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Autosomal Dominant Gene Negative Frontotemporal Dementia-Think of SCA17

  • Diana Angelika OlszewskaEmail author
  • E. M. Fallon
  • G. M. Pastores
  • K. Murphy
  • A. Blanco
  • T. Lynch
  • S. M. Murphy
Short Report

Abstract

SCA 17 is a rare, autosomal dominant disorder caused by TBP gene CAG/CAA repeat expansion. Ataxia and dementia are common. The presence of frontal dysfunction at outset of the disease may mimic frontotemporal dementia (FTD). Parkinsonism, chorea, dystonia, and pyramidal signs may occur. We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17 and present detailed neuropsychological assessment for the first time. A 44-year-old doctor presented with 18-month history of behavioral problems. She slowed down, became apathetic, and unable to multitask. She became more irritable and short tempered, and her work performance deteriorated. Brain MRI showed cerebellar atrophy and cerebellar hypometabolism was noted on FDG-PET. A sister developed personality changes at age 45 with apathy, and had problems with memory and social skills; another sister at age 39 became dysarthric and unsteady. A brother at age 52 demonstrated emotional lability, and became dysarthric, unsteady, and slowed down. Their mother aged 73 had an abnormal antalgic gait due to arthritis; their father was jocular and disinhibited. MAPT testing detected an exon 9 c.726C>T variant in the proband. Subsequent testing in nine siblings and both parents failed to show co-segregation with disease. SCA17 testing revealed a TBP gene 43 repeat expansion that co-segregated in all affected siblings and in the mother whose gait problems were initially attributed to arthritis. In over 80% of cases of FTD with clear autosomal dominant inheritance, causative gene defects involve MAPT, GRN, or C9orf72 mutations. A minority involves VCP, FUS, and CHMP2B. As evident from our case, SCA17 testing should also be considered, especially if cerebellar atrophy if found on imaging. Segregation analysis is crucial. MAPT variant (c.726C>T exon 9) detected in the family was deemed a polymorphism.

Keywords

SCA 17 Frontal symptoms FTD Ataxia 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Diana Angelika Olszewska
    • 1
    Email author
  • E. M. Fallon
    • 1
  • G. M. Pastores
    • 2
  • K. Murphy
    • 3
  • A. Blanco
    • 4
  • T. Lynch
    • 1
  • S. M. Murphy
    • 5
    • 6
  1. 1.Department of Neurology, Dublin Neurological InstituteMater Misericordiae University HospitalDublin 7Ireland
  2. 2.National Centre for Inherited Metabolic DisordersMater Misericordiae University HospitalDublinIreland
  3. 3.Department of NeurologySligo University HospitalSligoIreland
  4. 4.Department of NeuropsychologyMater Misericordiae University HospitalDublinIreland
  5. 5.Department of NeurologyThe Adelaide and Meath HospitalsDublinIreland
  6. 6.Academic Unit of NeurologyTrinity College DublinDublinIreland

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