Heritability & genetics in essential tremor

genetics movement disorders Essential tremor

prof. dr. M.A.J. de Koning-Tijssen
Dr. A.M.M. van der Stouwe

Type of project:
Stage Wetenschap / Research project

Nature of the research:
The student is getting on board with a team of movement disorders neurologists/researchers. The student will focus on the investigation of families of essential tremor patients. More information:

Fields of study:
neurology genetics

Background / introduction
Tremor is one of the most common neurological disorders. It is a disorder studied within Movement Disorders Groningen, as much remains to be unraveled concerning pathophysiology, diagnostic strategies and treatment.

Essential tremor is characterized by a bilateral, involuntary, rhythmic shaking (tremor) of the hands, occurring during movement or when the patient tries to maintain a specific position. The main phenotype includes tremor of the hands (in 97% of patients), voice (62%), head (48%), and to a lesser extent the jaw, tongue, legs and feet. The tremor can be very prominent, complicating simple activities of daily life such as drinking a cup of coffee and shaving, as well as compromising professional achievements in technical jobs such as an electrician. Imagine a surgeon developing essential tremor: it would mean the end of his career. Another aspect is that some patients feel embarrassed in social situations such as dining in a restaurant, even to the extent that they would rather stay home.

Interestingly, half of the patients report a family history. As a consequence, it sometimes happens that one family member visits a neurologist and gets diagnosed, and in a little while the entire family is treated. In most affected families, essential tremor appears to inherit in an autosomal dominant pattern. However, a causal gene for essential tremor has not been found.

The proposed reason for the poor outcome in genetic investigations so far is that different subtypes of essential tremor exist with distinct etiologies. In other words, different types of tremor have been pooled in previous studies, and as a result no common mutations were found. To make progress in genetics, it is going to be essential to define clinical subtypes and study these in separate genetic analyses.

At the UMCG, we have conducted an imaging study with essential tremor patients, paying a lot of attention to diagnosing our patients correctly. Consequently, we have acquired a number of well-studied essential tremor patients, half of whom report a family history with tremor. Moreover, we have an extensive database including essential tremor patients. Together, these provide a great cohort to study heritability and genetics.

Moreover, we have recently started a large, new project, aimed at the development of a computer aided diagnosis tool, that will make use of EMG, accelerometry and 3D video to differentiate different types of movement disorers. We would like to apply this technique in families with essential tremor as well.
Research question / problem definition
1. What are the inheritance patterns in the essential tremor patients of the Groningen cohort?
2. Can we define a clinical subtype? In other words: do certain features cluster within families?
3. When we have defined a clinical subtype, we will proceed to the third question: what are the genetics involved in the families of this subtype?
The student will get in touch with patients that participated in, or applied for participation in our previous essential tremor study, to come up with family trees (pedigrees) of the patients. Moreover, we will select patients from our database to be approached. Patients are investigated clinically by the student, and by means of clinical neurophysiology (EMG, accelerometers). If possible, we will use our computer aided diagnosis set up to investigate patients and define a clinical subtype using machine learning.
When we have defined a clinical subtype, we will proceed to genetic testing, with blood samples that will have already been stored at the Department of Clinical Genetics.
- Zeuner KE, Deuschl G. An update on tremors. Current opinion in neurology. 2012 Aug;25(4):475-82.
- Hopfner F, et al. Knowledge gaps and research recommendations for essential tremor. Parkinsonism and Related Disorders. 2016 Dec;33:27-35.
- Van der Stouwe AM, et al. How typical are ‘typical’ tremor characteristics? Sensitivity and specificity of five tremor phenomena. Clinical Neurophysiology, 2016 Sep;30:23-8
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Laatst gewijzigd: 23 februari 2012