Category : Genetics
Mind the Gap: Why We’re Trading “Wait and See” for “Test and Know”
In the high-pressure environment of a tertiary care hospital, clinical practice often feels like a race against time. We see patients through brief snapshots—a single seizure, a delay in speech, or a repetitive movement. However, for a family living with autism spectrum disorder (ASD), life is not simply a snapshot; it is a long, often exhausting narrative. As a clinical geneticist, my role is to pause that narrative and delve beneath the surface. While the world observes World Autism Awareness Day on April 2nd, we in the clinic observe it every day. For us, this day serves as a reminder that “autism” is not a destination but a starting point for a deeper biological investigation.
The Fragmented Journey: From Observation to Inquiry
The journey often begins with a parent’s intuition. Parents may notice a child who doesn’t meet their mother’s gaze, a toddler who focuses intently on the spinning wheels of a toy car instead of the game itself, or a preschooler who remains silent while peers chatter. Initially, these children are evaluated by paediatricians, then neurologists, and later speech therapists. Each specialist addresses a piece of the puzzle: the neurologist treats associated epilepsy, while the therapist works on social skills. For many years, these cases remained classified as “idiopathic”—medical shorthand for “we don’t know the cause.”
The “Aha!” moment in the genetics outpatient department (OPD) occurs when we stop viewing these behaviours as isolated traits and begin to see them as signals of a neurodevelopmental blueprint.
The Architecture of the Spectrum
We use the term “spectrum” because no two individuals with autism are identical. Genetics helps explain why. We now understand that ASD is polygenic and multifactorial.
- The Power of “De Novo” Mutations”
In many families with no history of neurodevelopmental issues, a child is born with ASD due to de novo mutations—genetic “typos” that occur spontaneously in the germ cells (egg or sperm) or shortly after conception. These mutations do not get passed down in the traditional sense, but they can significantly alter the trajectory of the child’s brain development. - Copy Number Variations (CNVs)
Sometimes, the issue isn’t a single “typo” but rather a missing or extra “page” in the genetic instruction manual. Through Chromosomal Microarray (CMA), we can detect deletions or duplications of genetic material. For example, a deletion at the 15q11-q13 locus is a well-known genetic area associated with autism, language delays, and distinct physical features. - Syndromic vs. Non-Syndromic Autism
In about 10-15% of cases, autism is part of a larger syndrome:- Fragile X Syndrome: The most common inherited cause of intellectual disability and autism in boys.
- Tuberous Sclerosis: This condition involves benign tumours that grow in the brain and other organs, often manifesting as autism.
- Rett Syndrome: Primarily affecting girls, this condition leads to a loss of purposeful hand skills and social withdrawal.
The Weight of the “Why”: Why Genetic Testing Matters?
A common misconception is that a genetic diagnosis is “bad news.” On the contrary, for many parents, a molecular diagnosis can provide a sense of liberation.
“It wasn’t my parenting. It wasn’t the vaccine. It wasn’t a lack of vitamin D. It was a change in the SHANK3 gene, or in other words, a genetic cause.”
Beyond emotional relief, a definitive diagnosis offers a clinical roadmap:
- Precision Medicine: While still in its early stages, identifying specific pathways (like the mTOR pathway) may someday lead to targeted clinical trials.
- Proactive Surveillance: If a genetic change is known to be associated with kidney or heart issues, we do not wait for symptoms to appear; we actively screen for them.
- Empowered Planning: For parents considering more children, understanding whether a mutation is de novo (low recurrence risk) or inherited (higher risk) is crucial for informed reproductive choices.
The Indian Landscape: Challenges and Progress
In India, we face a unique “double burden.” Our large population, combined with a high rate of consanguinity in certain regions, increases the prevalence of recessive genetic disorders. Additionally, significant hurdles exist:
- The Cost Barrier: Advanced tests like Whole Exome Sequencing (WES) remain expensive for the average family, although prices are beginning to decline.
- Cultural Stigma: Neurodivergence is often hidden due to fears of social exclusion or concerns over marriage prospects for siblings.
- The “Wait and See” Approach: Many families are told their child is simply a “late bloomer,” which can lead to missed opportunities for early intervention.
However, strengths are emerging. India is becoming a hub for genomic research, and our National Policy for Rare Diseases represents a step toward recognising that neurodevelopmental disorders require state-supported diagnostic infrastructure.
Conclusion: Beyond Awareness to Acceptance:
World Autism Awareness Day is a call to action. It urges us to shift our perspective from seeing autism as a “behavioural problem” to recognising it as a biological variation. As clinicians, our task is to provide the “Why.” As a society, we must tackle the “So what?”—ensuring we promote understanding, acceptance, and support for individuals with autism and their families.
Regards,
Dr. Varun Venkat Raghavan MS,
Associate Professor and Head,
Department of Medical Genetics,
JSS Medical College and Hospital,
Mysuru, India.