Mental Retardation Research Articles

Surrogate immunohistochemistry markers in adult gliomas – Experience in a tertiary care hospital

Objectives: The recent World Health Organization classification has recommended the usage of surrogate immunohistochemical markers for molecular classification of gliomas. However, only a few studies have attempted to study the expression of the entire panel of markers. The current study was undertaken to study the association of recognized surrogate immunohistochemical markers (isocitrate dehydrogenase 1 [IDH-1], alpha-thalassemia mental retardation X-linked [ATRX] and p53) in different histological lineages and grades of adult gliomas. Materials and Methods: This study was conducted on 118 cases of adult gliomas diagnosed on histopathology over a 2-year duration in a tertiary care hospital. The expression of surrogate immunohistochemistry markers (IDH-1, ATRX, and p53) in these cases was studied. Statistical analysis: Descriptive statistical analysis with the Statistical Package for the Social Science system version 17.0. Results: The frequency of IDH-1 positivity was significantly higher in oligodendrogliomas (OG: 76.5%; oligoastrocytoma: 100%) versus astrocytoma (AS) (grades 2 and 3: 48.1%). It was also significantly higher in diffuse gliomas (grades 2 and 3) versus glioblastomas (64% vs. 16.9%). Among IDH-mutant diffuse gliomas, ATRX loss was significantly higher in AS versus OGs (84.6% vs. 7.7%). P53 overexpression correlated significantly with histological subtype (AS 2,3: 55.6% vs. OG: 5.9%). Conclusions: The surrogate immunohistochemical panel of IDH-1, ATRX, and p53 showed significant association with distinct histopathological subtypes and is helpful in molecular stratification. Cut-offs of ≥ 10% nuclear positivity for p53 and 50% loss of nuclear ATRX expression showed a good correlation.

Adherence and quality of life in patients with epilepsy in Cyprus

Abstract Introduction Epilepsy affects about 50 million people globally1. Patients often struggle with medication adherence due to forgetfulness, side effects, or lack of understanding, yet consistent use is vital for reducing seizures and improving quality of life2. Community pharmacists can improve outcomes by educating patients, aiding adherence, and clarifying drug effects and interactions, beyond just dispensing prescriptions. Aim The study aimed to assess epileptic patients’ adherence and quality of life in Cyprus. Methods This quantitative study, conducted from September 2022 to October 2023, received ethical approval from the Cyprus National Ethics Committee. Data were collected via phone calls using tools translated into Greek to assess adherence among epileptic patients. These tools included the MMAS-8 Morisky, with 8 items (7 Yes/No questions and 1 Likert 5-Point question), and the Readiness for Change scale, featuring a 0-10 ruler and 3 open-ended questions. The MARS-5, with 5 Likert 5-Point questions, and the QOLIE-31 were also used, along with demographic data collection. Inclusion criteria were patients over 18 with epilepsy, on antiepileptic therapy, and Greek-speaking. Of the 151 patients in the registry, 16 were excluded by the Neurologist of the Limassol's General Hospital due to factors like communication issues, recent stroke, quadriplegia, brain paralysis, mental retardation, and Down syndrome. Statistical analysis was performed using SPSS V28. Results In total, 85 epileptic patients participated in the study (out of the 135 patients- response rate 62.96%). The study's demographics included 47 males (55.3%) and 38 females (44.7%), with 18 participants aged 18-34 (21.2%), 46 participants aged 35-64 (54.1%), and 21 participants over 65 (24.7%). Additionally, the age of epilepsy onset was categorised as follows: 39 participants (45.9%) had an onset before 18 years of age, and 46 participants (54.1%) had an onset at 18 years of age or older. The Morisky MMAS-8 results showed 47 participants (55.3%) with high compliance, 26 (30.6%) with medium, and 12 (14.1%) with low compliance. The MARS-5 results indicated 79 participants (92.9%) had high compliance (≥20), while 6 (7.1%) had low compliance (<20). The readiness for change ruler had a mean score of 9.48 (SD = 0.16). Specifically, the distribution of scores was as follows: 1 participant (1.2%) scored 2, 4 participants (4.7%) scored 5, 2 participants (2.4%) scored 7, 4 participants (4.7%) scored 8, 2 participants (2.4%) scored 9, and 72 participants (84.7%) scored 10. The overall quality of life (QoL) score averaged 75.3 (SD = 2.16). Discussion/Conclusion This study is the first comprehensive assessment of adherence and quality of life among epileptic patients in Cyprus. Some patients did not participate due to lack of time and interest. Using the Morisky MMAS-8 and MARS-5 scales, over half showed high medication compliance, but a significant portion had medium to low compliance, indicating a need for targeted interventions. The findings underscore the critical role of community pharmacists in supporting adherence and enhancing quality of life through education, counseling, and personalized care. This study provides a foundation for future research and interventions to improve epilepsy management in Cyprus.

