Repeat Expansion Disorders
Repeat expansion disorders (REDs) are genetic conditions where a repeated DNA sequence grows longer from one generation to the next. These repeating patterns occur naturally in our genes, but when they expand beyond a certain threshold, they can disrupt normal gene function and lead to a range of problems at the cell level.
REDs can affect many parts of the body, including the brain, muscles, nerves, heart and eyes. While some of these conditions are well known, they remain widely underdiagnosed, because standard genetic tests often lack the resolution to detect or accurately measure these expansions.
How Rare Are REDs?
Each RED is rare, but as a group they affect more people than is commonly realized. Current estimates suggest about 1 in 3,000 people worldwide has a RED, which translates to more than 25 million individuals. The true number may be significantly higher: emerging genomic research indicates that two to three times as many people could be affected, with most remaining undiagnosed.
There are several reasons REDs can evade diagnosis. Repeat lengths vary even among family members. Symptoms can emerge at any age and may involve multiple parts of the body, often resembling other conditions. And even when a diagnosis is correct, treatment options have been limited. With new genetic therapies now in development, accurate diagnosis has become far more important.
Some Examples of REDs
More than 40 types of REDs have been identified to date, and more are likely to emerge. Below are the are the most recognized:
Myotonic Dystrophy Type 1 (DM1)
Multisystem disorder affecting muscle, heart, GI tract, endocrine function, sleep and cognition.
Fragile X Syndrome (FXS)
Leading inherited cause of intellectual disability.
Huntington’s Disease (HD)
Fatal neurodegenerative disorder that impairs movement and cognition.
C9orf72-Related ALS, Frontotemporal Dementia (FTD)
Most common genetic cause of ALS and FTD.
Spinocerebellar Ataxias (SCA1, SCA2, SCA3, SCA6)
Progressive disorders affecting balance, coordination and motor control.
Friedreich’s Ataxia (FRDA)
Neurodegenerative and cardiac involvement.
Fuchs Endothelial Corneal Dystrophy (FECD) — Repeat Expansion–Associated
Vision loss from corneal endothelial failure.
Other REDs include FXTAS, Kennedy’s Disease, DRPLA, OPDM, CANVAS syndrome, OPMD (repeat-linked variants) and multiple forms of familial adult myoclonic epilepsy.
Why Testing for REDs Matters Now
As recently as the mid-2010s, few companies were pursuing treatments for repeat expansion disorders, and diagnosis rarely changed the course of care. Today, the landscape looks very different. Gene and RNA-targeted therapies are advancing through clinical trials, reliable testing is available for many common REDs, and identifying patients has become critical to moving new treatments forward.
For the first time, a diagnosis can connect families with emerging therapies, informed care and a clearer path forward.
