Riley-Day syndrome

Definition

Riley-Day syndrome is an inherited disorder that affects nerve function throughout the body. Symptoms are present at birth and grow worse over time.

Causes, incidence, and risk factors

Riley-Day syndrome is inherited as an autosomal recessive trait, which means that a person must inherit a copy of the malfunctioning gene from each parent in order to develop the condition.

It is seen most often in people of Eastern European Jewish ancestry (Ashkenazi Jews), where the incidence is 1 in 3,700. The disease is caused by mutation of the IKBKAP gene on chromosome 9. It is rare in the general population.

Symptoms

• poor growth
• feeding difficulties
• breath holding
• sweating while eating
• long episodes of vomiting
• lack of response to painful stimuli
• seizures
• hypotonia, low muscle tone
• recurring bouts of fever
• recurring bouts of high blood pressure
• poor coordination - unsteady gait
• an unusually smooth tongue surface
• decreased taste
• diarrhea/constipation
• severe scoliosis
• skin blotching

Infants with this condition have feeding problems and develop pneumonia caused by breathing 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 (internal) pain, like menstrual cramps.

Intelligence is expected to be in the normal range.

Signs and tests

The diagnosis of Riley-Day syndrome is made through observing the signs and symptoms, and by molecular genetic testing of the IKBKAP gene located on chromosome 9. The detection rate (the number of existing cases that are identified) in the Ashkenazi Jewish population is >99%. Such testing is used for diagnosis, carrier detection, and prenatal diagnosis.

• Absence of axon flare response after intradermal histamine injection. (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
• Absence of overflow tears with emotional crying
• Tiny pupils after administering methacholine or pilocarpine into the eye
• Decreased deep tendon reflexes: In 95% of patients with FD, knee jerks cannot be elicited
• Parents of Ashkenazi Jewish ancestry

Treatment

Treatment may include:

• protection from injury
• treatment of aspiration pneumonia
• anticonvulsant therapy if seizures are present
• liquid tears and bethanechol to prevent drying of eyes
• anti-emetics may be used to control vomiting
• postural hypotension (low blood pressure when standing) can be managed with increased fluid and salt intake, caffeine, and waist-high elastic stockings

Expectations (prognosis)

With advances in diagnosis and treatment, survival continues to improve. Currently, a newborn with Riley-Day has a 50% chance of reaching age 30.

Complications

The following symptoms of "autonomic crises" occur in about 40% of patients:

• Excessive sweating of the head and torso
• Blotching of the face and torso
• Mottling of the hands and feet
• Hypertension (high blood pressure) and tachycardia (rapid heart rate)
• Nausea/vomiting
• Severe dysphagia/drooling
• Irritability
• Insomnia
• Worsening of muscle tone

Calling your health care provider

Call your doctor if symptoms change or worsen.

Prevention

Individuals of Eastern European Jewish background and families with a history of Riley-Day syndrome who are thinking of having children can seek genetic counseling to discuss risk and undergo testing where appropriate.

Genetic testing is very accurate for Riley-Day syndrome and may be used for diagnosis of affected individuals as well as for carrier detection and prenatal diagnosis.

Illustrations

Chromosomes and DNA

Page Content:

Familial dysautonomia; Hereditary sensory and autonomic neuropathy - type III ; familial dysautonomia