Un análisis integrado entre la calidad de vida y las necesidades de apoyo de personas adultas con discapacidad intelectual en Chile / An integrated analysis between the quality of life and the support needs of adults with intellectual disabilities in Chile

El paradigma de apoyos y el de calidad de vida se han transformado en guías fundamentales para los avances en el ámbito de la discapacidad intelectual (DI). Con base en una muestra de 93 personas adultas con DI, se analiza, desde un enfoque cuantitativo no experimental, la relación entre la calidad de vida y las necesidades de apoyo, aplicando la escala INICO-FEAPS y la escala de Intensidad de Apoyos (SIS) para cada constructo. Los principales resultados evidencian que existe una relación fuerte e indirecta entre calidad de vida y necesidades de apoyos, y también la relevancia de analizar dichos resultados desde variables como grado de discapacidad, sexo o nivel socioeconómico. La discusión permite inferir la necesidad de discutir nuevas estrategias en torno a categorías como el grado de discapacidad, la autodeterminación e inclusión social, como elementos facilitadores de la calidad de vida y apoyos desde un enfoque integral que contribuya al desarrollo de estrategias de programas sociales para la población con DI. (AU)

The support paradigm and the quality of life paradigm have become fundamental guides for progress in the field of Intellectual Disability (ID). Based on a sample of 93 adults with ID, the relationship between Quality of Life and Support Needs is analyzed from a non-experimental quantitative approach, applying the INICO-FEAPS scale and the SIS Support Intensity scale for each construct. The main results show that there is a strong and indirect relationship between quality of life and support needs, and the relevance of analyzing these results from variables such as the degree of disability, sex or socioeconomic level. The discussion allows us to infer the need to discuss new strategies around categories such as the degree of disability, self-determination and social inclusion, as facilitating elements of quality of life and supporting a comprehensive approach that contributes to the development of social program strategies for the population with ID. (AU)

Beneficios y limitaciones de la planificación centrada en la persona en el campo de la discapacidad intelectual y del desarrollo: una revisión sistemática según las directrices de PRISMA / Benefits and limitations of person-centered planning in the field of intellectual and developmental disabilities: a systematic review according to PRISMA guidelines

La metodología de Planificación Centrada en la Persona (PCP) cada vez tiene mayor impacto en España. Comenzando desde las distintas legislaciones que regulan la atención a este colectivo en las diferentes autonomías y terminando en los centros que proveen este servicio. No obstante, existe escasa literatura internacional de estudios empíricos a grandes escalas que sitúen este enfoque metodológico en una posición relevante que garantice la eficacia de la PCP. El objetivo principal de este estudio es conocer el estado del uso de la metodología de PCP a través de estudios avalados empíricamente que sostengan tanto beneficios como limitaciones durante los últimos 10 años (2012-2022). Para ello, se ha realizado una revisión sistemática desde las directrices de PRISMA (2020), que incluye un total de 31 artículos. Como conclusión, se han descubierto más beneficios que limitaciones entre las que destacan las ventajas en su uso para las personas con discapacidad intelectual y del desarrollo y las mejoras de aspectos relacionados con la autodeterminación. No obstante, las limitaciones prevalecen por la falta de apoyos y recursos adecuados de las organizaciones para responder a una planificación centrada en la persona y la necesidad de formación de las personas implicadas en la elaboración de la PCP, lo que genera la incógnita de si se están realizando buenas prácticas en el uso de dicha metodología. (AU)

The methodology of Person Centered Planning (PCP) is having an increasing impact in Spain. Starting from the different legislations that regulate the attention to this group in the different autonomous regions and ending in the centers that provide this service. However, there is little international literature on large-scale empirical studies that place this methodological approach in a relevant position to guarantee the efficacy of PCP. The main objective of this study is to know the status of the use of PCP methodology through empirically supported studies that sustain both benefits and limitations during the last 10 years (2012-2022). For this purpose, a systematic review has been conducted since the PRISMA guidelines (2020), including a total of 31 articles. As a conclusion, more benefits than limitations have been found, among which the advantages in its use for people with intellectual and developmental disabilities and improvements in aspects related to self-determination stand out. However, limitations prevail due to the lack of adequate support and resources from organizations to respond to person-centered planning and the need for training of the people involved in the development of the PCP, which raises the question of whether good practices are being carried out in the use of this methodology. (AU)

