Familial dysautonomia (Riley-Day syndrome)

The Familial dysautonomia, also known as hereditary sensory and autonomic neuropathy type 3 (HSAN3) or Riley-Day syndrome, is an inherited disorder characterized by sensory dysfunction and severe impairment of the autonomic nervous system, leading to a multisystem dysfunction.

The HSAN3 is almost exclusive to individuals of Eastern European Jew descent, with an incidence of 1 per 3,600 live births. It affects both sexes. The disease is transmitted as an autosomal recessive trait. The IKBKAP gene is located on the long arm of chromosome 9 (9q31). The diagnosis is based on clinical recognition of both sensory and autonomic dysfunction. The indicative criteria include alacrimia, lack of fungiform papillae, depressed patellar reflexes and abnormal histamine test.

Symptoms

The disease is present at birth and is progressive. Initial symptoms include swallowing problems, aspiration pneumonia, hypotonia, body temperature instability and developmental delay.

No obvious dimorphism is presented at birth, but eventually a characteristic facial expression may develop, serious kyphoscoliosis and short stature. The absence of tears with emotional crying is one of the main features of the disorder. Therefore, the first sign of autonomic dysfunction is normally feeding difficulty due to gastrointestinal dysmotility (alteration of oropharyngeal coordination, abnormal esophageal peristalsis, emptying erratic gastric, gastroesophageal reflux and episodes of attacks prolonged vomiting called 'dysautonomic crises''). There are also frequent chronic lung disease (as a result of repeated aspirations), restrictive lung disease (a consequence of scoliosis), muscle weakness and dysfunction chemoreceptors. It is common the presence of orthostatic hypotension without compensatory tachycardia. Patients may also experience episodic hypertension in response to emotional stress or visceral pain.

Negative personality changes range from irritability and withdrawal to general excitement. Forty percent of the patients manifest a cyclical crisis pattern with frequencies that can occur daily, weekly, or monthly and follows morning arousal. Pain and temperature perception are decreased, but not absent. Vibration sensation is normal. Deep tendon reflexes are decreased in almost all patients. Absent axon flare (following intradermal histamine) and lack of fungiform papilla on the tongue are characteristic features of HSAN3.

Gene or region studied

  • IKBKAP
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