Details of Disease

General Information of Disease (ID: DIS7GBKQ)

• Disease Name: Essential tremor
• Synonyms: tremor, hereditary essential; essential hereditary tremor; shaky hand syndrome; benign essential tremor
• Definition: A relatively common disorder characterized by a fairly specific pattern of tremors which are most prominent in the upper extremities and neck, inducing titubations of the head. The tremor is usually mild, but when severe may be disabling. An autosomal dominant pattern of inheritance may occur in some families (i.e., familial tremor). (Mov Disord 1988;13(1):5-10)
• Disease Hierarchy:
  DISOJJ2D: Movement disorder
  DISD715V: Hereditary neurological disease
  DIS7GBKQ: Essential tremor
• Disease Identifiers:
  MONDO ID: MONDO_0003233
  MESH ID: D020329
  UMLS CUI: C0270736
  MedGen ID: 78725
  Orphanet ID: 862
  SNOMED CT ID: 609558009

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TUB	OTLY5BAC	Limited	Autosomal dominant	[1]
CCDC62	OTTIAOBP	Disputed	Biomarker	[18]
GABBR1	OTU5A52J	Disputed	Genetic Variation	[3]
GABRA4	OT5I7OI2	Disputed	Genetic Variation	[2]
HIP1R	OTIPKEJC	Disputed	Genetic Variation	[18]
PANK2	OTFBW889	Disputed	Genetic Variation	[19]
ANO3	OTM34U6Q	Strong	Genetic Variation	[20]
CHCHD2	OTL5PA3Y	Strong	Genetic Variation	[21]
CTNNA3	OT9Z0P1E	Strong	Genetic Variation	[22]
DNAJC13	OTYAVVJ6	Strong	Genetic Variation	[23]
HTRA2	OTC7616F	Strong	Genetic Variation	[20]
LINGO2	OT3N88Q1	Strong	Biomarker	[11]
LRRTM3	OTCS7EM6	Strong	Genetic Variation	[24]
LY6E	OTMG16BZ	Strong	Biomarker	[25]
MCF2L	OTEURA8N	Strong	Biomarker	[10]
PPP2R2B	OTSFVC82	Strong	Genetic Variation	[26]
SPCS3	OTAPFSUQ	Strong	Genetic Variation	[24]
TENM4	OT91K3FC	Strong	Biomarker	[27]
GK5	OT65U8L1	Definitive	Biomarker	[28]
KCNS2	OTVBVEIE	Definitive	Genetic Variation	[29]
PICALM	OTQVRPMQ	Definitive	Biomarker	[30]
RPGRIP1L	OT6Z069I	Definitive	Genetic Variation	[31]
SNAP91	OTE3EXWZ	Definitive	Biomarker	[30]

This Disease Is Related to 17 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GABRE	TTBY4OD	Disputed	Genetic Variation	[2]
GABRR1	TT6XFEU	Disputed	Genetic Variation	[3]
GABRR2	TTQMXLS	Disputed	Genetic Variation	[3]
GABRR3	TT4N6D8	Disputed	Genetic Variation	[3]
HCN1	TTNB6UQ	Disputed	Biomarker	[4]
SCN4A	TT84DRB	Disputed	Biomarker	[5]
ATXN3	TT6A17J	Strong	Biomarker	[6]
CHM	TTOA18V	Strong	Genetic Variation	[7]
CIT	TT3BKTU	Strong	Genetic Variation	[8]
GABRA1	TT1MPAY	Strong	Biomarker	[3]
HMOX2	TTWZRL4	Strong	Genetic Variation	[9]
LRP2	TTPH1AJ	Strong	Biomarker	[10]
RTN4R	TTVRZUO	Strong	Biomarker	[11]
STK32B	TT4D2GZ	Strong	Genetic Variation	[12]
CACNA1G	TT729IR	Definitive	Genetic Variation	[13]
SCN11A	TTN9VTF	Definitive	Genetic Variation	[14]
SLC38A7	TTEARWC	Definitive	Altered Expression	[15]

