| Demographic |
Males and females appear approximately equally affected Age of onset is between 33 and 72 years, with most presenting in the 40–70 year age range Survival is variable but typically in the 3–10 year range Survival is shorter when the ALS phenotype is present
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| Inheritance |
Inheritance is autosomal dominant Some examples of incomplete penetrance do exist Apparently sporadic cases do exist Some kindreds appear to exhibit an anticipation-like phenomenon
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| Clinical |
The characteristic phenotypes include behavioural variant FTD, ALS or FTD/ALS Many with the behavioural variant FTD predominant phenotype have evidence of upper and/or lower motor neuron involvement Some with the ALS predominant phenotype have features of behavioural variant FTD The primary progressive aphasia and corticobasal syndrome phenotypes appear to be uncommonly associated with this mutation Psychosis and appetite/eating changes are common Parkinsonism is common and typically of the akinetic-rigid type without tremor
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| Neuropsychological |
Most cases have impairment on measures of complex attention/executive functioning and verbal fluency Performance in other domains is more variable, with most having more minimal or no impairment on measures of episodic memory, confrontation naming and visuospatial functioning
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| Neuroimaging |
On MRI, most cases have symmetric bilateral frontal ± temporal cortical atrophy; remarkably minimal atrophy can be apparent early in the course On SPECT or PET, most cases have symmetric bilateral frontal ± temporal cortical abnormalities, with the anteromedial cingulate region being most consistently affected
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| Neuropathology |
All cases have TDP-43 positive pathology, with some having features most consistent with harmonized type A FTLD-TDP pathology and others having features most consistent with type B pathology. Ubiquitin-positive neuronal inclusions are very common in the cerebellar granule cells. Motor neuron degeneration and substantia nigra degeneration are common. Hippocampal sclerosis is uncommon or less severe in cases with motor neuron disease
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