Un análisis integrado entre la calidad de vida y las necesidades de apoyo de personas adultas con discapacidad intelectual en Chile / An integrated analysis between the quality of life and the support needs of adults with intellectual disabilities in Chile

El paradigma de apoyos y el de calidad de vida se han transformado en guías fundamentales para los avances en el ámbito de la discapacidad intelectual (DI). Con base en una muestra de 93 personas adultas con DI, se analiza, desde un enfoque cuantitativo no experimental, la relación entre la calidad de vida y las necesidades de apoyo, aplicando la escala INICO-FEAPS y la escala de Intensidad de Apoyos (SIS) para cada constructo. Los principales resultados evidencian que existe una relación fuerte e indirecta entre calidad de vida y necesidades de apoyos, y también la relevancia de analizar dichos resultados desde variables como grado de discapacidad, sexo o nivel socioeconómico. La discusión permite inferir la necesidad de discutir nuevas estrategias en torno a categorías como el grado de discapacidad, la autodeterminación e inclusión social, como elementos facilitadores de la calidad de vida y apoyos desde un enfoque integral que contribuya al desarrollo de estrategias de programas sociales para la población con DI. (AU)

The support paradigm and the quality of life paradigm have become fundamental guides for progress in the field of Intellectual Disability (ID). Based on a sample of 93 adults with ID, the relationship between Quality of Life and Support Needs is analyzed from a non-experimental quantitative approach, applying the INICO-FEAPS scale and the SIS Support Intensity scale for each construct. The main results show that there is a strong and indirect relationship between quality of life and support needs, and the relevance of analyzing these results from variables such as the degree of disability, sex or socioeconomic level. The discussion allows us to infer the need to discuss new strategies around categories such as the degree of disability, self-determination and social inclusion, as facilitating elements of quality of life and supporting a comprehensive approach that contributes to the development of social program strategies for the population with ID. (AU)

Beneficios y limitaciones de la planificación centrada en la persona en el campo de la discapacidad intelectual y del desarrollo: una revisión sistemática según las directrices de PRISMA / Benefits and limitations of person-centered planning in the field of intellectual and developmental disabilities: a systematic review according to PRISMA guidelines

La metodología de Planificación Centrada en la Persona (PCP) cada vez tiene mayor impacto en España. Comenzando desde las distintas legislaciones que regulan la atención a este colectivo en las diferentes autonomías y terminando en los centros que proveen este servicio. No obstante, existe escasa literatura internacional de estudios empíricos a grandes escalas que sitúen este enfoque metodológico en una posición relevante que garantice la eficacia de la PCP. El objetivo principal de este estudio es conocer el estado del uso de la metodología de PCP a través de estudios avalados empíricamente que sostengan tanto beneficios como limitaciones durante los últimos 10 años (2012-2022). Para ello, se ha realizado una revisión sistemática desde las directrices de PRISMA (2020), que incluye un total de 31 artículos. Como conclusión, se han descubierto más beneficios que limitaciones entre las que destacan las ventajas en su uso para las personas con discapacidad intelectual y del desarrollo y las mejoras de aspectos relacionados con la autodeterminación. No obstante, las limitaciones prevalecen por la falta de apoyos y recursos adecuados de las organizaciones para responder a una planificación centrada en la persona y la necesidad de formación de las personas implicadas en la elaboración de la PCP, lo que genera la incógnita de si se están realizando buenas prácticas en el uso de dicha metodología. (AU)

The methodology of Person Centered Planning (PCP) is having an increasing impact in Spain. Starting from the different legislations that regulate the attention to this group in the different autonomous regions and ending in the centers that provide this service. However, there is little international literature on large-scale empirical studies that place this methodological approach in a relevant position to guarantee the efficacy of PCP. The main objective of this study is to know the status of the use of PCP methodology through empirically supported studies that sustain both benefits and limitations during the last 10 years (2012-2022). For this purpose, a systematic review has been conducted since the PRISMA guidelines (2020), including a total of 31 articles. As a conclusion, more benefits than limitations have been found, among which the advantages in its use for people with intellectual and developmental disabilities and improvements in aspects related to self-determination stand out. However, limitations prevail due to the lack of adequate support and resources from organizations to respond to person-centered planning and the need for training of the people involved in the development of the PCP, which raises the question of whether good practices are being carried out in the use of this methodology. (AU)

A systematic review and pooled analysis of penetrance estimates of copy number variants associated with neurodevelopment.