The investigation of visuospatial memory and visual attention in children with intellectual disability and Down syndrome

Within cognitive domains, memory and attention are among the most studied processes in people with intellectual disabilities, and studies have documented difficulties or even heterogeneities in their functioning. This study investigates the differences and similarities in the development of visuospatial memory and visual attention between children with typical development and intellectual disabilities of various etiologies. The study involved 106 children: 42 with typical development, 41 with intellectual disabilities, and 23 with Down syndrome. The sex ratio was 1:1, and the mean chronological age across groups was 8.81 years. Tools used included the Visual Information Recall Scale and Scales for Sustained Visual Attention and Visual Attention Span. Findings revealed that children with typical development outperformed the others, with statistically significant differences between groups. Notably, children with intellectual disabilities and Down syndrome also showed significant differences, highlighting the cognitive heterogeneity in intellectual disabilities.

SRPK3 Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X-Linked Intellectual Disability.

Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities. Employing exome or genome sequencing, here we identified 4 missense variants (c.475C > G; p.H159D, c.1373C > A; p.T458N, and c.1585G > A; p.E529K, c.953C > T; p.S318L) and a putative truncating variant (c.1413_1414del; p.Y471*) in the SRPK3 gene in 9 XLID patients from 5 unrelated families. To validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of SRPK3 in neurodevelopmental disorders. In post-fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability. Overall, these results suggest a crucial role of SRPK3 in the pathogenesis of syndromic X-linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024;96:914-931.

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.

Temporal development of seizure threshold and spontaneous seizures after neonatal asphyxia and the effect of prophylactic treatment with midazolam in rats

Birth asphyxia (BA) and subsequent hypoxic-ischemic encephalopathy (HIE) is one of the most serious birth complications affecting full-term infants and can result in severe disabilities including mental retardation, cerebral palsy, and epilepsy. Animal models of BA and HIE are important to characterize the functional and behavioral correlates of injury , explore cellular and molecular mechanisms, and assess the potential of novel therapeutic strategies. Here we used a non-invasive, physiologically validated rat model of BA and acute neonatal seizures that mimics many features of BA and HIE in human infants to study (i) the temporal development of epilepsy with spontaneous recurrent seizures (SRS) in the weeks and months after the initial brain injury, (ii) alterations in seizure threshold and hippocampal EEG that may precede the onset of SRS, and (iii) the effect of prophylactic treatment with midazolam. For this purpose, a total of 89 rat pups underwent asphyxia or sham asphyxia at postnatal day 11 and were examined over 8–10.5 months. In vehicle-treated animals, the incidence of electroclinical SRS progressively increased from 0 % at 2.5 months to 50 % at 6.5 months, 75 % at 8.5 months, and > 80 % at 10.5 months after asphyxia. Unexpectedly, post-asphyxial rats did not differ from sham-exposed rats in seizure threshold or interictal epileptiform discharges in the EEG. Treatment with midazolam (1 mg/kg i.p.) after asphyxia, which suppressed acute symptomatic neonatal seizures in about 60 % of the rat pups, significantly reduced the incidence of SRS regardless of its effect on neonatal seizures. This antiepileptogenic effect of midazolam adds to the recently reported prophylactic effects of this drug on BA-induced neuroinflammation, brain damage, behavioral alterations, and cognitive impairment in the rat asphyxia model of HIE.

