Dysautonomia Foundation

Name of disease: familial dysautonomia (FD), also known as Riley-Day Syndrome
Carrier frequency in Ashkenazi Jews: 1 in 27
Carrier frequency in the general population: unknown
Age of onset: birth

Symptoms: FD causes dysfunction of the autonomic and sensory nervous systems. It is a progressive disease. Symptoms and severity vary in each patient. Symptoms include:

Absence of overflow tears / corneal drying
Poor suck at birth
Drooling
Swallowing & feeding problems
Hypotonia / poor muscle tone
Short stature
Delayed developmental milestones: motor, language, social
Inappropriate temperature controls
Wide swings in blood pressure
Gastro-esophageal reflux
Frequent lung infections or pneumonias

Episodic vomiting
Decreased or no reaction to pain and temperature
Excessive sweating
Blotchy reddening of skin with excitement and/or feeding
Smooth tongue / lack of taste buds
Spinal curvature
Poor weight gain and growth
Impaired renal function
Osteoporosis and osteopenia
Fainting and cardiac arrhythmias
Sleep apnea
Restrictive lung disease

Average lifespan: Currently, the mean age of the FD population is approximately 15 years. By statistical projection, babies born with FD in 2006 have a 50% chance of surviving to 40 years of age. The major causes of death are the result of pulmonary complications or sudden death due to autonomic instability.

What is the basis of disease: Inefficient gene splicing results in decreased production of a vital protein called IKAP. This protein is an essential component of a complex that aids in expression of multiple other target genes that are critical for growth and development of the sensory and autonomic nervous systems as well as their function.

Treatment or management: At present, only supportive treatments are available. Supportive therapies include topical lubrication of the eyes and medications to maintain and regulate cardiovascular, respiratory, and gastrointestinal function. Surgical interventions include fundoplication, gastrostomy, spinal fusion, and tear duct cautery. Various therapies are used to promote strength and speech development.

Carrier testing: Carrier testing is available for the two most common mutations. All patients have one or two copies of a single splicing mutation; over 99% of cases of FD in the Ashkenazi Jewish (AJ) population have two copies of this splicing mutation. A second mutation paired with the AJ splicing mutation accounts for all other cases in the AJ population. A third mutation from a non-Jewish parent, again paired with the AJ splicing mutation, is responsible for a single case of FD.

Other testing information: Carrier screening is based on DNA analysis. Screening is 99% accurate for the AJ population.

Current research: Research focuses on modifying the splicing defect in order to increase production of IKAP as well as to further understand the role of this vital protein. Researchers are also constructing an FD mouse model to further this aim. Clinical investigations include assessment of sleep physiology and assessment of molecular and functional biomarkers.