Introduction

Familial dysautonomia is a rare genetic disease. It is the most extensively described of the disorders known as hereditary sensory and autonomic neuropathies, a group of disorders which appear to affect development, survival and function of peripheral and central sensory and autonomic tracts (Axelrod & Pearson, 1984; Pearson et al., 1974). In the original report of familial dysautonomia by Riley et al. (1949), the disorder was called central autonomic dysfunction with defective lacrimation. Knowledge of the disorder has since expanded so that genetic transmission and pathophysiology are better understood and treatment programs have resulted in improved survival (Axelrod & Abularrage, 1982).

The gene is located on chromosome 9 (9q31) and in 2001 the two mutations causing familial dysautonomia were identified (Slaugenhaupt et al., 2001), which permits DNA diagnosis and general population screening. A de novo diagnosis, however, is based on clinical recognition of sensory and autonomic dysfunction (Table 33.1). It is expected that the following clinical criteria would be present in every affected individual:

1. Absence of fungiform papillae on the tongue and decreased taste (Smith et al., 1965b) (Fig. 33.1)

2. Absence of flare after intradermal histamine (Smith & Dancis, 1963) (Fig. 33.2)

3. Decreased or absent deep tendon reflexes (Riley, 1957)

4. Absence of overflow tears (Smith et al., 1965a).

To date, all individuals with a confirmed diagnosis have been of Eastern European Jewish extraction. Further supportive clinical evidence includes decreased corneal reflexes, decreased response to pain and temperature, postural hypotension, periodic erythematous blotching of the skin, and increased sweating.