Aplastic Anemia, Mental Retardation, and Dwarfism Syndrome Associated with Aldh2 and Adh5 Mutations

Aplastic Anemia, Mental Retardation, and Dwarfism Syndrome Associated with <i>Aldh2</i> and <i>Adh5</i> Mutations

The Relationship Between TSH and Indirect Bilirubin Levels in Neonates Suspected of Having Jaundice

Background: Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency that occurs at birth. The TSH (thyroid-stimulating hormone) test is crucial for diagnosing hypothyroidism. CH is known to cause prolonged unconjugated hyperbilirubinemia. Therefore, this study aimed to analyze the relationship between TSH and indirect bilirubin levels in neonates suspected of having jaundice. Methods: This is a non-experimental, retrospective study conducted at Lombok Dua Dua Lontar Mother and Child Hospital in Surabaya. The study involved data collection on neonates aged 2–7 days suspected of jaundice, whose TSH and indirect bilirubin levels were measured between November 2022 to April 2024. Results: Among 100 neonates, 62% were aged 2-4 days, while 38% were aged 5-7 days. The majority were male (56%), with female comprising 44%. Of the 100 neonates, only 1 (1%) had borderline TSH levels, while 99% had normal TSH levels. Hyperbilirubinemia was observed in 94% of the neonates, while 6% had normal indirect bilirubin levels. Statistical analysis using the Spearman correlation showed no significant link between TSH and indirect bilirubin levels (p = 0.802). Conclusions: While this study did not find a clear connection between TSH and indirect bilirubin levels in neonates suspected of having jaundice, one case of borderline TSH was identified. This neonate required referral to pediatric endocrinology, as untreated congenital hypothyroidism can lead to mental retardation. Despite limited research linking TSH and bilirubin levels in jaundiced neonates, routine screening for congenital hypothyroidism using TSH testing should be reconsidered. Future studies could benefit from focusing on specific causes of neonatal jaundice to help narrow down research questions in this area.

Having paid work 1 year after disability claim in different types of mental and behavioural disorders

Abstract Background The majority of claimants diagnosed with a mental and/or behavioral disorder have residual work capacity, however, the chance of actual (return to) work after a disability claim assessment may differ within this diagnosis group depending on the specific type of disease. The aim of this study is to examine the associations of different mental and behavioural diseases with having paid employment one year after the claim assessment. Methods This longitudinal register based cohort study included all work disability applicants with mental and behavioural disorders assessed with residual work capacity in the Netherlands in 2016. Data were derived from the Dutch Social Security Institute (UWV) and were linked to register data on paid employment. ICD codes were used to categorize 11 disease groups (mental retardation, autism spectrum disorders, ADHD, somatoform disorders, adjustment disorders, PTSS, anxiety, personality disorders, mood affective disorders, addictions and delusional disorders. Multivariable logistic regression analyses were conducted separately for applicants who work and not work at time of the claim assessment. Results A total of 8544 claimants (mean age 45, 56% female; n = 1915 work at baseline) were included. In the working group being diagnosed with ADHD (OR 3.05, CI 1.08-8.61) or PTSS (OR 1.45, CI 1.04-2.02) was associated with paid work, and adjustment disorder was negatively associated (OR 0.74, CI 0.56-0.97). In the not-working group, autism spectrum disorder (OR 1.51, CI 1.02-2.22), personality disorder (OR 1.36, CI 1.02-1.81) and addiction (OR 1.94, CI 1.32-2.86) was associated with return to work, and somatoform (OR 0.51, CI 0.31-0.84) disorders and mood affective disorders (OR 0.83, CI 0.70-0.99) were negatively associated. Conclusions The findings of this study show different associations between type of mental and behavioural disease groups and paid employment one year after the claim assessment. Key messages • The association of either remaining at work or return to work is different among mental and behavioural diagnosis groups, therefore a different approach is indicated. • Active interventions to facilitate return to or remain at work might be indicated in specific diagnosis groups.

