Wales DRPLA cluster prompts questions, care path and trials

A cluster of Dentatorubral-pallidoluysian atrophy, DRPLA, has drawn attention in south Wales as researchers map how common the inherited neurological disorder is beyond its traditional associations with Japan. DRPLA is progressive and currently has no approved treatment or cure. A 2007 study found a relatively high prevalence of the condition in Wales, prompting ongoing clinical and patient-led work to understand who is affected and how the disease progresses.

Rachel Cowley learned of DRPLA through her daughter Jessica, who was diagnosed in May after years of seizures. Jessica, now 20, began seizing at age 10 and, by her early teens, her legs gave way and she lost the ability to walk or speak. She now relies on a wheelchair and is non-verbal. "I hope when the time comes it is quick," Cowley said, "but I just don’t think it’s going to be." The case exemplifies the uncertainty families face when symptoms worsen and doctors struggle to diagnose a rare condition.

DRPLA can include memory loss, personality changes, impaired movement, muscle spasms, seizures and psychiatric disturbances, and is caused by an expansion in the ATN1 gene; each child has a 50% chance of inheriting the defect if one parent carries it. Dr Mark Wardle, a consultant neurologist who authored the 2007 study, said there are common founders in south Wales that have produced a cluster of patients in their 20s and 30s, suggesting that the accumulation of generations can lead to more cases over time.

Cowley joined a Facebook group called DRPLA in south Wales, which now has more than 100 members. She said discovering others in the area facing similar challenges provided a sense of connection. Among the group is Zoe Hoes, who adopted her daughter Gabriella after a positive test in the family; the private genetic test that confirmed Gabriella’s condition cost thousands of pounds, a barrier not affordable for many families. Hoes described the moment of diagnosis as devastating and said there is no treatment or cure at present.

Hoes said families need access to testing at younger ages to help plan for their children’s futures, but Dr Wardle emphasized that testing minors raises moral and ethical questions because some people may not be mature enough to understand the consequences of such knowledge. He noted that early diagnosis could alter care decisions, but there is no disease-modifying therapy available yet, so early access would depend on future treatment approvals.

Researchers are watching developments in the United States where a CureDRPLA trial is testing a treatment in two patients; early results have shown some improvement in a teenage boy’s ability to walk a few steps and gain some hand movement and clearer speech, while another patient at a later stage showed less dramatic gains. Dr Silvia Prades of CureDRPLA, a charity-affiliated research manager, cautioned that results vary and that early signs are encouraging but not definitive. She stressed that testing decisions are personal, with some families feeling empowered by knowledge, others overwhelmed by it. She also noted that higher prevalence in Wales could reflect more people seeking genetic testing and a shift in stigma, though other factors might be at play.

Prades said there could be multiple factors explaining the apparent concentration in south Wales, including improved access to genetic testing and increased awareness. She noted that families engaging with researchers in recent times may be responding to the visible symptoms and to better information, and that the stigma around genetic conditions is diminishing.

For families, the news offers cautious optimism amid ongoing questions about treatment, testing, and long-term care. Dr Wardle and researchers advocate broader awareness and better access to neurological services and genetic testing to push the field forward, while recognizing the ethical and logistical challenges. In Wales, the DRPLA cluster remains a mix of personal hardship and scientific curiosity, with patients and clinicians pursuing a path toward clarity and, perhaps someday, effective therapies.