Objective: To describe a patient with early-onset atypical parkinsonism that evolved to a classic CBD without dementia, associated to a c.2092G>A MAPT mutation

Background: Although certain microtubule-associated protein tau (MAPT) gene haplotypes are considered important risk factor for the development of CBD, mutations in the MAPT gene are commonly associated with frontotemporal dementia (FTD) spectrum syndromes. Moreover, genetic phenocopies of atypical parkinsonism have linked MAPT gene mutations to Progressive Supranuclear Palsy (PSP) but not to CBD (1), being rare CBD cases associated with MAPT gene mutations (2)

We present the case of a patient with early-onset atypical parkinsonism (<40 years), with a CBD phenotype associated with a c.2092G>A mutation in the MAPT gene.

Method: A 47-year-old patient consulted for 10 years evolution clumsiness an rigidity of the right hand, exacerbated in the last 3 years. On examination, a right akinetic-rigid syndrome was detected with predominant involvement of the right hand and partial response in the levodopa test. Treatment with dopaminergic medication was started, without response to high doses of L-Dopa (1000 mg/day) and dopamine agonists (pramipexole 2.1 mg/day). Parkinsonian symptoms progressed over time, adding dysarthria, bradilalia, lower extremity involvement right and extension to the left hemibody. No cognitive impairment was perceived.

Results: Brain MRI: without alterations. SPECT with DAT-Scan: involvement of the nigrostriatal pathway. Laboratory tests: normal, including copper and ceruloplasmin.

FDG-PET: hypometabolism of the left thalamus, of both putamens, more marked in the posterior region and especially of the left. Hypometabolic area in the left superior parietal cortex and in the left pre- and postcentral gyrus, in the left superior temporal gyrus, and in the left frontal supplementary motor area with respect to the contralateral hemisphere. Genetic study: LRRK2 and GBA, negative. Mutation in the MAPT gene c.2092G>A p.(Val698lle), previously described in association with Primary Progressive Aphasia (3)

A genetic study was carried out on the parents, detecting the same mutation in the patient’s mother, who was asymptomatic.

Conclusion: MAPT gene mutations can be associated with classic CBD phenotype

Genetic testing should be considered in patients with early-onset atypical parkinsonism

References: 1- Stamelou M, Quinn NP, Bhatia KP. “Atypical” atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy-a diagnostic guide. Mov Disord. 2013 Aug;28(9):1184-99
2 – Ahmed S, Fairen MD, Sabir MS, Pastor P, Ding J, Ispierto L, Butala A, Morris CM, Schulte C, Gasser T, Jabbari E, Pletnikova O, Morris HR, Troncoso J, Gelpi E, Pantelyat A, Scholz SW. MAPT p.V363I mutation: A rare cause of corticobasal degeneration. Neurol Genet. 2019 Jun 25;5(4):e347
3 – Anfossi M, Bernardi L, Gallo M, Geracitano S, Colao R, Puccio G, Curcio SA, Frangipane F, Mirabelli M, Tomaino C, Smirne N, Maletta R, Bruni AC. MAPT V363I variation in a sporadic case of frontotemporal dementia: variable penetrant mutation or rare polymorphism? Alzheimer Dis Assoc Disord. 2011 Jan-Mar;25(1):96-9

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-onset-cortico-basal-degeneration-cbd-due-to-a-c-2092ga-mapt-mutation/