WDR45 variants as a major cause for a clinically variable intellectual disability syndrome from early infancy in females.

Pathogenic variants of WD repeat domain 45 (WDR45) cause neurodegeneration with brain iron accumulation 5 (NBIA5), which is characterised by progressive neurological regression and brain iron accumulation in adulthood. Early diagnosis of NBIA5 patients is difficult because they often show only a non-specific developmental delay in childhood, but it is essential for lifelong medical management. We investigated 32 females with developmental delays for coding variants of WDR45 using Sanger sequencing. Whole-genome sequencing (WGS) and X chromosome inactivation (XCI) analysis were also performed. We identified two disease-causing variants, one of which was a novel stop-loss variant, c.1051delG p.(Val351CysfsTer60), in a female with severe developmental delay from early infancy with epileptic spasms. The XCI analysis (which we originally developed) suggested a random pattern in white blood cells. WGS did not reveal any other pathogenic variants, including those in two iron transporter genes. Together with our previous findings in the WGS study, WDR45 variants accounted for 12% (6/51) of the females with developmental delay, suggesting that WDR45 is a major gene in females with developmental delay. Pathogenic variants of WDR45 result in various phenotypes that do not necessarily correlate with variant types or XCI skewing patterns.

RAD50 Deficiency and Its Effects on Zebrafish Embryonic Development and DNA Repair Mechanisms

The MRE11-RAD50-NBS1 (MRN) complex is essential in detecting, signaling, and repairing DNA double-strand breaks (DSBs), thus maintaining genomic integrity. Mutations in RAD50 are linked to severe conditions such as microcephaly, mental retardation, and growth retardation in humans. This study investigates the developmental impact of RAD50 protein disruption in zebrafish embryos. Zebrafish embryos were treated with MIRIN (35 µM) to inhibit RAD50 and subsequently exposed to gamma-ray irradiation (15 Gy) to analyze the role of RAD50 in managing DNA damage during embryogenesis. Time-point analysis indicated that inhibiting RAD50 and ATM proteins during early embryonic stages (at 1 hpf) leads to increased embryonic mortality and abnormalities. These adverse effects were exacerbated by irradiation, underscoring the critical role of RAD50 in DNA DSB repair. The study concludes that RAD50 deficiencies can lead to embryonic lethality and human deformities due to the inability of tissues to repair DNA DSBs effectively.

Outcome of Surgery in a Patient with Blindness and Inter- Hemispheric Cyst: A Case Report

Interhemispheric cysts are rare congenital condition which is also associated with corpus callosum agenesis. Most patients present at neonatal age or early childhood with some neurological deficiency. Some patients may present at older age. Here we present a patient with acute blindness of the right eye and dimness of vision of the left eye. He had no mental retardation or other neurological deficit. His fundus showed bilateral papilloedema. His MRI showed an interhemispheric cyst with agenesis of the corpus callosum. He was urgently operated in this hospital. The cyst was approached through interhemispheric fissure. It was excised and communicated with the third ventricle. His post-operative period was uneventful. Immediately after surgery he had improvement of his vision over a period of two week. He could return to normal life following discharge. Therefore, prompt surgical intervention is important for saving vision of these patients. Bang. J Neurosurgery 2024; 13(2): 165-169

Subependymal giant cell astrocytoma in the absence of tuberous sclerosis: a case report and literature review

