Dados do Trabalho

Título

Clinical Variability in a large Gerstmann-Sträussler-Scheinker (p.P102L) kindred from Brazilian Northeast

Resumo

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare autosomal dominant hereditary prion disease caused by a mutation at codon 102 at PRNP protein gene. The disease has high penetrance, and symptoms may vary among affected individuals. The most common presentations are ataxia, dementia, spasticity, nystagmus, and behavioral abnormalities.
This study describes the phenotypical variability within kindred from Bahia state (Brazilian northeast). We used neurologic examination to map clinical symptoms and Addenbrooke's Cognitive Examination-Revised to assess cognition. We used clinical history and genetic panels to map 26 affected individuals, 7 of whom are still alive. In our cohort, we have individuals in different stages of the disease, ranging from pre-symptomatic to bedridden. We also identified 28 individuals at risk of having the mutation who declined genetic testing or could not be tested yet.
The age of onset was between the 3rd and 5th decade of life. Some individuals might have started even earlier if we considered their history of neuropsychiatric symptoms. Gait abnormalities, broad base, and unsteadiness were the first signal observed in all the patients evaluated. During disease progression, ataxia and spasticity become prominent. The Babinski sign is present very early in those patients. On the other hand, cognitive symptoms occurred much later in disease evolution. All the deceased individuals presented ataxia at some moment in their disease progression, along with spasticity and loss of ambulation.
Neurosensorial deafness was observed in 2 out of 7 alive individuals and reported in five other deceased individuals, contrasting with other cohorts in which deafness was reported in less than 2% of individuals. MRI was normal in most patients; some presented mild cerebellar atrophy later in the disease. The causes of death were infection, complications related to neurodegeneration and immobility, and suicide.
Since its first description in 1992, much has been studied in prion protein and its related diseases. Studies of natural history are important to a better understanding of disease progression. They may play an important role in knowing other neurodegenerative disorders with similar progression patterns and pathophysiological substrates. Therefore, there is still much to be investigated in this field. Genetic counseling is very important to reduce the number of affected individuals in the family.