OMIM ID:
Dysautonomia, Familial
Alternate Names
Defective Genes
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
Inheritance
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.