Editorial Comment: Fraternal Twins With Autism, Severe Cognitive Deficit, and Epilepsy: Diagnostic Role of Chromosomal Microarray Analysis

This article by Dr. Imitola and colleagues reports a case of monozygotic twins with pathogenic copy-number changes that include biallelic deletions of the neurexin-1 (NRXN1) gene. This case wonderfully highlights several of the salient aspects of the genetic features of autism. First, it is worth emphasizing that autism is indeed a neurogenetic disorder. In fact, the reported heritability of autism approaches 0.9 (90%). It is always important to emphasize this fact to families and to continue to advocate for timely and appropriate immunizations of all children—not hindered by the unsubstantiated fear of immunization-invoked autism.
Source: Seminars in Pediatric Neurology - Category: Neurology Authors: Source Type: research

Related Links:

Authors: Morris G, Maes M, Berk M, Carvalho AF, Puri BK Abstract Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson's disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurode...
Source: Journal of the Association of European Psychiatrists - Category: Psychiatry Tags: Eur Psychiatry Source Type: research
Conclusion: PCDH19 is a major causative gene in patients with epilepsy and further data is required to gain a better understanding of phenotype-genotype correlation. In addition to gene sequencing, deletion/duplication analysis will improve the molecular diagnosis in patients with clinical findings.
Source: Annals of Indian Academy of Neurology - Category: Neurology Authors: Source Type: research
Neuropediatrics DOI: 10.1055/s-0040-1701694Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is a severe developmental and epileptic encephalopathy caused by loss-of-function mutations in one copy of SCN1A (haploinsufficiency), located on chromosome 2q24, with decreased function of Nav1.1 sodium channels in GABAergic inhibitory interneurons. Pharmacoresistant seizures in DS start in the infancy in the form of hemiclonic febrile status epilepticus. Later, other intractable seizure types develop including myoclonic seizures. Early normal development in infancy evolves into moderate to severe int...
Source: Neuropediatrics - Category: Neurology Authors: Tags: Review Article Source Type: research
AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/C...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsThis study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and r...
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
We report two independent subjects with 16q12.1q21 deletion syndrome presenting with dysmorphic facial features, developmental delay, strabismus, and aggressive behavior. A minimal region of overlap spanning 1.7 Mb on chromosome 16, including IRX5, GNAO1, and NUDT21 genes was shared among these two cases and those previously reported. This minimal region of overlap suggests the potential pathogenic role of these genes, previously implicated in diseases of the central nervous system. PMID: 32045705 [PubMed - as supplied by publisher]
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
AbstractAutism spectrum disorder (ASD) is a neuronal developmental disorder with impaired social interaction and communication, often with abnormal intelligence and comorbidity with epilepsy. Disturbances in synaptic transmission, including the GABAergic, glutamatergic, and serotonergic systems, are known to be involved in the pathogenesis of this disorder, yet we do not know if there is a common molecular mechanism. As mutations in the GABAergic receptor subunit geneGABRA4 are reported in patients with ASD, we eliminated theGabra4 gene in mice and found that theGabra4 knockout mice showed autistic-like behavior, enhanced ...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
This study uncovers a critical role of KAT8 in cerebral and NSPC development, identifies 9 individuals with KAT8 variants, and links deficient H4K16 acylation directly to intellectual disability, epilepsy, and other developmental anomalies.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
We report familial inheritance of two CNVs that include genes with known involvement in neurodevelopment. These CNVs are found in various combinations among four siblings with autism spectrum disorder, as well as in their neurodevelopmentally normal parents. We describe a 2.4 Mb duplication of 4p12 to 4p11 that includes GABRA4 (OMIM: 137141) and other GABA receptor genes, as well as a 246 kb deletion at 22q11.22 involving the TOP3B gene (OMIM: 603582). The maternally inherited 4p duplication was detected in three siblings, two of whom also had the paternally inherited 22q11.22 deletion. The fourth sibling only had the ...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
(Abstracted from Nat Comm 2019;10:3043) Epidemiologic associations have been made between advanced paternal age and increased offspring risk of autism spectrum disorder (ASD), schizophrenia (SCZ), congenital heart disease (CHD), epilepsy (EPI), and intellectual disability (ID). This association have been often attributed to de novo single nucleotide variants (dnSNVs) that occur 3 to 4 times more often in paternal compared with maternal germ cells.
Source: Obstetrical and Gynecological Survey - Category: OBGYN Tags: GYNECOLOGY: GENETICS Source Type: research
More News: Autism | Brain | Epilepsy | Genetics | Neurology | Pediatrics