disorder
Neurodevelopmental disorder NDDs were established as a broad disorder category for DSM‑5. A former chapter entitled Disorders usually first diagnosed in infancy, childhood, or adolescence was what they substituted. In the most recent revision of the International Classification of Diseases released by the WHO, ICD‑11, the NDDs further gained recognition by becoming a constituent part of the title of the chapter on psychiatry, Mental, behavioral, or serious neurodevelopmental disorders.
The major categories of neurodevelopmental disorders in DSM-5, their etiological history, and the genetic spectrum hypothesis of neurodevelopmental disorders will be explained subsequently in this article.
NDDs comprise intellectual disability Communication Disorders; Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, Neurodevelopmental Motor Disorders, including Tic Disorders; and Specific Learning Disorders.
ICD‑11 classification of NDDs does not differ much from DSM‑5. Notably, all NDDs in DSM‑5 can include the specifier linked to a known medical or genetic or environmental factor. This specifier provides the clinician with the option of recording etiological factors, for example, fragile X syndrome, and is an indicator of the fact that this category is likely to be revolutionized in the next couple of decades by new information becoming available from genetics research.
Distinguishing ASD from mental retardation
In a series of disorder lectures to the Medical Society of London in 1887, he also reported 10 cases of idiot savants, patients who had remarkable skills in an extremely limited area, like calendar calculating. Though none of these cases were autistic, the majority of them would now meet Criterion B for ASD in DSM‑5 i.e., restricted and repetitive patterns of behavior, interest, or activities. In subsequent publications in papers, Down relied on three decades of clinical experience to suggest a division of mental retardation into congenital, accidental, and a third type that he called developmental.
In the most recent revision of the International Classification of Diseases released by the WHO, ICD‑11, the NDDs further gained recognition by becoming a constituent part of the title of the chapter on psychiatry, Mental, behavioral, neurodevelopmental disorders, exhibited rhythmical. The last occurred in children without the usual physical features of retardation.
These children were among some of those who had grown normally till the stage of second dentition, and then abruptly regressed, lost their desired brightness and speech, inhabited a world of their own, used the third person in speaking, exhibited rhythmical and automatic movements, and reduced responsiveness to all the endearments of friends. Troffer remarks on Down’s striking use of the designation developmental retardation for this category likely to include cases of both early-onset and late-onset regressive autism.
Genetic Classification
Genetic analysis of complex disorder typically takes a route from phenotype to genotype to gene, so-called forward genetics. The majority of disease genes have, nonetheless, been discovered through a method called reverse genetics, i.e., the discovery of a gene through its chromosomal location, without initial knowledge of its protein product or the molecular pathway in which it acts. Advances in methods to produce high volumes of genetic information by genome-wide genotyping have enabled genetic research to more and more on the application of unbiased genome-wide strategies to gene discovery.
This resulted in the idea of reverse phenotyping. In reverse phenotyping, genetic markers serve as drivers, or the source for new definitions of phenotypes, such that phenotypes are classified based on genetic marker information. The aim is to establish phenotypic classifications which are defined by greater proportions of allele-sharing linkage data, or more divergent allele frequency association data, than occur for the conventional diagnosis groups. This genotype-first strategy was beautifully expounded by Steersman as a method of characterizing the subtypes of a latest complex disorder. They characterized a genetic subtype as a gene where recurrent mutations have an excess burden in cases compared to controls.
The hypothesis of a genetic neurodevelopmental continuum
Over the past decade, evidence has been accumulating that childhood neurodevelopmental disorders such as ID, ASD, and ADHD share specific genetic risk alleles, as well as psychiatric disorders, particularly schizophrenia. Copy number variants CNVs associated with ID were significantly enriched in patients with schizophrenia, supporting the view that many additional ID-related variants also confer risk to schizophrenia, but at reduced penetrance.
This has prompted authors to suggest the model of a neurodevelopmental continuum, where neurodevelopmental, such as schizophrenia, are viewed as capturing the varied range of consequences that stem from compromised or aberrant brain development. Therefore, childhood neurodevelopmental disorders ID, ASD, ADHD, genetic alleles, genetic developed and adult psychiatric disorders such as both bipolar and schizophrenia would be more usefully thought of as existing on an etiological and neurodevelopmental continuum, rather than being distinct entities.
The model rests on the newly emerging evidence for common genetic and environmental risk factors and predicts that there are probably shared pathogenic mechanisms. The authors have advanced this model a step further and have introduced the neurodevelopmental gradient hypothesis, where disorders are graded based on the severity of neurodevelopmental impairment.
Neurodevelopmental disorders are linked with lower fecundity. It can be assumed then, that genetic variants responsible for high risk for such ought to be uncommon in the population because of adverse selection. The prevalence of such variants in the population must be a function of that selection pressure and rate of replacement due to new, or de novo mutation. The elevated rate of de novo variants in the majority of latest neurodevelopmental disorders is consistent with this postulation.
Patients with severe, undiagnosed developmental are enriched for deleterious de novo mutations in developmentally significant genes in the Deciphering Developmental Disorders Study. In a big whole-exome sequencing study of 4293 families with members who had developmental disorders and a meta-analysis of data on another 3287 members with the same, the DDDS found 94 genes enriched for harmful de novo mutations. The authors approximated that 42% of the cohort had pathogenic DNMs in coding sequences, and about half impaired gene function, with the rest causing changed function.
Conclusion
The diagnostic category of neurodevelopmental disorders NDDs through DSM-5. We further examine how the evolution of genetics will revolutionize the classification and diagnosis of NDDs. NDDs in DSM-5 include intellectual disability ID, autism spectrum ASD, and attention-deficit/hyperactivity disorder ADHD. Doctors in German-, French-, and English-speaking nations e.g., Weikard, Georget, Esquirol, Down, Asperger, and Kanner have provided phenomenological definitions of these over the 18th and 20th centuries.
These diagnostic entities exhibit significant comorbidity and phenotypic overlap. NDDs are one of the psychiatric nosology chapters most likely to gain from the strategy promoted by the National Institute of Mental Health’s Research Domain Criteria project. Genetic investigations validate the view that ID, ASD, ADHD, schizophrenia, and bipolar are on the neurodevelopmental continuum. Recognition of copy number variants and disrupting gene variants present in ASD for example, CDH8, 16p11.2, and SCN2A prompted the adoption of the genotype-first strategy to delineate individuals at the last stage etiologic level.
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