Introduction and Importance: Subependymal giant cell astrocytoma (SEGA) is a benign intraventricular tumor classically arising near the Foramen of Monro. SEGAs almost always present as a component of tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by lesions in multiple organs. Case Presentation: A 16-year-old male with no significant past medical history presented with headache and dizziness. Imaging revealed intraventricular mass within the left lateral ventricle; the post-contrast image showed a contrast-enhanced lesion suggestive of SEGA. Following resection, histopathological analysis identified the lesion as a SEGA. However, on further workup, the patient was found not to meet the clinical criteria of TSC, which exemplifies a rare case of SEGA in the absence of a TSC diagnosis. Clinical Discussion: Tuberous sclerosis Complex (TSC) is a neurocutaneous disorder with a classical triad of seizures, mental retardation, and hamartomas in multiple organs and tissues. SEGA without TSC does not have multiorgan problems and hence doesn’t need ancillary testing but despite having a good outlook still needs follow-up for interval growth or recurrence. However, overall prognosis of isolated SEGA is better than SEGA associated with TSC. Conclusion: SEGA is commonly found to be associated with TSC. Although it is challenging to diagnose isolated SEGA, hence it is essential for physicians to be aware of the possibility of SEGA in the absence of other characteristics of TSC, which has many implications for a patient’s clinical course. This case report adds to current knowledge regarding isolated SEGA.

Syndromic obesity in children (using the example of clinical cases)

Obesity is a heterogeneous group of hereditary and acquired diseases associated with excessive accumulation of adipose tissue in the body. One example of syndromic obesity in children is Bardet-Biedl syndrome. This is a rare autosomal recessive disease from the group of ciliopathies, characterized by retinal dystrophy, obesity, polydactyly, mental retardation, hypogonadism, and renal dysfunction. The article presents two clinical cases of Bardet-Biedl syndrome. Diagnostic criteria for the disease are given, and the need for molecular genetic research methods in the early stages of the diagnostic search is shown. Promising directions in the treatment of the syndrome are considered.

Clinical characteristics and genetic analysis of mental retardation disorder with TRIO gene variant

Objective: To summarize the clinical and genetic characteristics of mental retardation disorder (MRD) with TRIO gene variant in children. Methods: Case series study. The data of 9 children with TRIO gene variants were collected retrospectively from August 2019 to March 2024 in Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University. The data included gender, age, intellectual and motor development, appearance, seizures, neuroimaging and genetic results. The clinical features and genotype-phenotype correlations were summarized. Results: Of the 9 children, 6 boys and 3 girls, 4 MRD63 children presented with moderate to severe developmental delays accompanied by macrocephaly; 5 MRD44 children had mild to moderate developmental delays with microcephaly. A total of 5 children had dysmorphic facial features (flat occiput, thick eyebrows, unibrow, large ears, short fingers, pale skin, yellow hair, and strabismus), 2 children experienced seizures (1 child with myoclonic seizure and 1 with absence seizure), 4 children had feeding difficulties, 1 child had congenital cataracts, 1 child had congenital heart disease, 1 child had recurrent infections, and 1 child had tiger-striped changes in the fundus examination. TRIO gene variants carried by the 9 children were all de novo, involving 8 variant sites, including 7 missense variants and 1 frameshift variant, c.3232C>T/p.R1078W (2 cases), c.3920A>G/p.Y1307C, c.4112A>T/p.H1371L, c.4283G>T/p.R1428L, c.4394A>G/p.N1465S, c.6041T>C/p.I2014T, c.6821G>A/p.R2274H, c.7027delC/p.Q2343Sfs*70. Among them, 2 sites are located in the Spectrin domain, 4 sites are in the GEFD1 domain, 2 sites are in the GEFD2 domain, and 1 site (frameshift variant) is in the PH2-SH3 domain. The individual with frameshift variant exhibit absence seizures, mild developmental delay, and the mildest phenotype. The child with myoclonic seizures was treated with valproic acid and levetiracetam for seizure control, while the child with absence epilepsy was treated with valproic acid and lamotrigine for seizure control. All 9 children underwent regular rehabilitation exercises, making slow progress. Conclusions: TRIO gene related MRD is characterized by varying degrees of developmental delay, and often accompanied by macrocephaly or microcephaly, dysmorphic facial features, and with or without seizures. The main variant types are missense variants, which are mostly concentrated in the Spectran domain and GEFD domain. p. R1078W may be a relative hotspot variant. The phenotype caused by the frameshift variant is relatively milder.

