Familial dysautonomia (FD), also known as Riley–Day syndrome, is a rare, recessive genetic disorder of the autonomic nervous system FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies (HSANs). All HSANs are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.

Signs and symptoms

Signs and symptoms of familial dysautonomia usually commence during infancy and advance with age, and may include gastrointestinal dysmotility (including erratic gastric emptying, gastroesophageal reflux, abnormal esophageal peristalsis, oropharyngeal incoordination),/growth, delayed development (especially walking) and puberty (especially in girls), recurrent aspiration pneumonia (due to inhalation of food or vomitus)), hypotonia, enuresis, arrhythmias, hypertension (including episodic hypertension in response to emotional stress or visceral pain short stature, chronic renal failure (common), visual impairment, variable cognitive ability, characteristic facial features that develop with time, impaired vibration perception, lack of fungiform papilla of the tongue, A lower birth weight as compared to siblings, overflow tearing is absent in neonates and begins to appear only after 2–3 months of age

Prenatal testing

Familial dysautonomia is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, a 25% chance exists that the child will have FD. For pregnancies at increased risk for FD, preimplantation genetic diagnosis or prenatal diagnosis by amniocentesis (at 15–17 weeks) or chorionic villus sampling (at 10–14 weeks) is possible.

Management

No cure for FD has been identified. The only two treatment centers are at New York University Hospital and the Sheba Medical Center in Israel. One is being planned for the San Francisco area. Although the FD-causing gene has been identified and it seems to have tissue-specific expression, no definitive treatment exists at present.

A major issue has been aspiration pneumonia. Fundoplications (by preventing regurgitation) and gastrostomy tubes (to preclude oral nutrition) have reduced the frequency of hospitalization. Other issues that can be treated include FD crises, scoliosis, and various eye conditions due to limited or no tears.

Treatment of FD remains preventative, symptomatic, and supportive. FD does not express itself in a consistent manner. The types and severity of symptoms displayed vary among patients and even at different ages on the same patients, so patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and abnormal blood pressure. Common management strategies include artificial tears, appropriate feeding strategy (maintenance of adequate nutrition, avoidance of aspiration (thickened formula and differently shaped nipples for infants)), daily chest physiotherapy (nebulization, bronchodilators, and postural drainage) for chronic pulmonary disease, pharmaceutical management of autonomic features (e.g. intravenous or rectal diazepam, or rectal chloral hydrate), preventing accidental injury, prevention of orthostatic hypotension (hydration, leg exercise, frequent small meals, a high-salt diet, and medication (e.g. with fludrocortisone)), treatment of orthopedic problems, compensating labile blood pressure.

Parents and patients should be informed regarding daily eye care and early signs of corneal problems, as well as punctal cautery. Informing patients and caretakers has resulted in decreased corneal scarring and the need for more aggressive surgical measures such as tarsorrhaphy, conjunctival flaps, and corneal transplants.

Prognosis

The average age of death is in the third decade of life, but affected persons may live into their 70s.

Research

In January 2001, researchers at Fordham University and Massachusetts General Hospital simultaneously reported finding the genetic mutation that causes FD, a discovery that opens the door to many diagnostic and treatment possibilities. Genetic screening subsequently became available in 2001, enabling Ashkenazi Jews to find out if they are carriers.

Stem-cell therapy has been proposed as a potential future treatment. Eventually, treatment could be given in utero.

Research into treatments is being funded by foundations organized and run by parents of those with FD. No governmental support has been given beyond recognizing those diagnosed with FD as eligible for certain programs.

See also

  • Dysautonomia
  • Medical genetics of Ashkenazi Jews

References

Further reading

  • The Familial Dysautonomia Foundation