Familial Dysautonomia

Familial Dysautonomia Definition

Familial Dysautonomia (FD) is a disorder that affects the autonomic nervous system and causes developmental abnormalities of the sensory, sympathetic and certain parasympathetic neurons within the sensory and autonomic nervous system.

The condition is also known sometimes as Riley–Day syndrome or HSAN-III (Hereditary sensory and autonomic neuropathy type III).

Familial Dysautonomia Causes

FD occurs due to mutations in the IKBKAP gene on the chromosome 9 that does the encoding for IKAP protein. Three mutations in the IKBKAP gene have been identified in patients having Familial Dysautonomia. The most prevalent mutation causing FD occurs in the intron 20 of donor gene. The conversion of T—>C in the intron 20 of donor gene eventually led to a shift splicing which gives rise to an IKAP transcript that lacks exon 20. The translation of this particular mRNA gives rise to a truncated protein that lacks all the amino acids that are encoded in the exons 20-37. The G—>C conversion is another less prevalent mutation that leads to one amino acid mutation in 696, in instances where Proline replaces normal Arginine. The reduced amounts of the functional IKAP protein in the cells lead to Familial Dysautonomia.

Familial Dysautonomia Symptoms

FD can result in a number of symptoms, such as:

• Poor growth
• Insensitivity to pain
• Lack of tears while crying
• Labile blood pressure
• Postural hypotension
• Episodic hypertension

FD patients are frequently known to suffer from:

• Pneumonia
• Vomiting
• Respiratory difficulties
• Difficulties with movement and speech
• Difficulty in swallowing
• Unstable blood pressure
• Inappropriate perception of pain, heat, and taste
• Impaired Gastrointestinal motility

FD is not known to affect the intelligence of a patient.

The various symptoms of FD have been categorized into:

Eye problems

These include:

• Dry eyes or absence of overflow tears
• Optic atrophy
• Strabismus
• Corneal wounds showing poor healing

Gastrointestinal problems

These involve:

• Achalasia
• Reflux or heartburn
• Uncoordinated sucking and swallowing
• Episodes of cyclic vomiting
• Motility problems, like dumping syndrome and constipation

Mouth problems

These include:

• Early tooth loss
• Absence of fungiform papilla on tongue
• Small size of jaw with an overcrowding of teeth

Lung defects

These involve:

• Inability to tolerate low oxygen levels
• Recurrent occurrences of pneumonia due to aspiration

Heart abnormalities

These consist of:

• Dysrhythmias
• Hypotension or low blood pressure
• Episodes of high blood pressure and erratically fast heart rate

Kidney anomalies

These comprise of:

• Salt wasting
• Poor blood flow in kidney
• Renal insufficiency or renal failure
• Dehydration with elevated BUN or blood urea nitrogen

Nervous System problems

These include:

• Seizures
• Hypotonia
• Apraxia and ataxia
• Dizziness and fainting
• Autonomic dysfunction
• Febrile seizure or fever fits
• Reduced deep tendon reflexes
• Reduced sensations of pain and temperature
• Dysautonomic crisis, which includes symptoms like erratic heart rate and blood pressure, gaseousness, cyclical vomiting, temperature instability, anorexia, excessive salivation and sweating

Skin problems

These comprise of:

• Poor healing of wounds
• A tendency of excessive sweating
• Skin blotching with excitement, eating or sleeping

Orthopedic defects

These involve:

• Kyphosis
• Scoliosis
• Neuropathic joints
• Exaggerated lordosis
• The inability to feel one’s fractures

Psychiatric abnormalities

These include:

• Anxiety
• Depression
• Self-mutilation
• Separation anxiety
• Poor attention span
• Auditory processing problems
• Negative changes in personality

Developmental impairments

These comprise of:

• Delayed puberty
• Delay in the overall motor development and speech development

Obstetrical problems

These consist of:

• Low birth weight
• Breech presentation during birth
• Temperature instability during newborn period
• Variable or late decelerations at the time of labor

Other miscellaneous symptoms

These involve:

