IKBKAP

Dysautonomia, Familial

Clinical Characteristics
Ocular Features: 

Decreased lacrimation is the major ocular feature in this syndrome and it may be sufficiently severe to result in corneal damage.  Decreased corneal sensation as part of the generalized neuropathy likely plays a role.  Epithelial defects are slow to heal and their chronic presence along with neurotrophic ulcers often leads to corneal thinning.  The blink rate is reduced, especially during crises.  The lid fissures are abnormally wide contributing further to corneal drying.  The pupillary light response time may be prolonged.  Miosis follows administration of methacholine chloride.  Optic neuropathy with pallor is often present.

Systemic Features: 

Vasomotor instability and sensory neuropathy are among the outstanding signs in familial dysautonomia.  Episodic hypertension alternating with hypotension, hyperhidrosis, cyclic vomiting, and skin blotching are common.  Deep tendon reflexes are often diminished or absent and there is a general indifference to pain and temperature.  The lingual fungiform papillae are missing resulting in taste disturbances.  Emotional instability and impaired coordination are frequently seen.  Emotional or physical stress can precipitate dysautonomic crises with nausea, vomiting, agitation, tachycardia, and hypertension.  Physical growth may be slow and scoliosis is common.  Patients are susceptible to self-injury.

Arrested development in the sensory and autonomic nervous systems results in a reduction in nonmyelinated nerve fibers as well as a reduction in small diameter myelinated axons.  Sympathetic ganglia are abnormally small in size.  There is hypersensitivity to both sympathomimetic and parasympathomimetic drugs.

Genetics

Hereditary sensory and autonomic neuropathy type III results from mutations in the IKBKAP gene (9q31).  It is an autosomal recessive condition.

A brief report describes 4 sibs with a clinical picture similar to familial dysautonomia with a mutation in DST (6p12.1).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the general disease but therapies are available for specific problems.  Good hydration, assisted ventilation during sleep, and liberal use of tear substitutes can be helpful.  Lacrimal ointments and lid taping during sleep are advised.  Punctal occlusion should be considered in selected cases.  Corneal ulcers or slow healing epithelial defects can be treated with a temporary tarsorrhaphy.   

Patients with familial dysautonomia are at increased risk of intraoperative cardiorespiratory complications which can be reduced by adequate hydration, reduced use of volatile anesthetic agents, and attention to postoperative ventilation.

References
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