Decoding Huntington's disease: a global survey on symptoms and genetic testing practices

Huntington's disease (HD) is a fatal, autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene. While chorea is the hallmark motor symptom, HD presents with diverse psychiatric and cognitive manifestations that usually precede motor onset.

A 10-question online survey was distributed to 130 neurologists and neuro-geneticists from the European Huntington's Disease Network (EHDN) to identify clinical symptoms considered pathognonomic of HD and criteria for genetic testing. Responses from 52 specialists were anonymized and analysed using Microsoft Excel and SPSS 26.

Respondents, averaging 18.4 years of experience, universally identified chorea as indicative of HD, alongside cognitive slowing, irritability, and gait abnormalities. Symptoms like neuropathy, limb weakness, and tremor were deemed inconsistent with HD. Notably, 19% of experts reported that ancillary symptoms would not deter them from recommending testing if a primary HD symptom was present. Without a family history, only chorea with or without additional symptoms was deemed sufficient for testing.

The findings highlight the complexity of diagnosing HD, the importance of considering subtle psychiatric and cognitive symptoms, and the need for comprehensive patient counselling. Advances in genetic testing and therapeutic trials targeting the molecular root of HD offer hope for curative treatments.

This study underscores the growing recognition of HD's pleiotropy, the ethical considerations in testing, and the importance of clinical vigilance as patients may often first present in a non-neurological setting.