Familial dysautonomia

Familial dysautonomia (FD), also known as Riley-Day syndrome or hereditary sensory and autonomic neuropathy type III (HSAN III), is a rare inherited disorder that affects the development and survival of sensory and autonomic neurons. It is caused by pathogenic variants in the ELP1 gene (formerly IKBKAP) on chromosome 9q31.3. The disease predominantly affects individuals of Ashkenazi Jewish descent and is present from birth. The autonomic nervous system, which controls involuntary body functions such as blood pressure regulation, temperature control, tear production, and digestion, is severely impaired. Key clinical features include absence of overflow tears (alacrima), reduced or absent deep tendon reflexes, absence of fungiform papillae on the tongue, episodic vomiting crises (dysautonomic crises) with hypertension and tachycardia, postural hypotension, swallowing difficulties (dysphagia), aspiration pneumonia, decreased sensitivity to pain and temperature, progressive scoliosis, and labile blood pressure. Affected individuals may also experience excessive sweating, breath-holding episodes, and corneal damage due to decreased tear production and corneal insensitivity. Renal dysfunction can develop over time. There is currently no cure for familial dysautonomia, and management is supportive and symptomatic. Treatment strategies include careful feeding management to prevent aspiration, artificial tears and eye protection to prevent corneal ulceration, medications to manage dysautonomic crises (such as diazepam and clonidine), blood pressure management, orthopedic interventions for scoliosis, and chest physiotherapy for respiratory complications. Gastrostomy tube placement may be necessary for individuals with severe swallowing difficulties. Advances in supportive care have significantly improved life expectancy, though the condition remains associated with reduced lifespan. Research into therapies targeting ELP1 gene expression, including the use of small molecules such as kinetin (a plant cytokinin) to improve mRNA splicing, is ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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