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Agrammatic Primary Progressive Aphasia due to GNR Mutation: a Case Report

RESUMO

Case Report
Male, 70 years old, caucasian, aircraft mechanic and 11 years of schooling. Patient sought care for behavioral and speech changes that had been progressing for one year. Patient was recently sadder, quieter, with decreased social interaction and functional decline. He'd previously no neurological symptoms. His mother died at the age 86 due to dementia without specific diagnosis. His older brother is diagnosed with cortico-basal syndrome and his younger brother has no diagnosis but he has similar symptoms to the patient.

Neuropsychological assessment was notable for significant deficits in the Boston Naming Test (-3.8 SD), MOCA test (7/30), along with impaired comprehension of complex sentences, non fluent speech and altered memory, executive function and attention. Brain MRI showed atrophy especially in the left frontal lobe. A genetic investigation found the GRN T272fs mutation (exon 8, c.813_816del), establishing a genetically confirmed case of non-fluent variant frontotemporal dementia (nfvFTD).

Discussion
Frontotemporal dementia (FTD) is a clinical and pathologically heterogeneous syndrome characterized by behavioral, language and executive abnormalities. The spectrum of presentation includes behavioral variant frontotemporal dementia (bvFTD), non-fluent variant primary progressive aphasia (nfvPPA) and semantic variant primary progressive aphasia (svPPA). Unlike the clinical syndrome, the term frontotemporal lobar degeneration (FTLD) is reserved to describe pathological changes of the disease that encompasses the syndrome. So FTD is characterized by a disorder with distinct clinical phenotypes that can coexist and are associated with multiple neuropathological substrates.

NfvPPA is characterized by degeneration of frontal language networks in the brain. It usually manifests in late middle age with minor difficulties with speech but with preserved executive and cognitive functions that, with disease progression, are also impaired.

In etiological terms, it should be noted that mutations in MAPT, C9ORF72 and GRN are the main causes of FTLD, accounting for 30% of the cases. Besides, the most common GRN mutation is T272fs, with a known founder effect in Italy, where the patient’s family is descended.

Final Comments
PPA is an uncommon and underdiagnosed disease often misdiagnosed with Alzheimer's. It's important to highlight that genetic investigation has a main role to confirm diagnosis, allowing better therapeutic approach and even genetic counseling.

Palavras Chave

Primary Progressive Aphasia (PPA), Frontotemporal dementia (FTD), Mutation