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Brain structural abnormalities and cognitive changes in a patient with 17q21.31 microduplication and early onset dementia: a case report

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Abstract

Objectives

We describe brain structural damage and cognitive profile evolution of an adult patient with 17q21.31 microduplication, a rare condition associated with psychomotor delay, behavioural disturbances and poor social interaction.

Methods

A.B., 57 years old, male, displayed obsessive and repetitive behaviours, irritability, scarce hygiene and memory loss at disease onset. He had strong familiarity for adult-onset behavioural alterations (his father and sister) and neuropsychiatric conditions (his son). Blood and cerebrospinal fluid (CSF) samples revealed 17q21.31 microduplication, shared also by his son and sister, and raised CSF tau, respectively. He was hospitalized 1 year after disease onset and underwent an MRI scan and a neuropsychological assessment, the latter being repeated 7 months later. To quantitatively investigate patient’s grey matter (GM) volume, 16 age- and education-matched male controls were selected and voxel-based morphometry analysis was performed.

Results

During hospitalization, his behavioural profile was characterized by anosognosia, impulsivity, apathy and aggressiveness. Cognitive testing revealed main attentive-executive disturbances and difficulties in understanding non-literal language. Compared to controls, A.B. had greater GM atrophy mainly in the right hemisphere, involving amygdala, hippocampus, inferior/superior temporal gyri and temporal pole. He received a diagnosis of early onset dementia. After 7 months, he developed empathy loss, perseverative behaviour, changes in eating habits and worsening in executive-attentive abilities.

Conclusions

In A.B., 17q21.31 microduplication caused a neurodegenerative condition with prevalent right temporal damage, raised CSF tau level, behavioural disturbances, memory impairment, attentive-executive and abstract language dysfunctions and fast disease progression, thus reflecting the complex interaction between such genetic substrate and clinical phenotypes.

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Availability of data and materials

All data needed to evaluate the conclusions in the paper are present in the paper and/or in the Supplementary Material. Additional data related to this paper may be requested from the corresponding author, upon reasonable request by qualified academic investigators.

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Funding

This study has been supported by the European Research Council (StG2016_714388_NeuroTRACK) and the Foundation Research on Alzheimer Disease.

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Authors and Affiliations

  1. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy

    Michela Leocadi, Elisa Canu, Camilla Cividini, Giordano Cecchetti, Federica Agosta & Massimo Filippi

  2. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Tommaso Russo, Giordano Cecchetti, Claudia Celico, Rosalinda Cardamone, Giuseppe Magnani, Federica Agosta & Massimo Filippi

  3. Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Giordano Cecchetti & Massimo Filippi

  4. Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  5. Vita-Salute San Raffaele University, Milan, Italy

    Michela Leocadi, Giordano Cecchetti, Federica Agosta & Massimo Filippi

  6. Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy

    Valeria Barcella

Authors
  1. Michela Leocadi
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  2. Elisa Canu
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  3. Camilla Cividini
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  4. Tommaso Russo
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  6. Claudia Celico
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  7. Rosalinda Cardamone
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  9. Giuseppe Magnani
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  10. Federica Agosta
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  11. Massimo Filippi
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Corresponding author

Correspondence to Massimo Filippi.

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Conflicts of interest

M. Leocadi, C. Cividini, G. Cecchetti, T. Russo, G. Magnani, C. Celico, R. Cardamone and V. Barcella report no actual or potential conflicts of interest. Dr. E. Canu has received research supports from the Italian Ministry of Health. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec, Roche and Zambon; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Ethical approval

The local ethical standards committee on human experimentation approved the study protocol and all participants provided written informed consent prior to be included in the present study.

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Leocadi, M., Canu, E., Cividini, C. et al. Brain structural abnormalities and cognitive changes in a patient with 17q21.31 microduplication and early onset dementia: a case report. J Neurol 270, 1127–1134 (2023). https://doi.org/10.1007/s00415-022-11423-1

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  • DOI: https://doi.org/10.1007/s00415-022-11423-1

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