PURPOSE: Many copy number variants (CNVs) are reported to cause a variety of neurodevelopmental disabilities including intellectual disability, developmental delay, autism and other phenotypes with incomplete penetrance, so not all individuals with a pathogenic CNV are affected. Penetrance estimates vary between studies. A systematic review was conducted to clarify CNV penetrance for 83 recurrent CNVs. METHODS: A systematic review using PRISMA guidelines (PROSPERO #CRD42021253955) was conducted to identify penetrance estimates for CNVs associated with neurodevelopment. Pooled analysis was performed using forest plots. The Ottawa Risk of Bias Assessment facilitated evaluation. RESULTS: Fifteen studies were reviewed in detail with nine affected cohorts pooled and compared against the gnomAD v4.0 CNV control cohort of 269,885 individuals. Several CNVs previously associated with non-statistically significant penetrance estimates now exhibit statistically significant differences, contributing to emerging evidence for their pathogenicity (15q24 duplication [A-D breakpoints], 15q24.2q24.5 deletion and duplication (FBXO22), 17q11.2 duplication (NF1), 17q21.31 duplication (KANSL1) and 22q11.2 distal duplication). Additionally, evidence is presented for the benign nature of some CNVs (15q11.2 duplication (NIPA1) and 2q13 proximal duplication (NPHP1)). CONCLUSION: This is a large-scale systematic review of CNVs associated with neurodevelopment. A synopsis analysing penetrance and pathogenicity is provided for each of the 83 recurrent CNVs.

The home literacy environment of school-age autistic children with high support needs.

BACKGROUND: As a group, autistic children with high support needs (with adaptive functioning in the range of an intellectual disability) are at risk of significant literacy difficulties. We investigated the parent-reported home literacy environment of this group of children. METHOD: Sixty-two parents of autistic children (4.5 to 18.25 years) attending an autism-specific school completed a home literacy survey reporting on their child's: (1) alphabet knowledge, (2) interest in reading, (3) activities/interactions around books, (4) reading ability, and (5) writing ability. RESULTS: We found significant positive correlations between parent-reported child interest in reading and literacy-related interactions and skills, but not with child age. Children using spoken words to communicate obtained significantly greater scores on four home-literacy subscales, but not on reading interest. CONCLUSIONS: A better understanding of the home literacy activities of autistic children with high-support needs is needed to inform educational practices aimed at promoting literacy development in this vulnerable population.

Effects of Texas State Agency Integration on Mental Health Service Use Among Individuals with Co-occurring Cognitive Disabilities and Mental Health Conditions.

This study uses Texas's 2017 integration of the state disability and mental health agencies as a case study, combining interviews with Texas agency and advocacy organization leaders to examine perceptions of agency integration and augmented synthetic control analyses of 2014-2020 Medical Expenditure Panel Survey to examine impacts on mental health service use among individuals with co-occurring cognitive disabilities (including intellectual and developmental disabilities) and mental health conditions. Interviewees described the intensive process of agency integration and identified primarily positive (e.g., decreased administrative burden) impacts of integration. Quantitative analyses indicated no effects of integration on receipt of mental health-related services among people with co-occurring conditions. While leaders identified some potentially beneficial impacts of state agency integration, the limited impact of integration beyond the agency suggests that interventions at multiple levels of the service system, including those targeting providers, are needed to better meet the mental health service needs for this population.

Bridging the gap: national virtual education programme for professionals caring for adults with intellectual and developmental disabilities at the time of COVID-19.

