Familial dysautonomia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.

Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.

Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ELP1 gene cause familial dysautonomia. The ELP1 gene provides instructions for making a protein that is found in a variety of cells throughout the body, including brain cells.

Nearly all individuals with familial dysautonomia have two copies of the same ELP1 gene mutation in each cell. This mutation can disrupt how information in the ELP1 gene is pieced together to make a blueprint for the production of ELP1 protein. As a result of this error, a reduced amount of normal ELP1 protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of ELP1 protein, leading to the signs and symptoms of familial dysautonomia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Familial dysautonomia occurs primarily in people of Ashkenazi (central or eastern European) Jewish descent. It affects about 1 in 3,700 individuals in Ashkenazi Jewish populations. Familial dysautonomia is extremely rare in the general population.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal pupil morphology · Very frequent (99-80%)

An abnormality of the pupil.

Alacrima · Very frequent (99-80%)

The complete absence of aqueous tear production. Typically, this is clinically measured by a Schirmer I test result of 0 millimeters of wetting on the filter paper strip after 5 minutes.

EMG abnormality · Very frequent (99-80%)

Abnormal results of investigations using electromyography (EMG).

Feeding difficulties in infancy · Very frequent (99-80%)

Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.

Growth delay · Very frequent (99-80%)

A deficiency or slowing down of growth pre- and postnatally.

Hyperhidrosis · Very frequent (99-80%)

Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.

Hypohidrosis · Very frequent (99-80%)

Abnormally diminished capacity to sweat.

Hyporeflexia · Very frequent (99-80%)

Reduction of neurologic reflexes such as the knee-jerk reaction.

Other findings in the same source

From: Orphanet

Additional reported features include Impaired pain sensation (Very frequent (99-80%)); Malignant hyperthermia (Very frequent (99-80%)); Orthostatic hypotension (Very frequent (99-80%)); Peripheral neuropathy (Very frequent (99-80%)); Ataxia (Frequent (79-30%)); Atypical behavior (Frequent (79-30%)); Corneal erosion (Frequent (79-30%)); Gait disturbance (Frequent (79-30%)); Hypertension (Frequent (79-30%)); Hypotonia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Familial dysautonomia is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Familial dysautonomia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.