Still Waiting: A Family’s Journey Through Genetic Uncertainty on World Undiagnosed Day
- Simran Thawani
- May 1
- 4 min read
Every year on World Undiagnosed Day, we honor the stories that don’t yet have answers — the children without a diagnosis, the families navigating a sea of inconclusive reports, and the many professionals walking alongside them in quiet solidarity. One such story is that of a couple whose journey I had the privilege — and emotional challenge — of witnessing.
Their son, now 13 years old, began showing symptoms at the age of 3.5. It started subtly — leg pain, toe walking, episodes of muscle weakness. But what followed was a complex diagnostic odyssey spanning nearly a decade and four different genetic tests. Despite countless efforts, a definitive diagnosis was never reached.
A Timeline of Testing, and the Toll It Took
The journey began in 2016 with a targeted exome sequencing, which revealed an incidental finding unrelated to the child’s symptoms. Parental testing was pursued to assess the relevance of this finding — ultimately, it was not significant. Still, it set the tone: complex, inconclusive, and emotionally taxing.
Later that same year, a whole exome sequencing (WES) identified two VUS (variants of uncertain significance) in the TTN gene, a gene associated with various muscular disorders. Again, parental testing revealed these variants were inherited, making their clinical relevance unclear.
The couple hoped for answers but received only more ambiguity.
A neuromuscular panel followed, uncovering a VUS in the SCN4A gene — but this variant didn’t match the child’s clinical picture. No parental testing was done this time. By now, they had already invested years, energy, and money into a process that seemed increasingly opaque.
They persisted. All recommended non-genetic tests — EEG, MRI, ECG, and EMG/NCS — were completed. In 2020, a research-based whole exome sequencing was performed. It came back negative. A muscle biopsy and Western blot even showed reduced expression of specific muscle proteins, pointing to a likely underlying condition. But without a confirmed genetic diagnosis, even these results could not guide the next steps.
No list of genes analyzed was included in any of the tests, and there was no way to confirm whether the genes encoding the affected proteins had even been looked at.
When Science Fails to Keep Pace with Time
When the couple came to the clinic in 2024, the wife was pregnant again — and desperate for clarity. But there was none. The lack of a confirmed diagnosis in their son meant that no targeted prenatal testing could be offered for the ongoing pregnancy. They were left to choose between an invasive test that might yield no actionable result — or continuing the pregnancy without knowing the affected status.
Meanwhile, I tried everything I could to retrieve old data. I contacted the labs, the clinicians, even the researchers involved in the exome project. But time had eroded access. Commercial labs had shut down services. The research team had disbanded. The raw data from all previous tests was lost.
By this point, the emotional and financial burden had taken its toll. The couple was exhausted. Disillusioned. After nearly a decade of testing, hospitals, reports, and waiting — they chose not to pursue further testing for their son or for the ongoing pregnancy. Their decision, rooted in heartbreak and hard-earned wisdom, was to move forward — not because they had answers, but because they simply couldn't endure more questions.
What This Teaches Us
This case is not rare. It is common. And it raises urgent issues for our healthcare and genetic testing systems:
1. The Importance of Trio Testing
In all the testing done for this child, no full trio-based exome or genome sequencing was ever performed. Testing the child’s DNA alongside both parents could have dramatically improved variant interpretation and potentially shortened this diagnostic odyssey.
2. How Far We've Come
From 2016 to 2025, the field of genetic diagnostics has evolved immensely. Technologies are more sensitive, interpretation pipelines more refined, and databases far more complete. What was undetectable in 2016 might be diagnosable today with a whole genome sequencing — an option we discussed, but which the couple ultimately declined.
3. The Cost of Inaccessibility
When families cannot access raw data from previous tests, they are forced to start from scratch — losing time, money, and trust. Genetic data must be portable, retrievable, and patient-owned.
4. The Psychological Weight of the Unknown
The inability to test their unborn child for the same condition as their son intensified the couple’s anxiety. This isn’t just a genetic challenge — it’s an emotional and ethical one. As professionals, we must acknowledge this trauma and create support systems that address not just the medical, but also the psychological toll of undiagnosed conditions.
This couple’s story is one of resilience and quiet courage. Despite systemic failures, they carried on. Despite emotional fatigue, they showed up. Despite uncertainty, they chose hope.
On this World Undiagnosed Day, let us advocate not just for better science — but for better systems. Systems where data is preserved, trio testing is prioritized, and emotional support is considered as critical as clinical care. And above all, let us never forget that behind every "undiagnosed case" is a family — waiting, worrying, and still hoping for a name.
To all those still waiting: we see you.
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