BACKGROUND: The COVID-19 pandemic significantly impacted the mental health of adults with intellectual and developmental disabilities (IDD). During this period of uncertainty and need for up-to-date information, various virtual training programmes demonstrated the role of tele-mentoring programmes. AIM: The aim of this paper is to describe the educational evaluation of the National Extension for Community Healthcare Outcomes - Adults with Intellectual and Developmental Disabilities (ECHO-AIDD), a programme for service providers working with adults with IDD during COVID-19. METHOD: The programme consisted of six sessions, conducted weekly, over two cycles. Each session included didactic teaching by hub team members, COVID-19 news updates, wellness check-ins and a brief mindfulness activity, followed by a 30 to 45 min case-based discussion. The hub structure had an inter-professional approach to team expertise. Those with lived experience were an integral part of the content experts' hub. Pre-, post- and follow-up evaluation data were collected. RESULTS: Care providers from health and social care sectors (n = 230) participated in the programme. High levels of engagement and satisfaction were reported. Self-efficacy ratings improved from pre- to post-, and were maintained at 8-week follow-up; improvement from pre- to post- was significant (P < 0.0001). CONCLUSION: Exposure to National ECHO-AIDD educational intervention led to improvement in perceived competencies. This study also shows the valuable role of people with lived experience in fostering adaptive expertise in learners. The outreach and scalability support the feasibility of building a national virtual community of practice for IDD service providers. Future studies should focus on studying the impact of these programmes on the health outcomes of people with IDD.

A Systematic Review of the Stigma Experienced by People with Autism Spectrum Disorder Associated with Intellectual Disabilities and by Their Family Caregivers.

The purpose of this paper was to explore the social stigma experienced by individuals diagnosed with ASD+ID, and to identify knowledge gaps for future studies by conducting a systematic review of peer-reviewed literature. In this systematic review, we included 12 studies exploring the experience of stigma among people with ASD+ID and/or their caregivers. Our aim was to better understand this experience, but also to explore the strategies used to cope with stigma in this population. Our results confirmed that people with ASD+ID and their caregivers experience at least low to moderate levels of stigma, and that this experience is modulated by internal and external factors (such as parental age, mindfulness traits, ASD symptoms…). In addition, our results show the impact of stigma on community integration, psychological well-being and help-seeking behaviour. The role of family, friends and professional support, as well as the formation of networks to share information, appear in our results to be protective factors against stigma. To our knowledge, this study is the first systematic review to examine the stigmatisation of people with ASD+ID and/or their caregivers. Further research is needed to understand the perspective of people with ASD+ID themselves and to explore other factors that modulate this experience, in particular gender and ethnicity.

A Germline ZFX Missense Variant in a Patient With Primary Hyperparathyroidism.

A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease.

The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants.

ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants). In this study, we describe the clinical features of 13 additional individuals and review the data on a total of 27 individuals (16 individuals with monoallelic and 11 with biallelic ANK3 variants) and demonstrate that the phenotype for biallelic variants is more severe. The phenotypic features include language delay (92%), autism spectrum disorder (76%), intellectual disability (78%), hypotonia (65%), motor delay (68%), attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) (57%), sleep disturbances (50%), aggressivity/self-injury (37.5%), and epilepsy (35%). A notable phenotypic difference was presence of ataxia in three individuals with biallelic variants, but in none of the individuals with monoallelic variants. While the majority of the monoallelic variants are predicted to result in a truncated protein, biallelic variants are almost exclusively missense. Moreover, mono- and biallelic variants appear to be localized differently across the three different ankyrin-G isoforms, suggesting isoform-specific pathological mechanisms.

Expanding the phenotype of neurofibromatosis type 1 microdeletion syndrome.

Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics. This cohort consists of 57 individuals with NF-1 microdeletion syndrome (28 type-1, 4 type-2, 2 type-3, 9 atypical deletions, and 14 indeterminate). We note 38/56 (67.9%) with describable facial features, 25/57 (43.8%) with plexiform neurofibromas, and 3/57 (5.2%) with malignant peripheral nerve sheath tumors within the observed period. The most reported neurodevelopmental manifestations from school-age or older individuals included 39/49 (79.6%) with developmental delays, 35/49 (71.4%) with expressive and/or receptive speech delays, 33/41 (80.5%) with learning difficulties, and 23/42 (54.8%) with attention-deficit/hyperactivity disorder. Full-scale IQ testing data was available for 22 individuals (range: 50-96). Of the 21 adults in this cohort, 14/21 (66.7%) graduated from high school, and 4/21 (19.0%) had some college experience. Many individuals received academic support (i.e., special education, individual education plan). In this cohort, neurocognitive outcomes in adults varied more than typically reported in the literature.