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP2C18	DEZMWRE	Disputed	Genetic Variation	[16]
CYP2C8	DES5XRU	Disputed	Biomarker	[16]
NDUFS7	DEIW03B	Definitive	Biomarker	[17]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Gamma-aminobutyric acid GABRA4, GABRE, and GABRQ receptor polymorphisms and risk for essential tremor.Pharmacogenet Genomics. 2011 Jul;21(7):436-9. doi: 10.1097/FPC.0b013e328345bec0.
• [3] Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for essential tremor.J Neurol. 2011 Feb;258(2):203-11. doi: 10.1007/s00415-010-5708-z. Epub 2010 Sep 5.
• [4] Hcn1 is a tremorgenic genetic component in a rat model of essential tremor.PLoS One. 2015 May 13;10(5):e0123529. doi: 10.1371/journal.pone.0123529. eCollection 2015.
• [5] SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.Hum Mol Genet. 2015 Dec 15;24(24):7111-20. doi: 10.1093/hmg/ddv410. Epub 2015 Oct 1.
• [6] Contextualizing the pathology in the essential tremor cerebellar cortex: a patholog-omics approach.Acta Neuropathol. 2019 Nov;138(5):859-876. doi: 10.1007/s00401-019-02043-7. Epub 2019 Jul 17.
• [7] Essential tremor is not associated with alpha-synuclein gene haplotypes.Mov Disord. 2003 Jul;18(7):823-6. doi: 10.1002/mds.10421.
• [8] Head-to-head comparison of (18) F-FP-CIT and (123) I-FP-CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study.Synapse. 2018 Jul;72(7):e22032. doi: 10.1002/syn.22032. Epub 2018 Mar 9.
• [9] Delta-amino-levulinic acid dehydratase gene and essential tremor.Eur J Clin Invest. 2017 May;47(5):348-356. doi: 10.1111/eci.12742. Epub 2017 Apr 7.
• [10] Decoding voluntary movements and postural tremor based on thalamic LFPs as a basis for closed-loop stimulation for essential tremor.Brain Stimul. 2019 Jul-Aug;12(4):858-867. doi: 10.1016/j.brs.2019.02.011. Epub 2019 Feb 21.
• [11] Increased LINGO1 in the cerebellum of essential tremor patients.Mov Disord. 2014 Nov;29(13):1637-47. doi: 10.1002/mds.25819. Epub 2014 Feb 14.
• [12] Assessment of Three New Loci from Genome-wide Association Study in Essential Tremor in Chinese population.Sci Rep. 2017 Aug 11;7(1):7981. doi: 10.1038/s41598-017-08863-5.
• [13] Whole genome sequencing and rare variant analysis in essential tremor families.PLoS One. 2019 Aug 12;14(8):e0220512. doi: 10.1371/journal.pone.0220512. eCollection 2019.
• [14] Gain-of-function mutation p.Arg225Cys in SCN11A causes familial episodic pain and contributes to essential tremor.J Hum Genet. 2017 Jun;62(6):641-646. doi: 10.1038/jhg.2017.21. Epub 2017 Mar 16.
• [15] Excitatory Amino acid transporter expression in the essential tremor dentate nucleus and cerebellar cortex: A postmortem study.Parkinsonism Relat Disord. 2016 Nov;32:87-93. doi: 10.1016/j.parkreldis.2016.09.003. Epub 2016 Sep 6.
• [16] Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor.Neuromolecular Med. 2007;9(2):195-204. doi: 10.1007/BF02685892.
• [17] Hyperechogenicity of substantia nigra for differential diagnosis of Parkinson's disease: A meta-analysis.Parkinsonism Relat Disord. 2017 Sep;42:1-11. doi: 10.1016/j.parkreldis.2017.06.006. Epub 2017 Jun 15.
• [18] Genetics of Parkinson's disease and essential tremor.Curr Opin Neurol. 2011 Aug;24(4):318-23. doi: 10.1097/WCO.0b013e3283484b87.
• [19] Pantothenate kinase-associated neurodegeneration initially presenting as postural tremor alone in a Japanese family with homozygous N245S substitutions in the pantothenate kinase gene.J Neurol Sci. 2004 Oct 15;225(1-2):129-33. doi: 10.1016/j.jns.2004.07.012.
• [20] A step toward essential tremor gene discovery: identification of extreme phenotype and screening of HTRA2 and ANO3.BMC Neurol. 2016 Nov 23;16(1):238. doi: 10.1186/s12883-016-0748-3.
• [21] Mutation analysis of CHCHD2 gene in Chinese Han familial essential tremor patients and familial Parkinson's disease patients.Neurobiol Aging. 2017 Jan;49:218.e9-218.e11. doi: 10.1016/j.neurobiolaging.2016.10.001. Epub 2016 Oct 11.
• [22] Analysis of Single Nucleotide Polymorphisms of STK32B, PPARGC1A and CTNNA3 Gene With Sporadic Parkinson's Disease Susceptibility in Chinese Han Population.Front Neurol. 2018 May 30;9:387. doi: 10.3389/fneur.2018.00387. eCollection 2018.
• [23] VPS35 and DNAJC13 disease-causing variants in essential tremor.Eur J Hum Genet. 2015 Jun;23(6):887-8. doi: 10.1038/ejhg.2014.164. Epub 2014 Aug 13.
• [24] Genome-wide association study in essential tremor identifies three new loci.Brain. 2016 Dec;139(Pt 12):3163-3169. doi: 10.1093/brain/aww242. Epub 2016 Oct 20.
• [25] A Quantitative Study of Empty Baskets in Essential Tremor and Other Motor Neurodegenerative Diseases.J Neuropathol Exp Neurol. 2019 Feb 1;78(2):113-122. doi: 10.1093/jnen/nly114.
• [26] PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):124-9. doi: 10.1002/ajmg.b.30785.
• [27] Teneurin transmembrane protein 4 is not a cause for essential tremor in a Canadian population.Mov Disord. 2017 Feb;32(2):292-295. doi: 10.1002/mds.26753. Epub 2017 Feb 3.
• [28] Functional lesional neurosurgery for tremor: a systematic review and meta-analysis.J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):717-726. doi: 10.1136/jnnp-2017-316302. Epub 2018 Jan 11.
• [29] A Drosophila Model of Essential Tremor.Sci Rep. 2018 May 16;8(1):7664. doi: 10.1038/s41598-018-25949-w.
• [30] A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of CX-8998, a Selective Modulator of the T-Type Calcium Channel in Inadequately Treated Moderate to Severe Essential Tremor: T-CALM Study Design and Methodology for Efficacy Endpoint and Digital Biomarker Selection.Front Neurol. 2019 Jun 11;10:597. doi: 10.3389/fneur.2019.00597. eCollection 2019.
• [31] Role of altered cerebello-thalamo-cortical network in the neurobiology of essential tremor.Neuroradiology. 2017 Feb;59(2):157-168. doi: 10.1007/s00234-016-1771-1. Epub 2017 Jan 6.