Characteristics of Idiopathic Familial Voice Disorders

The purpose the study is to determine the genetic causes of specific voice disorders that run in families. Researchers are particularly interested in two conditions;

1. Spasmodic dysphonia
2. Vocal fold paralysis

Familial vocal fold paralysis can be a life-threatening disorder that can cause difficulty with vocal fold movement for breathing and voice and sometimes for swallowing. Studies are ongoing at the NIH to better understand the pathophysiology and to relate it to the genetic pattern of inheritance. Families are being recruited to participate in these studies and are being provided with further information on the disorder and genetic counseling if desired. Physician referral is requested for affected members of families with vocal fold paralysis of an unknown cause occurring over at least 2 generations. All travel, lodging, examination and counseling costs are covered for both affected and unaffected members of a family. Examinations include: voice, laryngeal, neurological, electrodiagnostic testing, genetic counseling, and radiological studies....

OBJECTIVE:

Our purpose is to examine for evidence of genetic risk factors associated with idiopathic laryngeal motor control disorders. During the conception of the protocol, we were interested in investigating the pattern of inheritance of familial voice disorders, specifically spasmodic dysphonia and tremor. Interestingly, the initial search for families revealed several large families with idiopathic vocal fold paralysis with some family members experiencing symptoms of spasmodic dysphonia. During subsequent years, the research has focused on inherited forms of vocal fold paralysis in an attempt to determine the relationship between the laryngeal motor control disorder and other associated neuropathies, and to determine the existence of a specific genetic abnormality. These idiopathic laryngeal motor control disorders were one manifestation of peripheral neuropathies or may be an isolated disorder with only laryngeal involvement. Subsequently, we have shifted our emphasis back to the identification of genetic risk factors for spasmodic dysphonia.

Hypothesis 1) Familial risk factors for spasmodic dysphonia result in a particular phenotype and genotype.

Hypothesis 2) Environmental risk factors may differentiate between affected and unaffected members of families with spasmodic dysphonia.

Hypothesis 3) Whole genome screening will identify SNPs associated with the occurrence of spasmodic dysphonia.

STUDY POPULATION:

Families with multiple members affected with spasmodic dysphonia, vocal fold paralysis, and tremor will be ascertained.

DESIGN:

A pedigree will be developed via a questionnaire and voice history. Affected and unaffected family members will be examined to determine the presence and extent of their laryngeal motor control disorder. Affected family members will also undergo neurological examination and nerve and muscle studies to determine the loci of their pathology. A genotype will be developed for affected and unaffected family members, through DNA testing of blood samples.

OUTCOME MEASURES:

This is a natural history study characterizing the phenotype and genotype of idiopathic laryngeal motor control disorders.