was 5-84%, for cerebral palsy 9-78%, for intellectual disability 24-67%, for developmental delay 10-67% and for mortality 1-62%. Subgroup analysis had more coherent results and in cohorts with status epilepticus a higher incidence of post-neonatal epilepsy from 46 to 84% was shown.
CONCLUSION
The large variation of reported incidences for neurological outcomes and mortality found even when restricting to cohorts with electroencephalographically verified neonatal seizures indicates selection bias as a significant confounder in existing studies. Population-based approaches are thus warranted to correctly predict outcomes in this group.
Topics: Humans; Infant, Newborn; Cerebral Palsy; Developmental Disabilities; Electroencephalography; Seizures
PubMed: 38367369
DOI: 10.1016/j.ejpn.2024.02.005 -
Orphanet Journal of Rare Diseases Feb 2024Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal... (Review)
Review
BACKGROUND
Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal locus 15q11-13. This absence of expression occurs as a consequence of a deletion on the chromosome 15 of paternal origin (ca. 70%), a chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), or an imprinting centre defect (IC; ca. 1-3%). At birth, individuals with PWS are severely hypotonic and fail to thrive. Hyperphagia and characteristic physical and neuropsychiatric phenotypes become apparent during childhood. The risk for the development of a co-morbid psychotic illness increases during the teenage years, specifically in those with PWS due to the presence of an mUPD. The primary aim of this literature review is to inform clinical practice. To achieve this, we have undertaken a systematic analysis of the clinical research literature on prevalence, presentation, course, characteristics, diagnosis and treatment of psychotic illness in people with PWS. The secondary aim is to identify clinical aspects of psychotic illness in PWS in need of further investigation.
METHODS AND FINDINGS
A systematic literature review on psychosis in PWS was conducted on the databases Web of Knowledge, PubMed and Scopus, using the terms "((Prader-Willi syndrome) OR (Prader Willi Syndrome)) AND ((psychosis) OR (psychotic illness))". All articles written in English and reporting original human research were reviewed. In all but three of the 16 cohort studies in which the genetic types were known, the authors reported higher rates of psychosis in people with PWS resulting from an mUPD, compared to those with the deletion subtype of PWS. When psychosis was present the presentation was psychosis similar regardless of genetic type and was usually characterised by an acute onset of hallucinations and delusions accompanied by confusion, anxiety and motor symptoms.
CONCLUSIONS
The onset of confusion, an affective cyclical pattern with the presence of abnormal mental beliefs and experiences, usually of rapid onset is suggestive of the development of psychotic illness. Phenomenologically, this psychosis in people with PWS is atypical in comparison to schizophrenia and bipolar disorder in the general population. The relationship to psychosis in the general population and the optimum treatments remain uncertain.
Topics: Adolescent; Infant, Newborn; Humans; Prader-Willi Syndrome; Psychotic Disorders; Comorbidity; Family; Anxiety; Chromosomes, Human, Pair 15
PubMed: 38360662
DOI: 10.1186/s13023-024-03026-y -
BMC Public Health Feb 2024The aim of the study was to identify the variables of the internal compensatory mechanisms that differentiate the body build and posture of people with Down syndrome...
BACKGROUND
The aim of the study was to identify the variables of the internal compensatory mechanisms that differentiate the body build and posture of people with Down syndrome (DS) from the intellectual disability (ID) population. It was assumed that gaining knowledge in the abovementioned aspect will allow for a better understanding of the limitation of the kinesthetic abilities of people with ID and DS and simultaneously enable to optimize the process of planning and interventions to improve physical activity in this population with the adequate use of theirs strengths in the biomechanical and morphofunctional systems.
METHODS
The methodology of this systematic review was developed according to the PRISMA guidelines. A search of PubMed, EBSCO, Scopus databases was conducted to identify all studies on DS/ID and the body build and posture from 2003 to 2023.
RESULTS
395 articles were assessed to determine eligibility, while 22 studies met the inclusion criteria and were subjected to detailed analysis and assessment of their methodological quality. The differentiation of the body build and posture in DS population can be induced by both internal and external compensatory mechanisms. It is difficult to confirm the direct effect of the intrinsic variables that impact the body build and posture in the ID population, excluding people with DS.
