Fatal Familial Insomnia

Fatal familial insomnia is an autosomal dominant prion disease caused by mutations in the PRNP gene. Pathophysiology involves selective thalamic neuronal loss leading to progressive insomnia, autonomic dysfunction, and cognitive decline. Clinical features include sleep disturbance, autonomic instability, motor signs, and dementia. Diagnosis relies on clinical features, polysomnography, genetic testing, and MRI. Management is supportive; the disease is universally fatal, typically within 12–18 months of onset.