Familial dysautonomia, also known as Riley-Day syndrome, or FD, is an inherited disease that affects the sensory nervous system and the autonomic nervous system (responsible for regulating the function of most internal organs).
The autonomic nervous system regulates physiologic processes in our body, such as heart rate, respiration rate, blood pressure, body temperature, digestion, and blood flow to various organs.
The autonomic nervous system comprises two divisions: the sympathetic nervous system (mostly active in times of stress or danger), and the parasympathetic nervous system (activated in times of rest). These two systems work in coordination, to regulate nerve function throughout our body.
Familial dysautonomia belongs to a group of genetic diseases that affect the autonomic and sensory nervous system and is therefore referred to as “hereditary sensory and autonomic neuropathy type 3” (or HSAN3) in medical literature.
Genetic basis
Familial dysautonomia is a genetic disease inherited in an autosomal recessive pattern. This means that both parents must be carriers of the relevant gene mutation to have a child with this condition. Their chances for a subsequent pregnancy with a child with this disease are twenty-five percent.
This disease is only prevalent in people of Ashkenazi Jewish (eastern European) ancestry, and rarely occurs in the general population worldwide. The carrier frequency of FD among Ashkenazi Jewish people is 1 in 32, this frequency is even higher among Ashkenazi Jews from Polish descent.
FD is caused by a mutation of the IKBKAP gene, located on chromosome 9, that encodes the protein IKAP. It is not yet known why damage to this protein causes the disease to develop, nor is it known why this damage occurs primarily in the nervous system. The genetic impairment causes damage to the myelin sheath that is wrapped around the nerves. The myelin sheath plays an important role in conducting electrical signals in the nervous system.
Signs and symptoms
Shortly after birth, the first symptoms include feeding difficulties and a low muscle tone. Babies with FD develop gastroesophageal reflux with aspiration of gastric contents into the lungs and recurrent lung diseases.
Due to the deficiency in autonomic activity, people with FD suffer from an absence of tear secretion, vomiting and nausea. They also have unstable blood pressure, with a sudden drop or increase in blood pressure. Impairments to the sensory nervous system cause reduced sensitivity to pain and heat.
Autonomic crises
The most severe symptoms that occur in most patients are autonomic crises. These represent a temporary and severe instability of the autonomic nervous system. They can be triggered by physical and mental stress. During these crises, patients suffer from tachycardia, hypertension, respiratory tract secretions, and an inability to speak or swallow.
Diagnosis
The only definite diagnosis for this disease is through genetic testing. Ancillary tests can point to the existence of the disease, but not confirm it with absolute certainty.
Prenatal screening tests can help decrease the number of children born with this condition. These tests are recommended to couples of Ashkenazi Jewish ancestry who are planning on having children. Prenatal screening uses genetic markers linked to the mutated gene. Specific tests can help identify mutations known to run in the family.
Treatment
Unfortunately, there is no treatment for Familial dysautonomia, nor is the disease curable. Treatment is mainly supportive and symptomatic. Patients receive anti reflux treatment, chest physiotherapy, corneal abrasion treatment (due to a lack of tears), and more. Acute autonomic crises are treated with benzodiazepines with clonidine.
