Imaging Genetics of Laryngeal Dystonia
Kristina Simonyan
Summary
The contribution of genetic risk factors to the development of focal dystonias is evident. However, understanding of how variations in the causative gene expression lead to variations in brain abnormalities in different phenotypes of dystonia (e.g., familial, sporadic) remains limited. The research program of the investigators is set to determine the relationship between brain changes and genetic risk factors in laryngeal dystonia (or spasmodic dysphonia). The researchers use a novel approach of combined imaging genetics, next-generation DNA sequencing, and clinical-behavioral testing. The use of a cross-disciplinary approach as a tool for the discovery of the mediating neural mechanisms that bridge the gap from DNA sequence to the pathophysiology of dystonia holds a promise for the understanding of the mechanistic aspects of brain function affected by risk gene variants, which can be used reliably for the discovery of associated genes and neural integrity markers for this disorder. The expected outcome of this study may lead to better clinical management of this disorder, including its improved detection, accurate diagnosis, and assessment of the risk of developing dystonia in family members.
Description
Laryngeal dystonia (LD), or spasmodic dysphonia, is an isolated focal dystonia characterized by selective impairment of speech production due to involuntary spasms in the laryngeal muscles. Despite the well-characterized clinical features of LD, its clinical management remains challenging due, in part, to the absence of objective measures (biomarkers) for early detection and differential diagnosis. This results in diagnostic inaccuracies, which have a negative impact on the patient's quality of life and healthcare costs. Importantly, delayed diagnosis leads to deferred treatment. The objective…
Eligibility
- Age range
- Not specified
- Sex
- All
- Healthy volunteers
- No
Inclusion criteria: 1. Males and females of diverse racial and ethnic background, with age across the lifespan; 2. Laryngeal Dystonia patients * phenotype: adductor or abductor * genotype: familial or sporadic 3. Voice Tremor patients * essential or * dystonic 4. Muscle tension dysphonia patients 5. Unaffected relatives of laryngeal dystonia patients with * familial laryngeal dystonia * early-onset laryngeal dystonia (onset at ≤ 35 y.o.) * typical onset laryngeal dystonia (onset at ≥ 40 y.o.) 6. Native English speakers. 7. Right-handedness. 8. Normal cognitive status.…
Interventions
- OtherMRI
Functional and structural MRI of the brain will be conducted to identify disorder specific neural markers
- ProcedureBlood draw
Blood samples will be collected, the DNA will be extracted and banked for genetic studies.
Location
- Massachusetts Eye and Ear InfirmaryBoston, Massachusetts