Phthalate exposure induces cell death and ferroptosis in neonatal microglial cells.

Phthalates are the materials used for plasticizing polyvinyl chloride. Di-(2-Ethylhexyl) phthalate (DEHP) is one of the phthalates most frequently used in a wide range of applications, including medical equipment such as endotracheal and feeding tubes, intravenous catheters, central lines, extracorporeal membrane oxygenation sets, total parenteral nutrition bags, blood product sets, and intravenous pump lines, respiratory sets in neonatal intensive care units (NICUs). Studies have shown that phthalates, including DEHP, can cross the placenta and blood-brain barrier, possibly leading to neurodevelopmental impairment in vitro and in vivo. However, the molecular mechanisms affected by phthalate exposure have not been explored in depth. This study aimed to illuminate the effects of DEHP on neuroinflammation at the molecular level using neonatal microglial cells as the model. Mouse BV-2 neonatal microglia cells were exposed to DEHP under controlled conditions. Cellular toxicity was assessed via a cell viability assay and specific markers were used to evaluate the apoptosis/necrosis, cellular iron content, reactive oxygen species (ROS), and organelle integrity. Proinflammatory proteins were quantified using enzyme-linked immunosorbent assay, while ferroptosis was assessed using a ferroptosis blocker, and affected gene expressions were determined using quantitative reverse-transcriptase real-time polymerase chain reaction (RT-PCR). The results revealed that high concentrations of DEHP exposure increased toxicity via increased levels of ROS and inflammation. Elevated ROS levels were observed to increase the tendency for mitochondrial-lysosomal disruption, bringing about apoptosis or necrosis. Moreover, iron homeostasis was dysregulated by DEHP, which putatively triggered ferroptosis in a dose-dependent manner. This study indicates that neonatal exposure to DEHP may be linked to neurodevelopmental impairment via inflammation-related cell death and ferroptosis. The prevalence of DEHP in NICU medical devices raises concerns about potential neurodevelopmental deficits, including disorders like autism and mental retardation. These findings highlight the urgency of addressing DEHP exposure in neonatal care.

Impact of caring for patients with polyhandicap on institutional health care workers' quality of life: a cross-sectional and longitudinal evaluation.

Profound intellectual multiple disabilities or polyhandicap (PLH) is defined as a combination of profound mental retardation and serious motor deficits resulting in extreme dependence. Support for these patients is multidisciplinary, complex, and time-consuming. Thus, institutional health care workers (HCWs) face specific working conditions: frequent physical tasks, distressed families, and restricted feedback. We aimed to identify determinants of quality of life (QoL) of HCWs and to study longitudinal evolution. The study used data from the French cohort EVAL-PLH. The participants were institutional HCWs of persons with PLH (age ≥ 3 years at the time of inclusion; age at onset of cerebral lesion <3 years old). Two populations were used: (1) cross sectional study: the sample 1 includes the HCWs assessed at T2 (2020-2021); (2) longitudinal study: the sample 2 includes the HCWs assessed at both T1 (2015-2016) and T2 (2020-2021). The data collected included: sociodemographics, health status, professional variables, and psycho-comportemental aspects. QoL was assessed using WHOQOL-BREF which provides 4 scores. In comparison with French norms, the physical and social scores of QoL were significantly lower while the psychological score was significantly higher for (i) the 223 HCWs (participation rate 62%) assessed at T2 and (ii) the 61 HCWs assessed at T1 and T2. The main factors modulating QoL were age, marital status, self-perceived financial difficulties, personal chronic disease, anxiety-mood disorders, nature of coping strategies, and burnout. This study confirms the mixed (negative and positive) impact of caring persons with PLH on the institutional HCWs' QOL. Main determinants of the HCW's QOL were: older age, single status, perceived financial difficulties, altered health status, burn out and coping strategies.Clinical trial registration number: NCT02400528.

