Neurobehavioral Profiles and Clinical Consequences of MYT1L-Related Neurodevelopmental Disorder: Insights From the Brain Gene Registry

19/10/2026

AI Summary

MYT1L-NDD is a rare autosomal dominant syndrome with intellectual disability, global developmental delay, autism symptoms, and obesity.
Prospective RNAP-based testing showed pronounced nonverbal cognitive and adaptive deficits, notably in motor skills, communication, and daily living.
High rates of autism, ADHD, behavioural conduct problems, oppositional defiance, anxiety; EHRs report speech disorders, GI issues, and obesity; common medications include alpha-2 agonists.

TL;DR (AI Generated)

MYT1L-Related Neurodevelopmental Disorder (MYT1L-NDD) is a rare autosomal dominant syndrome characterized by intellectual disability, global developmental delay, autism, and obesity.

Here, we present an exploratory analysis of data from 25 individuals with MYT1L-NDD enrolled in the Brain Gene Registry (BGR), a national platform integrating genetic, neurobehavioral, and clinical data.

Findings expand our understanding of MYT1L-NDD phenotypes in a quantitative and systematic manner and support the value of registry-based approaches for understanding rare neurodevelopmental disorders.

Basic summary

Am J Med Genet A. 2026 Oct 19. doi: 10.1002/ajmg.a.70321. Online ahead of print.

ABSTRACT

MYT1L-Related Neurodevelopmental Disorder (MYT1L-NDD) is a rare autosomal dominant syndrome characterized by intellectual disability, global developmental delay, autism, and obesity. Despite growing recognition, prospective and systematic clinical phenotyping remains limited. Here, we present an exploratory analysis of data from 25 individuals with MYT1L-NDD enrolled in the Brain Gene Registry (BGR), a national platform integrating genetic, neurobehavioral, and clinical data. Neurobehavioral assessments were conducted using the Rapid Neurobehavioral Assessment Protocol (RNAP), including virtual adaptations of the Shipley, Developmental Profile-4, ASEBA Child Behavior Checklist, and Vineland-3. Diagnostic and medication data were extracted from structured electronic health records (EHR). MYT1L-NDD participants were compared to the broader BGR cohort. MYT1L-NDD participants exhibited pronounced impairments in nonverbal cognition and adaptive functioning, particularly in motor tasks, communication, and daily living skills. Behavioral assessments revealed elevated rates of autism symptoms, ADHD symptoms, behavioral conduct problems, oppositional defiance, and anxiety. EHR diagnosis data were available for 10 MYT1L-NDD participants. It showed frequent diagnoses of developmental delays, speech and language disorders, intellectual disability, gastrointestinal problems, and obesity. Medication data on five participants indicated common prescription of alpha-2 adrenergic agonists and laxatives. This study provides the first prospective, multi-source characterization of MYT1L-NDD. Findings expand our understanding of MYT1L-NDD phenotypes in a quantitative and systematic manner and support the value of registry-based approaches for understanding rare neurodevelopmental disorders. Larger, longitudinal, age-stratified studies are needed to further define MYT1L-NDD natural history and inform clinical care.

PMID:42894947 | DOI:10.1002/ajmg.a.70321

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