Huntington disease-like 1

Huntington disease-like 1 (HDL1), also known as HD-like 1 or prion protein gene-associated Huntington disease-like syndrome, is an extremely rare neurodegenerative disorder that closely resembles Huntington disease (HD) but is caused by mutations in the PRNP gene (prion protein gene) on chromosome 20p13, rather than the HTT gene. Specifically, HDL1 is associated with an octapeptide repeat insertion in the PRNP gene. The condition primarily affects the central nervous system and leads to progressive neurological decline. Clinical features of HDL1 include progressive chorea (involuntary movements), personality and behavioral changes, cognitive decline progressing to dementia, psychiatric symptoms, rigidity, and seizures. The disease typically presents in adulthood, usually between the third and fifth decades of life, and follows a progressive course over approximately 1 to 10 years. Brain imaging may show cortical and caudate atrophy, similar to classic Huntington disease. The phenotypic overlap with HD makes genetic testing essential for accurate diagnosis, particularly in individuals who test negative for the HTT CAG repeat expansion. There is currently no cure or disease-modifying treatment for HDL1. Management is supportive and symptomatic, focusing on controlling movement abnormalities, psychiatric symptoms, and maintaining quality of life. Multidisciplinary care involving neurologists, psychiatrists, genetic counselors, and allied health professionals is recommended. Given its autosomal dominant inheritance, genetic counseling is important for affected families to understand recurrence risks and reproductive options.

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