Rethinking the Accessibility of Hearing Assessments for Children with Developmental Disabilities.

We aim to determine the accessibility of gold-standard hearing assessments - audiogram or auditory brainstem response (ABR) - during the first 3 months of hearing health care for children with and without developmental disabilities. Electronic health records were examined from children (0-18 years) who received hearing health care at three hospitals. Children with developmental disabilities had a diagnosis of autism, cerebral palsy, Down syndrome, or intellectual disability. Assessments from the first 3 months were reviewed to determine if ≥ 1 audiogram or ABR threshold was recorded. To evaluate differences in assessment based on disability status, logistic regression models were built while accounting for age, race, ethnicity, sex, and site. Of the 131,783 children, 9.8% had developmental disabilities. Whereas 9.3% of children in the comparison group did not access a gold-standard assessment, this rate was 24.4% for children with developmental disabilities (relative risk (RR) = 3.79; p < 0.001). All subgroups were at higher risk relative to the comparison group (all p < 0.001): multiple diagnoses (RR = 13.24), intellectual disabilities (RR = 11.52), cerebral palsy (RR = 9.87), Down syndrome (RR = 6.14), and autism (RR = 2.88). Children with developmental disabilities are at high risk for suboptimal hearing evaluations that lack a gold-standard assessment. Failure to access a gold-standard assessment results in children being at risk for late or missed diagnosis for reduced hearing. Results highlight the need for (1) close monitoring of hearing by healthcare providers, and (2) advancements in testing methods and guidelines.

[NFIX gene mutation causes Marshall-Smith syndrome in a pair of identical twins and literature review]. / NFIXåŸºå› å˜å¼‚å¯¼è‡´ä¸€å¯¹åŒåµåŒèƒžèƒŽMarshall-Smithç»¼åˆå¾å¹¶æ–‡çŒ®å¤ä¹ .

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.

Multicenter retrospective study of patients with PCDH19-related epilepsy: The first Hungarian cohort.

OBJECTIVE: PCDH19-related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin-19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated. METHODS: In our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19. RESULTS: In the Hungarian patient population aged 0-18 years, the prevalence of PCDH19-related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4-5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam. SIGNIFICANCE: The prevalence of PCDH19-related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.

Fragile X Syndrome and FMR1 premutation: results from a survey on associated conditions and treatment priorities in Italy.

BACKGROUND AND OBJECTIVES: Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability, caused by CGG-repeat expansions (> 200) in the FMR1 gene leading to lack of expression. Espansion between 55 and 200 triplets fall within the premutation range (PM) and can lead to different clinical conditions, including fragile X- primary ovarian insufficiency (FXPOI), fragile X-associated neuropsychiatric disorders (FXAND) and fragile X-associated tremor/ataxia syndrome (FXTAS). Although there is not a current cure for FXS and for the Fragile X-PM associated conditions (FXPAC), timely diagnosis as well as the implementation of treatment strategies, psychoeducation and behavioral intervention may improve the quality of life (QoL) of people with FXS or FXPAC. With the aim to investigate the main areas of concerns and the priorities of treatment in these populations, the Italian National Fragile X Association in collaboration with Bambino Gesù Children's Hospital, conducted a survey among Italian participants. METHOD: Here, we present a survey based on the previous study that Weber and colleagues conducted in 2019 and that aimed to investigate the main symptoms and challenges in American individuals with FXS. The survey has been translated into Italian language to explore FXS needs of treatment also among Italian individuals affected by FXS, family members, caretakers, and professionals. Furthermore, we added a section designated only to people with PM, to investigate the main symptoms, daily living challenges and treatment priorities. RESULTS: Anxiety, challenging behaviors, language difficulties and learning disabilities were considered the major areas of concern in FXS, while PM was reported as strongly associated to cognitive problems, social anxiety, and overthinking. Anxiety was reported as a treatment priority in both FXS and PM. CONCLUSION: FXS and PM can be associated with a range of cognitive, affective, and physical health complications. Taking a patient-first perspective may help clinicians to better characterize the cognitive-behavioral phenotype associated to these conditions, and eventually to implement tailored therapeutic approaches.

