Parental Traits Linked to Severity of Neurodevelopmental Disorders

Key Points:

• Spectrum Disorders are Early-onset conditions affecting daily functioning (e.g., ASD, ADHD).
• Parents with similar traits increase disorder risk in children.
• Multiple mutations interact, making prediction difficult.
• Parental traits help improve diagnosis and treatment.

Neurodevelopmental disorders are a heterogeneous group of disorders that often lie on a spectrum. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM: 5) defines Neurodevelopmental disorders as “a group of conditions with onset in the developmental period. The disorders typically manifest early in development, often before the child enters grade school, and are characterized by developmental deficits that produce impairments of personal, social, academic, or occupational functioning. These include conditions like Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), Specific Learning Disorders, Intellectual Developmental Disorder, Tic Disorders, to name a few.

A recent research by Santhosh Girirajan, co-authored by 42 others, titled as “Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants has been drawing large attention in the field of neuroscience. This study, published in the American Journal of Human Genetics, revealed significant details about the development of neurodevelopmental disorders. The researchers examined over 97,000 families aiming to understand the influence of parental traits in the development of neurodevelopmental and psychiatric conditions and its effect on the severity and prevalence of these disorders in their children.

The researchers assessed parents and their children for symptoms of the different disorders, as well as known genetic mutations that can cause them. Their findings demonstrated that parents tend to choose partners who have the same or similar conditions, which increases the prevalence and, perhaps, severity of the disorder in their offspring, This can be explained by a phenomenon called Assortative Mating. As said by one of the authors, “whether it’s consciously or unconsciously, people with similar features preferentially find each other as partners. Although there could be other explanations, we see this in our data and that is probably what is leading to what we are seeing in the families that we studied.”

In this context, Girirajan explained that even genetic similarity between spouses increases the possibility that their children would inherit and display these traits. For example, the study discovered that when neither parent had anxiety, around 12.6% of their male offspring had anxiety. However, this number soared to 25.7% when one of the parents reported anxiety, and to 33.8% when both parents reported anxiety. This increase in prevalence means that the severity of these traits in children is increasing, as more severe features are easier to identify.

According to the author, “most neurodevelopmental disorders are genetically complex, meaning that they aren’t caused by a single gene. This makes it hard to trace the exact genetic underpinnings of a disorder in an individual and even harder to predict how the disorder will play out in affected children.” As per the “multi-hit-model”, the prognosis is determined by the combination of mutations they inherit and how they interact with each other throughout development. One such mutation that has been considered as a risk factor for various neurodevelopmental disorders is a deletion of a small segment of chromosome 16. The symptoms can manifest in forms like seizures, features of schizophrenia, depression and anxiety, as well as addiction-related characteristics.

This research emphasises that understanding how both parents contribute to their child’s diagnosis might help with genetic counseling and the formulation of therapeutic interventions for children affected by these conditions. By examining the traits in both parents, the researchers would be able to more accurately anticipate the progression of the condition in their offspring than would be achievable with genetic screening alone. They may also use this information to attempt to find new mutations that are responsible for these traits.

The research has been supported by grants from the US National Institutes of Health, the South Carolina Department of Disabilities and Special Needs, and the Italian Ministry of Health-Ricerca Corrente.