Psychosis and Hallucinations in Frontotemporal Dementia with the C9ORF72 Mutation: A Detailed Clinical Cohort

Objective:To specify the presenting symptoms and clinical course of patients with frontotemporal dementia (FTD) and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. Background:The 2011 discovery of the C9ORF72 repeat expansion causing familial FTD and amyotrophic lateral sclerosis has permitted retrospective evaluation of potential defining clinical characteristics that may distinguish carriers of the C9ORF72 mutation from other patients with FTD. Prior reports identified a subset of patients with FTD who had an unusually high prevalence of psychosis, although their specific symptoms had not yet been fully described. Methods:From a cohort of 62 patients with FTD, we conducted a retrospective chart review of 7 patients who had C9ORF72 mutations on genetic testing, and 1 untested sibling of a C9ORF72 carrier. Results:Detailed histories revealed a higher prevalence of psychosis, including visual and auditory hallucinations and delusions, in the 8 C9ORF72 carriers than in our patients with sporadic FTD. Conclusions:This cohort confirms and adds clinical details to the reports of a high prevalence of psychotic phenomena in patients who have C9ORF72 mutations as well as FTD or amyotrophic lateral sclerosis.

[1]  P. Johannsen,et al.  Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease , 2013, Clinical genetics.

[2]  D. Geschwind,et al.  Frontotemporal dementia due to C9ORF72 mutations , 2012, Neurology.

[3]  N. Williams,et al.  Recent Advances in the Genetics of the ALS-FTLD Complex , 2012, Current Neurology and Neuroscience Reports.

[4]  Janel O. Johnson,et al.  Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study , 2012, The Lancet Neurology.

[5]  V. Meininger,et al.  Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes , 2012, Journal of Medical Genetics.

[6]  D. Neary,et al.  Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. , 2012, Brain : a journal of neurology.

[7]  Y. Pijnenburg,et al.  The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. , 2012, Brain : a journal of neurology.

[8]  H. Feldman,et al.  Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. , 2012, Brain : a journal of neurology.

[9]  Nick C Fox,et al.  Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features , 2012, Alzheimer's & Dementia.

[10]  S. Pereson,et al.  A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study , 2012, The Lancet Neurology.

[11]  H. Feldman,et al.  Clinical and pathological features of familial frontotemporal dementia caused by C 9 ORF 72 mutation on chromosome 9 p , 2012 .

[12]  N. Bresolin,et al.  Early onset behavioral variant frontotemporal dementia due to the C9ORF72 hexanucleotide repeat expansion: psychiatric clinical presentations. , 2012, Journal of Alzheimer's disease : JAD.

[13]  Bruce L. Miller,et al.  Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS , 2011, Neuron.

[14]  David Heckerman,et al.  A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD , 2011, Neuron.

[15]  Nick C Fox,et al.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. , 2011, Brain : a journal of neurology.

[16]  J. Trojanowski,et al.  A harmonized classification system for FTLD-TDP pathology , 2011, Acta Neuropathologica.

[17]  D. Hernandez,et al.  Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p , 2011, Journal of Neurology.

[18]  P. S. St George-Hyslop,et al.  Intra-familial clinical heterogeneity due to FTLD-U with TDP-43 proteinopathy caused by a novel deletion in progranulin gene (PGRN). , 2011, Journal of Alzheimer's disease : JAD.

[19]  J. Hodges,et al.  Neurobehavioral features in frontotemporal dementia with amyotrophic lateral sclerosis. , 2010, Archives of neurology.

[20]  B. Boeve,et al.  Frontotemporal Dementia Mimicking Dementia With Lewy Bodies , 2008, Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology.

[21]  A. Kertesz,et al.  Delusions and Hallucinations in Frontotemporal Dementia: A Clinicopathologic Case Report , 2008, Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology.

[22]  M. Mendez,et al.  Accuracy of the clinical evaluation for frontotemporal dementia. , 2007, Archives of neurology.

[23]  Catherine Lomen-Hoerth,et al.  The overlap of amyotrophic lateral sclerosis and frontotemporal dementia , 2002, Neurology.

[24]  R. Faber,et al.  Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. , 1999, Neurology.

[25]  R. Nitrini,et al.  Psychotic symptoms in dementia associated with motor neuron disease: a pathophysiological hypothesis. , 1998, The Journal of neuropsychiatry and clinical neurosciences.

[26]  A. Kertesz,et al.  Frontal Behavioral Inventory: Diagnostic Criteria for Frontal Lobe Dementi , 1997, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[27]  M. Mega,et al.  The Neuropsychiatric Inventory , 1994, Neurology.

[28]  J. Corrigan,et al.  Relationships between parts A and B of the Trail Making Test. , 1987, Journal of clinical psychology.

[29]  A. Kertesz.  The Western Aphasia Battery , 1982 .

[30]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[31]  J. Raven,et al.  Manual for Raven's progressive matrices and vocabulary scales , 1962 .