Familial dysautonomia

Muscle Nerve. 2004 Mar;29(3):352-63. doi: 10.1002/mus.10499.


Familial dysautonomia (FD) is a neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies, each caused by a different genetic error. The FD gene has been identified as IKBKAP. Mutations result in tissue-specific expression of mutant IkappaB kinase-associated protein (IKAP). The genetic error probably affects development, as well as maintenance, of neurons because there is neuropathological and clinical progression. Pathological alterations consist of decreased unmyelinated and small-fiber neurons. Clinical features reflect widespread involvement of sensory and autonomic neurons. Sensory loss includes impaired pain and temperature appreciation. Autonomic features include dysphagia, vomiting crises, blood pressure lability, and sudomotor dysfunction. Central dysfunction includes emotional lability and ataxia. With supportive treatment, prognosis has improved greatly. About 40% of patients are over age 20 years. The cause of death is usually pulmonary failure, unexplained sudden deaths, or renal failure. With the discovery of the genetic defect, definitive treatments are anticipated.

Publication types

  • Review

MeSH terms

  • Autonomic Nervous System / pathology
  • Autonomic Nervous System / physiopathology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Dysautonomia, Familial / genetics
  • Dysautonomia, Familial / pathology*
  • Dysautonomia, Familial / physiopathology*
  • Humans
  • Nerve Fibers, Unmyelinated / pathology
  • Neurons, Afferent / pathology
  • Peripheral Nerves / pathology
  • Peripheral Nerves / physiopathology*
  • Prognosis
  • Transcriptional Elongation Factors


  • Carrier Proteins
  • Elp1 protein, human
  • Transcriptional Elongation Factors