PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review
Anxo Manuel Minguillón Pereiro,
Beatriz Quintáns Castro,
Alberto Ouro Villasante,
José Manuel Aldrey Vázquez,
Julia Cortés Hernández,
Marta Aramburu-Núñez,
Manuel Arias Gómez,
Isabel Jiménez Martín,
Tomás Sobrino,
Juan Manuel Pías-Peleteiro
Affiliations
Anxo Manuel Minguillón Pereiro
Servicio de Neurología, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana, 15706 Santiago de Compostela, Spain
Beatriz Quintáns Castro
Fundación Pública Galega de Medicina Xenómica, Hospital Clínico Universitario Santiago de Compostela, Rúa da Choupana, 15706 Santiago de Compostela, Spain
Alberto Ouro Villasante
NeuroAging Laboratory (NEURAL) Group, Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain
José Manuel Aldrey Vázquez
Servicio de Neurología, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana, 15706 Santiago de Compostela, Spain
Julia Cortés Hernández
Servicio de Medicina Nuclear, Sección de Sistema Nervioso Central, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana, 15706 Santiago de Compostela, Spain
Marta Aramburu-Núñez
NeuroAging Laboratory (NEURAL) Group, Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain
Manuel Arias Gómez
Servicio de Neurología, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana, 15706 Santiago de Compostela, Spain
Isabel Jiménez Martín
Unidad de Neuropsicologia Clínica, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana, 15706 Santiago de Compostela, Spain
Tomás Sobrino
NeuroAging Laboratory (NEURAL) Group, Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain
Juan Manuel Pías-Peleteiro
Servicio de Neurología, Hospital Clínico Universitario Santiago de Compostela, Travesía de Choupana, 15706 Santiago de Compostela, Spain
Background: Monogenic Alzheimer’s disease (AD) has severe health and socioeconomic repercussions. Its rarest cause is presenilin 2 (PSEN2) gene mutations. We present two new cases with presumed PSEN2-AD with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients. Methods: Women aged 69 and 62 years at clinical onset, marked by prominent behavioral and language dysfunction, progressing to severe dementia within three years were included. The complete study is depicted. In addition, a systematic review of the PSEN2-AD was performed. Results: Neuroimaging revealed pronounced frontal white matter hyperintensities (WMH) and frontotemporal atrophy/hypometabolism. The genetic study unveiled PSEN2 variants: c.772G>A (p.Ala258Thr) and c.1073-2_1073-1del. Both cerebrospinal fluid (CSF) and experimental blood biomarkers shouldered AD etiology. Conclusions: Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related to myelin disruption induced by amyloid accumulation.
