CASE REPORT Atypical presentation of a novel Presenilin 1 R377W mutation: sporadic, late-onset Alzheimer disease with epilepsy and frontotemporal atrophy Barbara Borroni • Andrea Pilotto • Cristian Bonvicini • Silvana Archetti • Antonella Alberici • Andrea Lupi • Massimo Gennarelli • Alessandro Padovani Received: 22 February 2011 / Accepted: 14 July 2011 Ó Springer-Verlag 2011 Abstract Mutations within Presenilin 1 (PSEN1) repre- sent the most common cause of monogenic Alzheimer Disease (AD). The clinical phenotype is highly variable, even if early onset disease with an autosomal dominant pattern of inheritance and presenting memory deficits usually occur. In the present work, we described the case of a late-onset AD patient, without any positive family history for dementia, and associated with seizures and behavioural symptoms. Structural and functional neuroimaging showed frontotemporal changes without posterior biparietal brain abnormalities. Cerebrospinal analysis was consistent with AD pattern, with decreased Ab42 and increased Tau and phospho-Tau. A novel pathogenetic mutation within PSEN1 gene was detected within exon 8, leading to a substitution from arginine to tryptophan (AGG [ TGG: R377W), affecting a splice junction and protein function. The case herein reported further confirms the heterogeneity of PSEN1 mutations and the need to take into account genetic screening in those cases with atypical presentation. Keywords Presenilin 1 Á Mutation Á Alzheimer disease Á Genetics Á Frontotemporal Introduction Mutations within Presenilin 1 and 2 (PSEN1, PSEN2) and Amyloid Precursor Protein (APP) have been associated with genetic forms of Alzheimer Disease (AD). PSEN1 represents the most common cause of monogenic AD and more than 180 mutations have been identified so far (http://www.molgen.ua.ac.be/admutations). The phenotype of PSEN1 mutations is highly variable [1]; however, early memory impairment is the most common presenting symptom. Atypical features, including seizures, pyramidal signs up to spastic paraparesis, parkinsonism and myoclo- nus may be variably associated with dementia. In most of the cases an autosomal dominant pattern of inheritance is recognised and presenile onset usually occurs [1]. In the present work, we described a novel PSEN1 mutation, namely R377W, in a late-onset AD patient, without any positive family history for dementia, and associated with epilepsy and frontal atrophy. Case report A 68-year-old man was admitted to the Centre for Neurodegenerative Disorders, University of Brescia, Italy, presenting progressive cognitive impairment associated with apathy since the last 2 years. At the age of 60 years, he was diagnosed as having epilepsy, and seizures were under pharmacological control B. Borroni (&) Á A. Pilotto Á A. Alberici Á A. Padovani Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Piazza Spedali Civili 1, 25125 Brescia, Italy e-mail: bborroni@inwind.it C. Bonvicini Á M. Gennarelli Genetic Unit, IRCCS San Giovanni di Dio, Brescia, Italy S. Archetti Laboratories of Biotechnology, Brescia Hospital, Brescia, Italy A. Lupi Nuclear Medicine Unit, Ospedale ‘‘S. Bortolo’’, Vicenza, Italy M. Gennarelli Department of Biomedical Sciences and Biotechnologies, Biology and Genetics Division, University School of Medicine, Brescia, Italy 123 Neurol Sci DOI 10.1007/s10072-011-0714-1