Home Page > Diseases by Region: Ashkenazi > Familial Dysautonomia (FD)

Familial Dysautonomia (FD)
by Yael Rosenberg, RN

• Description
• Symptoms
• Incidence and Carriers
• Treatment
• Testing
• Screening Laboratories
• Resources & More
• Support Groups

Description
Familial Dysautonomia (FD), a rare autosomal recessive genetic disease that results from mutation of the IKBKAP gene located on chromosome 9. The disorder affects the development and survival of certain nerve cells causing dysfunction particularly of the sensory and autonomic systems. The autonomic nervous system controls such involuntary functions such as breathing, swallowing, digestion, temperature and blood pressure regulation, as well as safe response to stress situations. The sensory nervous systems control reactions to pain, temperature and taste.

In general Familial Dysautonomia is a fatal disease, with approx. 50% of individuals reaching the age of thirty. Yet individuals affected by FD are usually of normal intelligence, and can be expected to function independently if treatment is begun early and major disabilities avoided

Symptoms
The usual function of the problematic gene is to produce a substance called dopamine beta-hydroxylase. A lack of beta-hydroxylase creates multiple problems

One of the most striking manifestations is the absence of overflow of tears with emotional crying. Though, keep in mind, it can be normal for a child not to have tears the first seven months of life. Severe eye problems are common because of the resulting dry eye and the absence of corneal response to foreign objects in the eye. Other signs of the disorder can be present from birth such as a high prevalence of breech presentation, weak or absent sucking ability, and poor tone.

Additional indicators include difficulties with swallowing, temperature regulation, blood pressure regulation, and feeding. Individuals with FD also suffer from seizures, are vulnerable to pneumonia, suffer from spine curvature (in 90% by age 13).

Approximately 40% of patients will have what is termed Dysautonomia Crisis. That is a group of symptoms in reaction to stress. In addition to vomiting, there is frequently increased heart rate and blood pressure, sweating, and a negative change in personality.
   •  Decreased response to pain and temperature
   •  Orthostatic hypotension (blood pressure drops when changing position i.e. standing up)
   •  Delayed developmental milestones
   •  Speech and lack of motor coordination
   •  Unsteady gait
   •  Labile blood pressure (fluctuating BP)
   •  Corneal anesthesia
   •  Marked sweating with excitement, eating or the first stage of sleep
   •  Breath-holding episodes
   •  Poor growth

Incidence and Carriers
Carrier Frequency: An estimated one in 30 Ashkenazi Jews, Unknown in the general population Disease Frequency: 1 in 3,800 in Ashkenazi Jewish population

Treatment
Treatment has had a dramatic impact on improving the prognosis of FD. Prior to 1960, approximately fifty percent of patients died before reaching the age of five. Nowadays, about half of the patients live to the age of thirty. The greatest impact on treatment has been the increased use of gastrostomy (surgical incision into the stomach) and fundoplication (mobilization of the lower end of the esophagus and subsequent folding of a portion of the stomach around it) to avoid aspiration pneumonia and to maintain adequate nutrition and hydration.

As there is still no cure for FD, treatments are symptomatic, as per the following:
   •  Artificial tears
   •  Special feeding techniques
   •  Special therapies (occupational, physical, speech)
   •  Special drug management of autonomic manifestations such as temperature regulation, blood pressure fluctuations, and digestive problems.
   •  Respiratory care
   •  Protecting the child from injury (coping with decreased taste, temperature and pain perception)
   •  Treatment of orthopedic problems (tibial torsion and spinal curvature)
   •  Compensating for labile blood pressures

Currently research in FD includes developing better treatment of orthostatic hypotension and better control of centrally induced nausea and vomiting. In the future, gene therapy may become an option.

Testing
Diagnosis is done by symptoms – absence of fungiform papillae on the tongue, diminished deep tendon reflexes, no overflow of tears with emotional crying.

Definitive diagnosis is made by genetic testing showing specific gene mutations.

Carrier genetic testing can detect the FD in 99% of Ashkenazi Jewish carriers.

EUROPE
   •  Germany
   •  Netherlands
   •  United Kingdom

GERMANY
bio.logis Center for Human Genetics
Frankfurt, Germany
Genetic Counselor: Prof Daniela Steinberger, MD, PhD
Phone: (+49) 695-308437
Fax: (+49) 695-308437-11
Email: Daniela.steinberger@bio.logis.de

Centogene GmbH
Schillingalee 68
18057 Rostock
Germany
Phone: (+49) 381-203652-0
Fax: (+49) 381-203652-19
Email: office@centogene.com

Diagenom GmbH
Robert-Koch-Str. 10
D-18059 Rostock
Germany
Phone: (+49) 381-7022750
Fax (+49) 381-7022759
Email: mail@diagenom.de 

NETHERLANDS
Academic Medical Centre, University of Amsterdam
DNA Diagnostics Laboratory
Amsterdam, Netherlands
Contact: Marcel M.A.M. Mannens, PhD
Phone: (+31) 20-5667899
Fax: (+31) 20-5669389
Email: kg_dna@amc.uva.nl


UNITED KINGDOM
Addenbrooke's Hospital
Molecular Genetics Laboratory
Box 158,
Level 6,
Addenbrooke's Treatment Centre,
Cambridge University Hospitals NHS Foundation Trust
Hills Road,
Cambridge,
CB2 0QQ
Phone: (+122) 3-348-866
Fax: (+122) 3-348-870
Becky Treacy FRCPath/Deputy Director Genetics Laboratories (Head of Molecular Genetics)
Phone: (+122) 3-348-801
Email: becky.treacy@addenbrookes.nhs.uk


Support Groups
Dysautonomia Foundation, Inc.
315 West 39th Street, Ste 701
New York, NY 10018
Phone: (212) 279-1066
Email: info@familialdysautonomia.org
Web: http://www.familialdysautonomia.org

Dysautonomia Genetic Counseling Center at the
Human Genetics Program
NYU School of Medicine
550 First Avenue, MSB 136
New York, NY 10016
Phone: (212) 263-5746
Fax: (212) 263-7590
Email: elsa.reich@med.nyu.edu
Center for the Study and Treatment of Jewish Genetic Diseases
at UPMC Health Systems
Contact: Erin O’Rourke, M.S.
Toll Free: (800) 334-7980
Email: eorourke@helix.hgen.pitt.edu

National Foundation for Jewish Genetic Diseases Inc.
250 Park Avenue, Suite 1000
New York, NY 10017
Phone: (212) 371-1030
National Foundation for Jewish Genetic Diseases Inc.
250 Park Avenue, Suite 1000
New York, NY 10017
Telephone 212-371-1030