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Table 1 Key features of c9FTD/ALS due to the GGGGCC hexanucleotide repeat expansion in C9ORF72 across published series with ample numbers of cases with the FTD ± ALS phenotype

From: Cognitive and behavioral features of c9FTD/ALS

Feature Mayo Clinic Mayo Clinic Brain Bank Manchester Vancouver Dutch London Flanders Belgian NIH/NINDS Irish Total
Reference in text [21] [20] [28] [25] [27] [26] [24] [29] [21]  
Cohort characteristics           
   Number of cases examined (with mutation) 53 (63) 13 (13) 32 (32) 30 (30) 42 (42) 19 (19) 41 (41) 4 (4) 10 (10) 254
   Number of kindreds identified 43 20 32 16 37 18 25 4 39 234
   Percentage of all FTD ± ALS caes with mutation due to C9ORF72/PGRN/MAPT 12/4/6 NA 8/0/0 55/24/NA 9/7/10 7/7/6 8/7/1 8% for C9ORF72 9% for C9ORF72 Most in 7%-12% range
   Percentage of familial FTD ± cases with mutation due to C9ORF72/PGRN/MAPT 20/6/11 NA ? 70/30/NA 18/14/22 13/14/14 26/22/4 NA NA Most in 13%-26% range
   Percentage of FTD cases not due to known genes 66 NA ? ? 46 45 56 NA NA 45%-66% range
Demographics           
   Males/Females 33/30 8/5 18/14 21/8 20/22 11/8 8/7 ? 10/11 129/105
   Age of onset in years, mean or median 52 65 58 54 57 55 55 58 56 52-65 range
   Age of onset in years, range 33-72 50-78 46-72 34-74 39-76 43-68 38-71 ? ? 33-78 range
   Survival in years, mean or median 5 5 ? 5 7 9 5 ? ? 5-9 range
   Survival in years, range 1-17 3-11 1-11 1-16 1-22 1-22 2-17 ? ? 1-22 range
Inheritance           
   Inheritance pattern AD AD AD AD AD AD AD AD AD AD
   Frequency of sporadic cases ++ ++ ++ ++ ++ ++ ++ ++ + ++
   Penetrance High High High High High High High High High High
   Anticipation suggested ++ ? ? ++ ? ? ? + ? Many reports
Clinical phenotype           
   bvFTD phenotype +++ ++ +++ +++ +++ +++ +++ ++ 0 Frequent
   ALS phenotype ++ NA NA ++ ++ NA ++ 0 +++ Often
   FTD/ALS phenotype ++ 0 ++ ++ ++ ++ ++ ++ ++ Often
   Primary parkinsonian phenotype 0 0 0 0 0 0 0 0 0 None reported
   Non-fluent/agrammatic subtype of PPA 0 0 + ++ ++ + 0 0 0 Rare
   Semantic subtype of PPA 0 0 + 0 + 0 0 0 0 Rare
   Corticobasal syndrome phenotype 0 0 NA 0 0 0 0 0 0 None reported
   Alzheimer's disease-like phenotype + ++ NA + 0 + 0 0 0 Rare
Cognitive features           
   Memory impairment ++ +++ ++ +++ +++ +++ ? ? 0 Often to frequent
   Executive functioning impairment +++ +++ +++ +++ +++ +++ Presumably Presumably ++ Frequent
   Language impairment (aphasia) ++ ++ +++ +++ ++ +++ ? ? 0 Frequent and usually late feature
   Visuospatial impairment + ? + + + + ? ? ? Rare
   Neuropsychological profile of executive/generation deficits with relative sparing of memory and visuospatial functions ++ Presumably in some ++ ++ ? ++ Presumably in many Presumably in many ++ Often but certainly not frequent
Behavioral features           
   Early behavioral disinhibition +++ Presumably +++ +++ ++ +++ Presumably Presumably Presumably Frequent
   Early apathy or inertia +++ Presumably +++ +++ ++ +++ Presumably Presumably Presumably Frequent
   Early loss of sympathy or empathy +++ Presumably +++ +++ ? ++ Presumably Presumably Presumably Frequent
   Hyperorality and dietary changes +++ Presumably +++ ? ? +++ Presumably Presumably Presumably Frequent
   Pseudobulbar affect + ? ? ? ? ? ? ? ? Insufficient data
   Psychosis (delusions or hallucinations) ++ ? ++ + + ++ ? ? ? Often
Other clinical features           
   Frontal release signs ++ ? ++ ? ? ? ? ? ? Insufficient data
   Parkinsonism ++ ++ ++ ++ ? ++ ? ? ? Often
   Upper or lower (or both) motor neuron dysfunction not fulfilling ALS criteria ++ ? + ++ ? +++ ? ? ? Often
   ALS ++ 0 ++ ++ ++ ++ ++ 0 +++ Often in FTD
   Limb apraxia 0 ? 0 + + 0 ? ? ? Rare
  1. The Manchester series only included cases with a frontotemporal dementia (FTD) spectrum dementia syndrome and not amyotrophic lateral sclerosis (ALS) or parkinsonism. In the Vancouver series, cases of FTD or ALS or both had progressive non-fluent aphasia plus frontal features and ALS. The percent breakdowns of chromosome 9 open reading frame 72 (C9ORF72) and progranulin (PGRN) are based on autopsied cases with TDP-43+ pathology, not all FTD cases. The Irish series involved mostly ALS cases, of which 10 had FTD or ALS or both. 0, feature reported as not present; +, feature reported as present infrequently (<10% of cases); ++, feature reported as often present (10% to 50% of cases); +++, feature reported as frequently present (>50% of cases); ?, feature not discussed sufficiently in the report to make any determinations. AD, Alzheimer's disease; bvFTD, behavioral variant frontotemporal dementia; c9FTD/ALS, frontotemporal dementia or amyotrophic lateral sclerosis (or both) linked to chromosome 9; GGGGCC, (the hexanucleotide expansion of) guanine-guanine-guanine-guanine-cytosine-cytosine; MAPT, microtubule-associated protein tau; NA, not applicable; NIH/NINDS, National Institutes of Health/National Institute of Neurological Disorders and Stroke; PPA, primary progressive aphasia.