Clinical characteristics: Familial dysautonomia, which affects the development and survival of sensory, sympathetic, and parasympathetic neurons, is a debilitating disorder present from birth. Neuronal degeneration progresses throughout life. Affected individuals have gastrointestinal dysfunction, autonomic crises (i.e., hypertensive vomiting attacks), recurrent pneumonia, altered pain sensitivity, altered temperature perception, and blood pressure instability. Hypotonia contributes to delay in acquisition of motor milestones. Optic neuropathy results in progressive vision loss. Older individuals often have a broad-based and ataxic gait that deteriorates over time. Developmental delay / intellectual disability occur in about 21% of individuals. Life expectancy is decreased.
Diagnosis/testing: The diagnosis of familial dysautonomia is established in a proband with suggestive findings and biallelic pathogenic variants in ELP1 (formerly IKBKAP) identified by molecular genetic testing.
Management: Treatment of manifestations: Affected individuals are often managed by multidisciplinary specialists that include neurologists, physiatrists, orthopedic surgeons, physical and occupational therapists, speech-language pathologists, pulmonologists, cardiologists, nephrologists, ophthalmologists, dentists and dental hygienists, and social workers. Feeding teams manage neurogenic dysphagia; mental health professionals treat anxiety.
Surveillance: Routine monitoring of the following: weight, nutrition, safety of oral feeding, developmental/educational progress, mental status, pulmonary function, sleep-disordered breathing, frequency and severity of dysautonomic crises, blood pressure lability, vision and low vision needs, ataxia and activities of daily living, spine for scoliosis, dental care and needs; assessment of caregiver needs.
Agents/circumstances to avoid: The following can exacerbate symptoms: hot or humid weather; full bladder.
Pregnancy management: Pregnancies in women with FD are considered high risk because of blood pressure lability. Visceral pain related to contractions during labor is perceived normally; therefore, analgesia should be provided.
Genetic counseling: Familial dysautonomia is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an ELP1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the ELP1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible. Carrier screening is available on a population basis for individuals of Ashkenazi Jewish heritage.
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