Effectiveness of Online Programmes for Family Carers of People with Intellectual Disabilities: Systematic Review of the International Evidence Base.

This systematic literature review examines the evidence base on the effectiveness of online programmes on the mental health and well-being of family carers of people with intellectual disabilities. Databases (ERIC, Medline, PsycINFO and CINAHL) were searched for intervention studies that considered online interventions for family carers of people with intellectual disabilities. Data were extracted using standardised data extraction tools. Bias was assessed using the Cochrane risk of bias tool for randomised trials (RoB 2). Screening, extraction and assessment of bias were completed independently by two members of the research team. Given the low number of included studies and different outcomes assessed within them, it was not possible to conduct a meta-analysis; therefore, data are presented narratively. Two studies met the criteria to be included in the review. Both studies utilised a feasibility randomised controlled trial methodology. One study found a significant decrease in parental stress, while the other found a significant increase in psychological well-being. Caution must be taken in drawing firm conclusions, given the small sample sizes and low retention rates in both studies. Online programmes seem to offer potential benefits to family carers of people with intellectual disabilities. However, further investigation is needed to examine these programmes, adopting a collaborative approach with family carers.

Case report: An adolescent female with anosmic hypogonadotropic hypogonadism, intellectual disability, and papillary thyroid carcinoma: heterozygous deletion of TCF12.

Background: Isolated hypogonadotropic hypogonadism is a heterogeneous clinical entity. There is a growing list of molecular defects that are associated with hypogonadotropic hypogonadism (HH). TCF12, a recently identified molecular defect, causes craniosynostosis and is suggested to be used as a biomarker for prognosis in various cancer types. Recently, TCF12 variants were shown in a cohort with HH. Case presentation: A 15.3 years old female patient was referred to the endocrinology clinic for obesity. She had been gaining weight from mid-childhood. She had her first epileptic seizure at the age of 15.1 years and mildly elevated thyroid autoantibodies were detected during evaluation for etiology of seizures. She had not experienced menarche yet. She was operated for left strabismus at the age of 7 years. School performance was poor and she was receiving special education. Tanner stage of breast was 1 and pubic hair was 3. The endocrine workup revealed hypogonadotropic hypogonadism. Also, the Sniffin' Sticks test detected anosmia. Thyroid ultrasonography was performed due to the mildly elevated thyroid autoantibodies, and thyroid nodules with punctate calcifications were detected. Total thyroidectomy and central lymph node dissection were performed regarding the cytological findings of the nodules and multicentric papillary thyroid carcinoma with no lymph node metastasis was detected on pathology specimens. Regarding the phenotypic features of the patients, whole exome sequencing was performed and heterozygous deletion of exon 1 and exon 6-8 in TCF12 was detected. Conclusion: Haploinsufficiency of TCF12 causes anosmic HH. Probably due to the incomplete penetrance and variable expressivity of the disease, patients could display variable phenotypic features such as intellectual disability, developmental delay, and craniosynostosis. Further description of new cases with TCF12 variations could enhance our understanding of craniosynostosis and its potential link to Kallmann syndrome associated with this gene.

Dynamic regulation of alternative polyadenylation by PQBP1 during neurogenesis.

Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3' untranslated regions (3' UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders.

Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

BACKGROUND: SINO syndrome (Spastic paraplegia, Intellectual disability, Nystagmus and Obesity) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising eight with SINO and four with an autosomal recessive condition attributed to bi-allelic KIDINS220 variants. METHODS: In our international cohort, we have comprised 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed clinical and molecular data of our cohort and previously reported individuals and based on functional experiments reached a better understanding of the pathogenesis behind KIDINS220-related disease. RESULTS: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. 92% had their diagnosis within three years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted. CONCLUSION: Our study provides further insights into the clinical spectrum, etiology and predicted functional impact of KIDINS220 variants.