The largest group of recipients of pediatric gastrostomy have neurological impairment with intellectual disability (ID). This study investigated trends in first gastrostomy insertion according to ...markers of disadvantage and ID etiology. Linked administrative and health data collected over a 32-year study period (1983–2014) for children with ID born between 1983 and 2009 in Western Australia were examined. The annual incidence rate change over calendar year was calculated for all children and according to socioeconomic status, geographical remoteness, and Aboriginality. The most likely causes of ID were identified using available diagnosis codes in the linked data set. Of 11,729 children with ID, 325 (2.8%) received a first gastrostomy within the study period. The incidence rate was highest in the 0–2 age group and there was an increasing incidence trend with calendar time for each age group under 6 years of age. This rate change was greatest in children from the lowest socioeconomic status quintile, who lived in regional/remote areas or who were Aboriginal. The two largest identified groups of ID were genetically caused syndromes (15.1%) and neonatal encephalopathy (14.8%).
Conclusion
: Gastrostomy is increasingly used in multiple neurological conditions associated with ID, with no apparent accessibility barriers in terms of socioeconomic status, remoteness, or Aboriginality.
What is Known:
•
The use of gastrostomy insertion in pediatrics is increasing and the most common recipients during childhood have neurological impairment, most of whom also have intellectual disability (ID).
What is New:
•
Nearly 3% of children with ID had gastrostomy insertion performed, with the highest incidence in children under 3 years of age
.
•
Gastrostomy use across different social groups was equitable in the Australian setting
.
Patients with mutations in Cyclin M2 (CNNM2) suffer from hypomagnesaemia, seizures, and intellectual disability. Although the molecular function of CNNM2 is under debate, the protein is considered ...essential for renal Mg
reabsorption. Here, we used a Cnnm2 knock out mouse model, generated by CRISPR/Cas9 technology, to assess the role of CNNM2 in Mg
homeostasis. Breeding Cnnm2
mice resulted in a Mendelian distribution at embryonic day 18. Nevertheless, only four Cnnm2
pups were born alive. The Cnnm2
pups had a significantly lower serum Mg
concentration compared to wildtype littermates. Subsequently, adult Cnnm2
mice were fed with low, control, or high Mg
diets for two weeks. Adult Cnnm2
mice showed mild hypomagnesaemia compared to Cnnm2
mice and increased serum Ca
levels, independent of dietary Mg
intake. Faecal analysis displayed increased Mg
and Ca
excretion in the Cnnm2
mice. Transcriptional profiling of Trpm6, Trpm7, and Slc41a1 in kidneys and colon did not reveal effects based on genotype. Microcomputed tomography analysis of the femurs demonstrated equal bone morphology and density. In conclusion, CNNM2 is vital for embryonic development and Mg
homeostasis. Our data suggest a previously undescribed role of CNNM2 in the intestine, which may contribute to the Mg
deficiency in mice and patients.
Antiseizure medications (ASMs) are the second most widely prescribed psychotropic for people with intellectual disabilities in England. Multiple psychotropic prescribing is prevalent in almost half ...of people with intellectual disabilities on ASMs. This analysis identifies limited evidence of ASM benefit in challenging behaviour management and suggests improvements needed to inform clinical practice.
SCAF4-related syndromic intellectual disability Carvalho, Laura Machado Lara; Pinto, Carla Franchi; de Oliveira Scliar, Marília ...
American journal of medical genetics. Part A,
02/2023, Volume:
191, Issue:
2
Journal Article
Peer reviewed
The causal link between variants in the SCAF4 gene and a syndromic form of intellectual disability (ID) was established in 2020 by Fliedner et al. Since then, no additional cases have been reported. ...We performed exome sequencing in a 16-year-old Brazilian male presenting with ID, epilepsy, behavioral problems, speech impairment, facial dysmorphisms, heart malformations, and obesity. A de novo pathogenic variant SCAF4(NM_020706.2):c.374_375dup(p.Glu126LeufsTer20) was identified. This is the second study reporting the involvement of SCAF4 in syndromic ID, and the description of the patient's clinical features contributes to defining the phenotypic spectrum of this recently described Mendelian disorder.
