Familial dysautonomia (Riley-Day syndrome) in Children
Definition and Epidemiology
Familial dysautonomia (FD) is a rare genetic disorder characterized by autonomic nervous system dysfunction and sensory neuropathy. It primarily affects individuals of Ashkenazi Jewish descent, with a carrier frequency of approximately 1:32 in this population. The condition is caused by mutations in the IKBKAP gene (ELP1), inherited in an autosomal recessive pattern.
Clinical Manifestations
Autonomic Dysfunction:
- Cardiovascular instability
- Orthostatic hypotension
- Episodic hypertension
- Tachycardia
- Thermoregulatory dysfunction
- Temperature instability
- Hyperhidrosis
- Absence of fever during infections
- Gastrointestinal dysfunction
- Dysphagia
- Gastroesophageal reflux
- Recurrent aspiration
- Cyclic vomiting
Sensory Manifestations:
- Decreased pain and temperature sensitivity
- Absent corneal reflexes
- Impaired taste
- Absence of fungiform papillae on tongue
- Decreased deep tendon reflexes
Other Features:
- Developmental manifestations
- Growth retardation
- Delayed developmental milestones
- Learning disabilities
- Musculoskeletal features
- Scoliosis
- Kyphosis
- Joint deformities
- Ophthalmologic complications
- Corneal ulceration
- Optic nerve atrophy
- Strabismus
Diagnosis
Genetic Testing:
Molecular genetic testing for IKBKAP gene mutations is the gold standard for diagnosis.
Clinical Diagnostic Criteria:
- Major criteria:
- Ashkenazi Jewish descent
- Decreased deep tendon reflexes
- Absence of overflow tears
- Absent fungiform papillae
- Decreased pain perception
- Supporting features:
- Recurrent aspiration
- Skin blotching
- Postural hypotension
- Episodic hypertensive crises
Additional Diagnostic Studies:
- Intradermal histamine test
- Cardiovascular autonomic testing
- Swallowing evaluation
- Ophthalmologic examination
- Orthopedic assessment
Management
Multidisciplinary Approach:
Management requires coordination among multiple specialists:
- Neurologist
- Gastroenterologist
- Ophthalmologist
- Orthopedic surgeon
- Respiratory specialist
- Physical therapist
- Occupational therapist
- Speech therapist
- Genetic counselor
Specific Interventions:
1. Respiratory Management:
- Chest physiotherapy
- Postural drainage
- Prevention and management of aspiration
- Regular pulmonary function monitoring
2. Gastrointestinal Care:
- Feeding modifications
- Thickened liquids
- Postural adjustments during feeding
- Small, frequent meals
- Gastrostomy tube placement when indicated
- Anti-reflux measures
- Nutritional supplementation
3. Cardiovascular Management:
- Blood pressure monitoring
- Hydration maintenance
- Salt supplementation
- Compression stockings
- Medications for hypertensive crises
4. Ophthalmologic Care:
- Regular eye examinations
- Artificial tears
- Protective eyewear
- Monitoring for corneal complications
5. Orthopedic Management:
- Regular spine monitoring
- Bracing when indicated
- Surgical intervention for severe scoliosis
- Physical therapy program
Prognosis and Monitoring
Life Expectancy:
Variable, with many patients now surviving into adulthood with appropriate management. Major causes of mortality include:
- Respiratory complications
- Autonomic crises
- Cardiovascular events
Regular Monitoring:
- Growth and development tracking
- Regular assessment of autonomic function
- Monitoring for complications
- Assessment of quality of life
Long-term Complications:
- Progressive kyphoscoliosis
- Chronic respiratory insufficiency
- Renal involvement
- Cognitive impairment
References and Further Reading
Note: References should be verified and updated regularly as medical knowledge evolves.
- Axelrod FB, Gold-von Simson G. Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet J Rare Dis. 2007;2:39.
- Norcliffe-Kaufmann L, Slaugenhaupt SA, Kaufmann H. Familial dysautonomia: History, genotype, phenotype and translational research. Prog Neurobiol. 2017;152:131-148.
- Palma JA, Norcliffe-Kaufmann L, Fuente-Mora C, et al. Current treatments in familial dysautonomia. Expert Opin Pharmacother. 2014;15(18):2653-2671.
Note: This document is intended for medical professionals and should be regularly updated based on new research and guidelines. Clinical judgment should always be exercised in the management of individual patients.
