Details of Disease

General Information of Disease (ID: DISPZM6A)

• Disease Name: Frontotemporal dementia with motor neuron disease
• Synonyms: FTDALS; frontotemporal dementia with ALS; FTD-ALS; frontotemporal dementia with amyotrophic lateral sclerosis; FTD-MND
• Definition: Frontotemporal dementia with motor neuron disease (FTD-MND) is a type of frontotemporal lobar degeneration characterized by the insidious onset (between the ages of 38-78 years) of dementia-associated psychiatric symptoms (e.g. personality changes, uninhibited behavior, irritability, aggressiveness), memory difficulties, global intellectual impairment, emotional disorders and transcortical motor aphasia that eventually leads to mutism, in addition to the manifestations of motor neuron disease such as neurogenic muscular wasting (similar to what is seen in amyotrophic lateral sclerosis). The disease is progressive, with death occurring 2-5 years after onset.
• Disease Hierarchy:
  DISFWL8F: Hereditary dementia
  DISPN7D2: Inherited neurodegenerative disorder
  DISOJJ2D: Movement disorder
  DISPZM6A: Frontotemporal dementia with motor neuron disease

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
VCP	OTWIX1JU	Supportive	Autosomal dominant	[1]
CHCHD10	OTCDHAM6	Supportive	Autosomal dominant	[5]
SQSTM1	OTGY5D5J	Supportive	Autosomal dominant	[2]
TARDBP	OTVOSFWW	Supportive	Autosomal dominant	[3]
TBK1	OT1P06NV	Supportive	Autosomal dominant	[4]

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SQSTM1	TTOT2RY	Supportive	Autosomal dominant	[2]
TARDBP	TT9RZ03	Supportive	Autosomal dominant	[3]
TBK1	TTH5TC2	Supportive	Autosomal dominant	[4]
VCP	TTYWTI0	Supportive	Autosomal dominant	[1]

References

• [1] Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010 Dec 9;68(5):857-64. doi: 10.1016/j.neuron.2010.11.036.
• [2] SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. JAMA Neurol. 2013 Nov;70(11):1403-10. doi: 10.1001/jamaneurol.2013.3849.
• [3] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [4] Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci. 2015 May;18(5):631-6. doi: 10.1038/nn.4000. Epub 2015 Mar 24.
• [5] A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. Brain. 2014 Aug;137(Pt 8):2329-45. doi: 10.1093/brain/awu138. Epub 2014 Jun 16.