Rethinking genetic disease Sullivan, Bill
Science (American Association for the Advancement of Science),
05/2022, Volume:
376, Issue:
6594
Journal Article
Peer reviewed
Carriers of the fragile X premutation can experience medical conditions of their own
Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with ...DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS. We analyzed the metabolomic profiles of plasma samples from 129 subjects with DS and 46 healthy control (CTRL) subjects by
H Nuclear Magnetic Resonance (NMR). Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to 94% accuracy) between the two groups. The univariate analysis revealed a significant alteration in 7 metabolites out of 28 assigned unambiguously. Correlations among the metabolite levels in DS and CTRL groups were separately investigated and statistically significant relationships appeared. On the contrary, statistically significant correlations among the NMR-detectable part of DS plasma metabolome and the different intelligence quotient ranges obtained by Griffiths-III or WPPSI-III tests were not found. Even if metabolic imbalance provides a clear discrimination between DS and CTRL groups, it appears that the investigated metabolomic profiles cannot be associated with the degree of ID.
Autism spectrum disorder (ASD) and intellectual disability (ID) are heterogenous and prevalent conditions which may occur in isolation or as a co-morbidity. Psychiatric co-morbidity is common with ...limited treatment options. Preliminary research into electroconvulsive therapy (ECT) for these conditions has been encouraging. Thus, further research in this patient population is warranted. We conducted a 10-year retrospective review of the electronic medical record and identified intellectually capable individuals with ASD (IC-ASD), and those with ASD+ID or ID who received at least three ECT treatments. 32 patients were identified of which 30 (94%) experienced positive clinical response, defined as a clinical global impression-improvement (CGI-I) score of 3 or less. The average retrospective CGI-I score across all groups was 1.97, and results of a t-test performed on CGI-I scores indicated improvement across all groups t = − 16.54, df = 31, p < 0.001, 95% CI = (1.72, 2.22). No significant adverse events were identified based on clinical documentation. Our findings further support previous ECT research in this patient population.
Brunner syndrome is a recessive X-linked disorder caused by pathogenic variants in the monoamine oxidase A gene (MAOA). It is characterized by distinctive aggressive behavior, mild intellectual ...disability, sleep disturbances, and typical biochemical alterations deriving from the impaired monoamine metabolism. We herein describe a 5-year-old boy with developmental delay, autistic features, and myoclonic epilepsy, and his mother, who had mild intellectual disability and recurrent episodes of palpitations, headache, abdominal pain, and abdominal bloating. Whole exome sequencing allowed detection of the maternally-inherited variant c.410A>G, (p.Glu137Gly) in the MAOA gene. The subsequent biochemical studies confirmed the MAOA deficiency both in the child and his mother. Given the serotonergic symptoms associated with high serotonin levels found in the mother, treatment with a serotonin reuptake inhibitor and dietary modifications were carried out, resulting in regression of the biochemical abnormalities and partial reduction of symptoms. Our report expands the phenotypic spectrum of Brunner disease, bringing new perspectives on the behavioral and neurodevelopmental phenotype from childhood to adulthood.
Although many studies document an association between attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID), little is known about the etiology of this comorbidity and how ...it should be addressed in clinical settings. We sought to clarify this issue.
All individuals born in Sweden between 1987 and 2006 (n = 2,049,587) were identified using the Medical Birth Register (MBR). From this we selected 7 cohorts of relatives: 1,899,654 parent-offspring pairs, 4,180 monozygotic twin pairs, 12,655 dizygotic twin pairs, 914,848 full sibling pairs, 136,962 maternal half-sibling pairs, 134,502 paternal half-sibling pairs, and 2,790,164 full cousin pairs. We used within-individual and within-family analyses to assess the association between ADHD and ID.
Individuals with ID were at increased risk for ADHD compared to those without ID, and relatives of participants with ID were at increased risk of ADHD compared with relatives of those without ID. The magnitude of this association was positively associated with the fraction of the genome shared by the relative pair and was lower for severe compared with mild and moderate ID. Model-fitting analyses demonstrated that 91% of the correlation between the liabilities of ADHD and ID was attributable to genetic factors.
These data provide evidence that nearly all of the comorbidity between ADHD and ID can be attributed to genetic factors, which has implications for diagnostic practice.
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