Genotype-phenotype correlation of neurodevelopmental disorders in patients with dystrophinopathies

TL;DR

This study explores how genetic variations in dystrophinopathies relate to neurodevelopmental disorders like ADHD, OCD, and ASD.

Contribution

The study identifies a genotype-phenotype correlation between DMD mutations and neurodevelopmental symptoms, particularly involving cerebral dystrophin isoforms.

Findings

ASD and OCD symptoms are linked to DMD genotypes affecting cerebral dystrophin isoforms.

Over half of participants showed ADHD symptoms, with cerebral isoform disruption in 52%.

CARS scores and OCD prevalence correlate with the position of DMD variants.

Abstract

Neurodevelopmental disorders are frequently and heterogeneously diagnosed among patients with dystrophinopathies. The authors aimed to evaluate how the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), Obsessive-Compulsive Disorder (OCD), or Autism Spectrum Disorder (ASD), and genotype are related to DMD genotype.

In an observational cross-sectional study, standardized instruments were applied to 50 participants and their caregivers, mainly from a reference center for rare diseases in Southern Brazil (n = 38) or other Brazilian centers (n = 12). Participants were divided according to genotype and affected dystrophin isoforms.

The overall diagnostic rate of symptoms of ASD was 34 %, similar to OCD (35.5 %), with half of the participants (51.4 %) having symptoms compatible with ADHD. Cerebral isoforms were affected in more than half of the participants (52 %). Symptoms compatible with ASD and OCD, and Childhood Autism Rating Scale (CARS) scores were associated with genotype and impairment of cerebral isoforms of dystrophin.

The prevalence of symptoms compatible with ASD (and higher CARS scores) and OCD among patients with dystrophinopathies are related to the position of the causal variant in DMD and the consequent involvement of cerebral isoforms, indicating an important genotype-phenotype correlation. The diagnosis of a patient with a genotype that affects these isoforms indicates the need for neuropsychological assessment and multidisciplinary follow-up.

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