Table 3.

Disorders Potentially Associated with Rapid Progression of Interest in the Differential Diagnosis of Genetic Prior Disease

EtiologyDisorder/CommentGene(s)
Hereditary
neurodegenerative
disorders 		CSF1R-related adult-onset leukoencephalopathy w/axonal spheroids & pigmented glia CSF1R
Dementia w/Lewy bodies (OMIM 127750)GBA1 (GBA)
SNCA
SNCB
Familial Alzheimer disease (See Alzheimer Disease Overview. 1) APP
PSEN1
PSEN2
Frontotemporal dementia (e.g., ALS/FTD, CHMP2B-FTD, GRN-FTD, IBMPFD)C9orf72 2
CHMP2B
FUS
GRN
HNRNPA1
HNRNPA2B1
TARDBP 3
VCP
Hereditary ataxia (e.g., SCA1, SCA2, SCA3, SCA6, SCA7, SCA8) 4 ATXN1
ATXN2
ATXN3
ATXN7
ATXN8
CACNA1A
Huntington disease HTT
Pick disease (OMIM 172700)MAPT 5
PSEN1
Progressive supranuclear palsy (OMIM 601104)MAPT 5
Autoimmune e.g., Hashimoto thyroiditis w/related encephalopathy, multiple sclerosis, antibody-mediated dementia/encephalopathy, CNS lupus, acute disseminated encephalomyelitis
Iatrogenic e.g., medication toxicity (e.g., lithium, methotrexate, chemotherapy), illicit drug use
Infectious e.g., viral encephalitis (incl herpes simplex virus), HIV dementia, progressive multifocal leukoencephalopathy
Metastases/
Neoplasm related 		e.g., paraneoplastic diseases-limbic encephalopathy, metastases to CNS, primary CNS lymphoma
Systemic/Seizures/
Structural 		e.g., sarcoidosis, epilepsy, nonconvulsive status epilepticus
Toxic-metabolic e.g., heavy metals (incl bismuth), electrolyte disturbances (sodium, calcium, magnesium, phosphorus), endocrine abnormalities (thyroid, parathyroid, adrenal), extrapontine myelinolysis
Vascular/Ischemia e.g., multi-infarct, thalamic or callosum infarcts, cerebral amyloid angiopathy

Adapted from Geschwind [2016], Table 7-4: Partial Differential Diagnosis for Rapidly Progressive Dementias by Etiologic Category

ALS = amyotrophic lateral sclerosis; CNS = central nervous system; FTD = frontotemporal dementia; HIV = human immunodeficiency virus; IBMPFD = inclusion body myopathy associated with Paget disease of bone and/or frontotemporal dementia

1.

Listed genes are associated with early-onset familial Alzheimer disease (EOFAD): Alzheimer disease that occurs in multiple members of a family with a mean onset usually before age 65 years. EOFAD represents fewer than 2% of Alzheimer disease cases. Late-onset familial Alzheimer disease (age >60-65 years), representing 15%-25% of Alzheimer disease cases, is thought to be a complex disorder possibly involving multiple susceptibility genes (see Alzheimer Disease Overview).

2.
3.
4.

The hereditary ataxias are a large group of autosomal dominant, autosomal recessive, and X-linked disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements; see Hereditary Ataxia Overview for molecular genetic and clinical information.

5.

From: Genetic Prion Disease

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