Atulyagotreeya Vivaha: A scientific review and case series on non-consanguineous marriage

Atulya Gotra Vivaha (non-consanguineous marriages), emphasized in Ayurveda and supported by modern genetics, plays a crucial role in reducing the risk of congenital anomalies and genetic disorders. Ancient Ayurvedic texts, such as Acharya Charaka’s Atulyagotreeya Sharira Adhyaya, advocate marrying outside one's Gotra to prevent the inheritance of faulty genes and ensure healthier progeny. Modern science also confirms that consanguineous marriages increase the risk of autosomal recessive disorders like mental retardation and congenital anomalies. Despite these insights, cultural norms, ignorance, and lack of awareness drive individuals, especially in less-educated communities, to practice consanguineous marriages, risking the life and health of future generations. This review highlights the need for awareness and education regarding the risks of such unions. Promoting Atulya Gotra marriages can help reduce the burden of genetic disorders and protect every child's life, which is invaluable to the well-being of society.

Epilepsy in Angelman syndrome and the most common electroencephalographic findings

Angelman syndrome is a genetic disorder characterised by severe mental retardation, subtle dysmorphic facial features, a characteristic behavioural phenotype, seizures and abnormalities in video electroencephalograms (video EEG). Angelman syndrome may be associated with genetic mechanisms involving the region of chromosome 15q11-13. Up to 90% of cases have epileptic seizures, usually in the early years of life. Videoelectroencephalography patterns with some typical characteristics associated with Angelman syndrome have been reported, although these are not specific to it, and as such it is also useful for early diagnosis, especially in the first months or years of life. To characterise the videoelectroencephalography findings of 17 patients diagnosed with Angelman syndrome, and compare them with previously published studies. We conducted a retrospective observational study of 34 video EEGs performed on 17 patients diagnosed with Angelman syndrome at the clinical neurophysiology service of the Puerta de Hierro University Hospital in Madrid between 2019 and 2022. The primary objective was to characterise the videoelectroencephalographic findings and compare them with previously published studies. As secondary objectives, we analysed the patterns proposed by Dan and Boyd, and other demographic, genetic and clinical data. Video EEG supported the clinical suspicion in our study, as baseline brain activity was altered in all the patients. We identified a pattern similar to those defined by Dan and Boyd in 88% of the cases, and the type III pattern was the most common in our series. These findings confirm that video EEG is highly sensitive for the diagnosis of Angelman syndrome, and very useful as a diagnostic biomarker in the early stages of life.

Loss of PHF6 causes spontaneous seizures, enlarged brain ventricles and altered transcription in the cortex of a mouse model of the Börjeson-Forssman-Lehmann intellectual disability syndrome.

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability and endocrine disorder caused by pathogenic variants of plant homeodomain finger gene 6 (PHF6). An understanding of the role of PHF6 in vivo in the development of the mammalian nervous system is required to advance our knowledge of how PHF6 mutations cause BFLS. Here, we show that PHF6 protein levels are greatly reduced in cells derived from a subset of patients with BFLS. We report the phenotypic, anatomical, cellular and molecular characterization of the brain in males and females in two mouse models of BFLS, namely loss of Phf6 in the germline and nervous system-specific deletion of Phf6. We show that loss of PHF6 resulted in spontaneous seizures occurring via a neural intrinsic mechanism. Histological and morphological analysis revealed a significant enlargement of the lateral ventricles in adult Phf6-deficient mice, while other brain structures and cortical lamination were normal. Phf6 deficient neural precursor cells showed a reduced capacity for self-renewal and increased differentiation into neurons. Phf6 deficient cortical neurons commenced spontaneous neuronal activity prematurely suggesting precocious neuronal maturation. We show that loss of PHF6 in the foetal cortex and isolated cortical neurons predominantly caused upregulation of genes, including Reln, Nr4a2, Slc12a5, Phip and ZIC family transcription factor genes, involved in neural development and function, providing insight into the molecular effects of loss of PHF6 in the developing brain.