Riley-Day syndrome is inherited as an autosomal recessive trait, which means that a person must inherit the defective gene from both parents in order to develop the condition.

It is found predominantly in people of European Jewish descent (Ashkenazi Jews). The disease is caused by mutation of the IKBKAP gene on chromosome 9. It is rare in the general population, but not amongst Ashkenazi Jews, where the incidence is estimated to be 1 in 3,700 people.

Infants with this condition have feeding problems and develop pneumonia caused by breathing their formula and food into their airways. Vomiting and sweating spells begin as the infant matures. Young children may also have breath-holding spells that produce unconsciousness, since they can hold their breath for long enough to pass out without feeling the discomfort that normal children would.

A hallmark of Riley-Day syndrome is insensitivity to pain. This leads to unnoticed injuries or injuries that might not have occurred had the child sensed discomfort. Children do not feel the normal sensations that generally warn of impending injury, such as drying of the eyes, pressure over pressure points, and chronic rubbing and chaffing. Bone and skin pain, including burns, are also poorly perceived. However, they can feel visceral pain, like menstrual cramps.

Seizures occur in almost 50% of affected children. They have acute problems with high and low blood pressure. They may have problems regulating their body temperature.

• a family history of Riley-Day syndrome
• Ashkenazi Jewish heritage
• feeding difficulties -- poor sucking and poor ability to swallow, drooling
• breath holding
• sweating while eating
• protracted episodes of vomiting
• lack of response to painful stimuli
• seizures
• hypotonia, low muscle tone
• abnormal body temperature (high or low)
• abnormally high blood pressure occurs intermittently
• incoordination, unsteady gait
• an unusually smooth tongue surface (due to absence of fungiform papillae)
• severe scoliosis

DNA testing can be done by linkage analysis or direct mutation testing. However, the formal diagnosis of Riley-Day is based on observations, not genetic testing. The signs are:

• Evidence of recurrent aspiration pneumonia on an X-ray of the chest
• Cyclic vomiting
• Unsteady gait
• Damage to the eye due to lack of tearing and blink reflex; gently touching the cornea of the eye with a "Q-Tip" won't produce a blink
• Absence of flare response to histamine. (Normally, when histamine is injected just under the skin there will be swelling and redness. If there is a lack of this flair response, the test is positive and indicates Riley-Day syndrome.)
• Absent or decreased deep tendon reflexes
• Insensitivity to pain or burns
• Speech abnormalities
• Normal intellect
• Delayed puberty
• Short stature
• Abnormal heart rhythm on ECG
• Absence of overflow tears
• Tiny pupils after administering pilocarpine into the eye
• Postural hypotension
• Blotching
• Increased sweating

Protection from injury is critical. Problems are treated as they occur, including treatment of aspiration pneumonia, anticonvulsant therapy if seizures are present, and liquid tears and bethanechol to prevent drying of eyes.

Anti-emetics may be used to control vomiting. Postural hypotension can be managed with increased fluid and salt intake, caffeine, and waist-high elastic stockings.

An annual spine exam is needed to monitor for scoliosis, which can be treated with braces or surgery.

• Charcot joints from repeated injury
• Increased risk of diabetes
• Phobias and emotional disorders (depression and anxiety)
• Renal failure in early adulthood