Riley-day syndrome G90.1

Riley et al. 1949

Familial dysautonomy, also known as hereditary sensitive neuropathy type III, is a rare autosomal recessive hereditary disorder of the autonomic nervous system with disorders of tear secretion, increased saliva production, excessive sweating and lack of fungiform papillae of the tongue.

Prevalence: <1 / 1 000 000; the disease affects almost exclusively persons of Eastern European Jewish origin (Ashkenazi Jews) (Ramírez-Estudillo A et al. 2017): One in 30 Ashkenazi Jews is a carrier of the disease.

The cause are 3 (so far known) mutations in the ELP1 gene (syn: IKBKAP gene) which is located on chromosome 9 (9q31). This gene codes for the IKAP protein, a subunit of the RNA polymerase 2 elongator complex. The mutation results in a truncated unstable protein. ELP1 is involved in the migration, survival, and myelination of neurons during development. In humans, the mutation impairs the development of primary sensory and autonomic neurons.

The disease is manifest at birth and takes a progressive course. Initial symptoms (from birth to 3 years) are swallowing problems, aspiration pneumonia, muscle hypotension, unstable body temperature and delayed development.

Later, there is a lack of tear fluid (alacrimia), excessive sweating, lack of coordination of the digestive system, e.g. cyclic vomiting. Extreme blood pressure fluctuations may occur with tachycardia at short intervals (during these attacks there is an increase in circulating northern arenaine and dopamine) (Norcliffe Kaufmann LJ et al. 2013).

Hyp- and analgesia with no sensation of hot or cold can lead to severe burns and other injuries.

In addition, small stature, curvature of the spine, gait insecurity and speech difficulties are more common. Negative personality changes range from irritability and withdrawal to general states of arousal.

Dermatologically conspicuous are spot-shaped or generalized erythema, which tend to occur in attacks after meals and under stress, excessive hyperhidrosis, and the lack of fungiform papillae of the tongue.

Clinical findings; weakened patellar reflex, abnormal histamine test. Determination of the genetic defect.

A therapy of the genetic disorder is currently not possible. Symptomatic therapy. In cases of severe digestive tract miscoordination, such as frequent swallowing or cyclical vomiting (Norcliffe Kaufmann LJ et al. 2013), a PEG may have to be applied. The absence of tear fluid requires the regular administration of artificial tear fluid to prevent the eye from drying out.

The average age of death is in the third decade of life, but patients may reach the seventh decade of life.

Riley-Day syndrome belongs to the group of primary neuropathies (hereditary sensory autonomic neuropathies -HSAN-).

1. Norcliffe businessman LJ et al (2013) Cyclic vomiting associated with excessive dopamine in Riley-day syndrome. J Clin Gastroenterol 47:136-138.
2. Ramírez-Estudillo A et al (2017) Riley-Day Syndrome in a Hispanic Infant of Non-Jewish Ashkenazi Descent. J Clin Diagn Res 11:ND01-ND02.