CONCLUSIONS
Compared to other ID, the intrinsic differences in the body build and posture in DS individuals were induced by gender, age, and level of ID. The tendency for diversity between DS and other ID populations in body build and posture may be determined by the presence of the third copy of chromosome 21 in DS group. Internal compensatory processes may be induced mainly by abnormalities in the structure of the cervical vertebrae and feet. IQ should not be used as the only variable that identifies the population of people with ID.
Topics: Humans; Down Syndrome; Intellectual Disability; Somatotypes; Exercise; Posture
PubMed: 38326795
DOI: 10.1186/s12889-024-17908-0 -
Frontiers in Pediatrics 2024Developmental language disorder (DLD) is a common childhood condition negatively influencing communication and psychosocial development. An increasing number of... (Review)
Review
INTRODUCTION
Developmental language disorder (DLD) is a common childhood condition negatively influencing communication and psychosocial development. An increasing number of pathogenic variants or chromosomal anomalies possibly related to DLD have been identified. To provide a base for accurate clinical genetic diagnostic work-up for DLD patients, understanding the specific genetic background is crucial. This study aims to give a systematic literature overview of pathogenic variants or chromosomal anomalies causative for DLD in children.
METHODS
We conducted a systematic search in PubMed and Embase on available literature related to the genetic background of diagnosed DLD in children. Included papers were critically appraised before data extraction. An additional search in OMIM was performed to see if the described DLD genes are associated with a broader clinical spectrum.
RESULTS
The search resulted in 15,842 papers. After assessing eligibility, 47 studies remained, of which 25 studies related to sex chromosome aneuploidies and 15 papers concerned other chromosomal anomalies (SCAs) and/or Copy Number Variants (CNVs), including del15q13.1-13.3 and del16p11.2. The remaining 7 studies displayed a variety of gene variants. 45 (candidate) genes related to language development, including , , , and . After an additional search in the OMIM database, 22 of these genes were associated with a genetic disorder with a broader clinical spectrum, including intellectual disability, epilepsy, and/or autism.
CONCLUSION
Our study illustrates that DLD can be related to SCAs and specific CNV's. The reported (candidate) genes ( = 45) in the latter category reflect the genetic heterogeneity and support DLD without any comorbidities and syndromic language disorder have an overlapping genetic etiology.
PubMed: 38298611
DOI: 10.3389/fped.2024.1315229 -
Frontiers in Psychiatry 2023People with intellectual disabilities (ID) are at increased risk for developing Post Traumatic Stress Disorder (PTSD). Emerging evidence indicates that Eye Movement... (Review)
Review
INTRODUCTION
People with intellectual disabilities (ID) are at increased risk for developing Post Traumatic Stress Disorder (PTSD). Emerging evidence indicates that Eye Movement Desensitization and Reprocessing (EMDR) therapy is feasible and potentially effective for this group. However, communication, cognition, stress regulation, and attachment difficulties may interfere with the EMDR process. Adaptation of the EMDR protocol seems therefore required for this population.
AIM
This review aims to systematically identify and categorize the difficulties in applying EMDR to people with ID and the adaptations made by therapists to overcome these challenges.
METHODS
A literature search was performed in May 2023. Article selection was based on inclusion and exclusion criteria and quality appraisal.
RESULTS
After screening, 13 articles remained for further review. The identified difficulties and adaptations were categorized into the three domains of adaptive functioning (i.e., conceptual, social, and practical functioning). Considerable difficulties in applying the EMDR protocol for this group were reported. The adaptations made by therapists to overcome these difficulties were highly variable. They could be divided into three main categories: adaptions in EMDR delivery (e.g., tuning to the developmental level of the client, simplifying language, decreasing pace), involvement of others (e.g., involving family or support staff during or in between sessions), and the therapeutic relationship (e.g., taking more time, supportive attitude).
DISCUSSION
The variability of the number of mentioned difficulties and adaptations per study seems to be partly related to the specific EMDR protocol that was used. In particular, when the Shapiro adult protocol was administered, relatively more detailed difficulties and adaptations were described than in publications based on derived existing versions of an EMDR protocol for children and adolescents. A probable explanation is that already embedded modifications in these protocols facilitate the needed attunement to the client's level of functioning.
PRACTICAL IMPLICATIONS
The authors of this review suggest that EMDR protocols for children and adolescents could be adapted for people with an intellectual disability. Further research should focus on the involvement of trusted others in EMDR therapy for people with ID and the therapeutic relationship from an attachment and relational-based perspective.
PubMed: 38274435
DOI: 10.3389/fpsyt.2023.1328310