Familial Dysautonomia (FD) is a rare genetic disease that results from the abnormal development of the nervous system, particularly the sensory and autonomic systems.
What does Familial Dysautonomia mean?
Dys-auto-no-mia literally means the dysfunction of the autonomic nervous system. The autonomic nervous system controls involuntary functions, such as swallowing, temperature and blood pressure regulation. Individuals with FD cannot regulate these autonomic functions. In addition, they have problems in perceiving various sensations, such as pain and heat.
One of the most striking manifestations is the inability to produce overflow tears with emotional crying. Severe eye problems are common because of the resulting dry eye and the absence of corneal response to foreign objects in the eye. Many infants have an abnormal suck at birth and feeding difficulties may persist, resulting in poor weight gain, as well as repeated pneumonia due to misdirected swallows.
Other common manifestations are indifference to pain (including minimal or no response to bone fractures), inappropriate perception of heat and taste, excessive sweating, fluctuating blood pressures, gastrointestinal problems, poor speech and motor incoordination. Many children have stunted growth and scoliosis (curvature of the spine). Forty percent of the children are prone to repeated attacks of vomiting. Intelligence is usually normal. Some individuals with FD complete college programs and can be expected to function independently if treatment is started early and major disabilities are avoided.
Treatment has had a dramatic impact on improving the prognosis of this disorder. Prior to 1960, approximately 50% of patients died before five years of age. Currently, approximately 50% of patients reach 30 years of age. 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. Some other important treatment methods have been the use of diazepam and chloral hydrate to control intractable vomiting attacks, and artificial tears to supplement decreased eye moisture. In addition, blood pressure regulation is enhanced by giving extra fluid and salt, physical therapy and an anti-inflammatory medication known as fludrocortisone.
FD is inherited in an autosomal recessive manner and affects boys and girls equally. It only occurs in families of Ashkenazi Jewish descent. In 1993 researchers established that the gene for FD (referred to as DYS) is located on chromosome 9. In 1999, the location of DYS was narrowed to a very small region of chromosome 9, known as 9q31. In January of 2001, two research groups independently reported the identification of the DYS gene (also referred to as the IKAP or IKBKAP gene) on chromosome 9. Both groups found the same two gene mutations among the families that they studied. Of these two mutations, it appears that a single mutation accounts for over 99% of FD.
Until recently, carrier testing and prenatal diagnosis were only available for families with an existing history of FD. The research breakthroughs reported this year will make testing for such families more accurate and reliable, and have made it possible to offer highly accurate carrier testing and prenatal diagnosis for all couples of Ashkenazi Jewish ancestry, regardless of whether or not there is a previous family history of FD. One out of every 25 to 30 Ashkenazi (or Eastern European) Jews carries the most common Familial Dysautonomia mutation and one out of every 625-900 Jewish couples is at risk for having a child with FD. As 1 out of every 30 Ashkenazim is estimated to be a carrier of FD, carrier testing for the disease may soon become a standard part of screening programs. As a result of these recent findings, genetic testing to confirm diagnosis, predict carrier status, and identify affected pregnancies is now possible.
Symptoms of FD
Eyes: lack of overflow tears (dry eyes), corneal wounds (with poor healing), optic atrophy strabismus
Mouth: lack of fungiform papilla on the tongue, small jaw size with overcrowding of teeth & early tooth loss
Gastroentestinal: uncoordinated suck and swallow, episodes of cyclic vomiting, reflux (heartburn), motility problems (constipation, dumping syndrome)
Heart: episodes of erratic fast heart rate and high blood pressure, low blood pressure (hypotension), dysrhythmias
Lungs: Recurrent pneumonias due to aspiration, Inability to tolerate lower oxygen levels
Kidney: dehydration with elevated blood urea nitrogen (BUN), poor kidney blood flow, salt wasting, renal insufficiency or failure
Nervous system: autonomic dysfunction, decreased ability to feel pain or temperature, hypotonia, decreased deep tendon reflexes, ataxia and apraxia, “dysautonomic crisis” (episodes of erratic blood pressure, heart rate, cyclical vomiting, gaseousness, temperature instability, excessive sweating and salivation, anorexia, and apparent discomfort), seizures (due to breath-holding, febrile, and seizure disorders), dizziness, passing out
Orthopedics: scoliosis, kyphosis, exaggerated lordosis, neuropathic joints, inability to feel fractures
Skin: poor wound healing, blotching with eating, excitement, or sleeping, excessive sweatin (especially on the head)
Psychiatric: poor attention span, anxiety, depression, auditory processing problems, self-mutilation, separation anxiety
Obstetrical: breech presentation at birth, low birth weight, variable and late decelerations during labor, temperature instability in the newborn period
Development: delayed puberty, delayed gross motor and speech development
Miscellaneous: breath-holding (at end of expiration, person arches and stiffens, eyes roll back in the head, often can turn blue especially around the lips, passes out), poor weight gain, small stature