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At 10 months old, my daughter Gabrielle had missed key milestones for gross motor, fine motor, social and communication skills. Following two seizures, Gabrielle had an MRI that showed brain abnormalities. When I was given the MRI results, I crumpled to the ground.

Over the next year, Gabrielle was diagnosed with epilepsy, global developmental delays, and autism spectrum disorder. While our diagnostic journey may have ended there, my husband and I, both physicians, wondered whether there was something deeper behind Gabrielle’s diagnoses. So we were excited when we were referred to a pediatric geneticist who offered Gabrielle whole exome sequencing, which sequences all of the protein-coding regions of the genome, to determine whether there was a genetic cause.


Just before she turned 2 years old, we learned that Gabrielle has a mutation on her CACNA1A gene that is associated with multiple neurological disorders, including neurodevelopmental differences such as developmental delay, cognitive impairment, autism, speech and language disorder, epilepsy, balance and coordination difficulties, migraines and eye movement disorders. We were lucky to get this information so early — or even at all. Many children with CACNA1A gene mutations never find out what is causing their developmental differences. As a board-certified pediatrician and the mother of a child with a rare disease, I believe the medical system is failing the rare disease community by vastly underdiagnosing genetic disorders.

Most families are offered either no genetic testing at all or only limited panels that cannot find most genetic mutations. The reasons for this are manifold, but include:

  1. Pediatricians, who aren’t trained to investigate genetic causes for conditions like developmental delay or epilepsy, often conclude these are diagnoses rather than symptoms. But research suggests that genetic factors are responsible for up to 40 percent of developmental disability cases, such as global developmental delay and intellectually disability, and that 40% to 70% of unexplained epilepsies have a genetic cause.
  2. The American Academy of Pediatrics’ 2014 clinical report “Comprehensive Evaluation of the Child with Intellectual Disability or Global Developmental Delays” recommends chromosome microarray as a first-tier diagnostic test. Significant changes in genetic diagnosis in the last several years have made this 2014 clinical report out-of-date. In the report, it mentions that whole genome sequencing offers promise but there are also challenges that need to be addressed. In the last nine years, these challenges have not been addressed, nor have the guidelines been updated. Given the rapidly evolving field of genetics, whole exome and whole genome sequencing have become more accessible and affordable, and have a higher diagnostic yield than targeted testing. These tests save families valuable time, helping them get to a diagnosis faster. For families who are witnessing degenerative symptoms, this timing is of the essence.
  3. Pediatricians have been taught that ordering genetic testing is beneficial only if there is a specific treatment available for the suspected mutation. This approach denies families the opportunity to know why a child is experiencing developmental delays, connect with other families with the same diagnosis, identify appropriate supportive care, pursue off-label treatments, and participate in research that may help find new treatments.

Gabrielle’s genetic diagnosis changed everything for our family. Through the CACNA1A Foundation, we have formed supportive relationships with other families affected by CACNA1A-related disorders, some of whom have the same variant as Gabrielle. We learned about intensive therapy that has helped Gabrielle communicate with us for the first time, found doctors willing to pursue off-label treatments that have helped control her seizures, and were connected directly to researchers who are using her case as real-world evidence to better understand this genetic disorder.


Through the foundation, we’ve also been able to participate in a natural history study, which collects real-world data from patients to understand disease progression over time. My family hopes that the study will provide researchers and the pharmaceutical industry with enough data to pursue the development of new treatments or even a cure for Gabrielle and others like her. One recent development that gave us hope: On Feb. 28, the FDA approved a new treatment for a rare disease, Friedreich’s ataxia. The approval was based partially on data from a natural history study, proving how critical these studies are to accelerate the development and approval of new treatments for rare diseases.

Gabrielle’s diagnosis has also changed how I practice medicine. The protocol I now follow with my own patients is not something I learned in medical school — there is no AAP guidance for it. I use what I learned from my personal journey with Gabrielle. I now advocate for genetic testing for my patients who show developmental delays, autism, or unexplained epilepsy. If the AAP had a practice guideline recommending specific genetic testing to pursue for neurodevelopmental disorders, it would benefit thousands of patients and families. This would start to make specific genetic testing the autopilot next step for practicing pediatricians and residents in training, and it would help make the case for insurance companies to cover genetic tests more widely.

Given the benefits I have seen for my family and my patients, I urge the AAP to develop new guidelines that are aligned with the 2021 American College of Medical Genetics and Genomics practice guidelines. These recommend whole exome/genome sequencing as a first or second-tier test for pediatric patients with congenital anomalies, developmental delay, or intellectual disability. I also believe that the American Board of Pediatrics should include whole exome sequencing in its board content so that current and future pediatricians are trained on when and how to offer it.

I know these systemic changes can take time. Until then, I urge my fellow pediatricians to learn more about genetic testing and to offer and advocate for whole exome sequencing for your patients with developmental delays. Our job is to fight for the health of each of our patients now, and we can’t do that effectively without evolving our practice to embrace advances in genetic testing.

Deborah Ondrasik is a board-certified pediatrician in Massachusetts and the mother to three children. She is an active volunteer with the CACNA1A Foundation, whose mission is to find effective treatments and a cure for CACNA1A-related disorders.

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