Table 1.
Neuropsychiatric features reported in C9orf72 expansion carriers
| UCSF MACa | Snowden and colleagues [4] | Mahoney and colleagues [6] | Hsiung and colleagues [17] | Boeve and colleagues [7] | Chio and colleagues [20] | Simón-Sanchez and colleagues [23] | Byrne and colleagues [18] | ||
|---|---|---|---|---|---|---|---|---|---|
| Phenotype of carriersb | 14 bvFTD | 19 bvFTD, 1 SD/FTD, 3 PNFA | 12 bvFTD, 1 PNFA | 15 bvFTD | 16 bvFTD | - | 28 bvFTD 7 PPA |
- | |
| 11 FTD-MND | 9 FTD-MND | 3 FTD-MND | 7 FTD-MND | 3 FTD-MND | 30 FTD-MND | 6 FTD-MND, 1 PPA-MND | 10 FTD-MND | ||
| 8 ALS | 1 ALS | 36 ALS | - | 11 ALS | |||||
| Controls (noncarriers)c | 45 bvFTD | 19 FTD-MND | 366 noncarriers | NA | NA | NA | NAd | NA | 166 ALS (± FTD) |
| Number screened | 648 | 398 | 234 | 22 | 604 | 182 | 363 | 435 | |
| Assessment method | RCR and NPI | Structured pro-forma | RCR | RCR | RCR | FSBS and RCRe | RCR | FSBS | |
| Disinhibition | 85% | 63% | 66% | 63 → 76% | 40 → 70% | NA | 13%e | 26% | NA |
| Apathy/inertia | 64% | 36% | 88% | 49 → 63% | 30 → 47% | NA | 100%e | 43% | NA |
| Loss of sympathy/empathy | 57% | 45% | 77% | ~12 → ~18% | NA | NA | NA | NA | NA |
| Perseverative/compulsive behavior | 50% repet., 50% comp. | 18% repet., 54% comp. | 75% repet./stereotypic | ~25 → 50% obsessive | 27 → 50% rigidity/persev. | NA | 1.5% acute OCD | 12% OCD | NA |
| Hyperorality | 50% | 27% | 43% | NA | NA | 100% | NA | NA | NA |
| Anxiety | NA | NA | NA | ~39 → 52% | NA | NA | NA | NA | NA |
| Delusions | 42% | 36% | 50% | 0 → ~12% | 3% | 45% | 4%f | 0 | NA |
| Hallucinations | 7% | 9% | 19% | ~6 → ~12% | 0 | 50% | 4%f | 5% | NA |
| Lack of insight | NA | NA | 78% | NA | NA | NA | NA | NA | NA |
Reported at first assessment (UCSF MAC and [4,23]), during course of disease [7,20] or at first and final evaluation [6,17]. Byrne and colleagues did not report frequencies [18]. Number before arrow, frequency at first assessment; number after arrow, frequency at last assessment. ALS, amyotrophic lateral sclerosis; bvFTD, behavioral variant frontotemporal dementia; comp., compulsive; C9orf72, chromosome 9 open reading frame 72; FSBS, Frontal Systems Behavior Scale; FTD, frontotemporal dementia; MND, motor neuron disease; NA, not available; NPI, Neuropsychiatric Inventory; OCD, obsessive-compulsive disorder; persev., perseverative; PNFA, progressive nonfluent aphasia; PPA, primary progressive aphasia; RCR, retrospective chart review; repet., repetitive; SD, semantic dementia; UCSF MAC, University of California, San Francisco Memory and Aging Center. aBased on data collected for Sha and colleagues [5], but not included in the final manuscript. bNumber of patients included in symptom frequency analysis. cControls used for comparison of clinical features. dFifty-seven carriers with other ALS-causing mutations were used as controls for clinical features of MND, but not for behavioral changes. eTwenty-three of the 66 carriers were assessed with the FSBS (Family Rating Form) - percentages reflect only those evaluated with the scale. fFrequency of psychosis (hallucinations and/or delusions were reported in three out of 66 patients).