• Anemia
• Diarrhea
• Drooling
• Small stature
• Unsteady gait
• Breath-holding
• Spinal curvature
• Poor weight gain
• Corneal abrasion
• Red puffy hands
• Feeding difficulties
• Frequent lung infections
• Elevated DOPA:DHPG ratio

Familial Dysautonomia Diagnosis

While conducting the clinical diagnosis of FD, a doctor is likely to consider the following criteria:

• Both the parents are from Ashkenazi Jewish Background
• Decreased reflexes of the deep tendon
• Lack of overflow tears while emotional crying
• Absence of fungiform papillae on one’s tongue
• Muted response to intradermal histamine with the lack of axon flare
• Blood tests to check for IKBKAP gene
• Severe scoliosis
• Hypotonia in babies
• Repeated instances of high blood pressure

Prenatal testing for Familial Dysautonomia

FD is inherited in the autosomal recessive pattern, and so 2 gene copies in every cell are changed. If both the parents are found to be the carriers, the chances of the child developing FD will be 25%. Prenatal diagnosis for FD in pregnancies can be done by chorionic villus sampling at the stage of 10–11 weeks or by amniocentesis in between 14 to 17 weeks.

Familial Dysautonomia Treatment

At present, there are no definite curative options for FD. FD patients are found to die in 50% of all cases by the age of 30. The gene that causes FD has been detected and it is believed to have a tissue specific expression. There are only 2 treatment centers in the world where the patients of FD are treated; the New York University Hospital and Israel’s Hadassah Hospital. The survival rate of the patients and their overall quality of life has improved since mid 80s with better understanding of many life-threatening symptoms. Currently, early treatment can help to avoid major disabilities and enable FD patients to function independently.

Aspiration Pneumonias have been a major issue where the food or the regurgitated stomach contents get aspirated into the lungs and cause infections. Gastrostomy tubes and Fundoplications have proven useful in reducing hospitalization.

Some of the other curable conditions associated with FD include scoliosis, FD Crisis and various types of eye conditions caused by limited tears or lack of tears.

Treatment of FD is mostly preventative, supportive and symptomatic. The disorder is not expressed in a regular, consistent manner. The nature and severity of the symptoms vary from one patient to the other and even at different stages on same patients. Hence, it is necessary that the doctors develop specialized individual treatment plans for the patients. Medications are employed to control vomiting, blood pressure and eye dryness.

Some of the common ways of treating the symptoms of FD include the following:

• Using eye drops that contain methylcellulose or artificial tear solutions
• Maintenance of proper nutrition and using a thickened formula
• Avoiding aspiration and using differently shaped nipples for the baby
• Daily chest therapy should be conducted in order to monitor chronic lung diseases that are caused by recurrent aspiration pneumonia. Procedures will include nebulization, postural drainage and bronchodilators
• Controlling bronchial spasms
• Administration of special drugs like rectal chloral hydrate and rectal or intravenous diazepam for managing autonomic manifestations like vomiting
• Administration of anticonvulsant therapy to combat seizures
• Protecting an affected child from injury
• Helping a child to cope better with decreased sensations of temperature, taste and pain
• Dealing with orthostatic hypotension with usage of drugs like fludrocortisone, hydration, a diet with high salt content, frequent small meals, and leg exercises
• Treating orthostatic problems like spinal curvature and tibial torsion
• Dealing with labile blood pressures

Familial Dysautonomia Prognosis

The prognosis for FD patients varies with the diagnostic category. Those suffering from chronic, progressive and generalized Dysautonomia along with degeneration of central nervous system generally have a poor long-term prognosis. Severe pneumonia, sudden cardiopulmonary arrest or acute respiratory failure can cause death of such patients. However, the survival rate of FD patients has improved compared to earlier times due to technical advancements in diagnostic and treatment measures.

Familial Dysautonomia Complications

FD patients can suffer from the following complications:

• Excessive sweating of head and torso
• Blotching of face and torso
• Tachycardia or rapid heart rate
• Hypertension or high blood pressure
• Irritability
• Insomnia
• Drooling
• Mottling of hands and feet
• Vomiting and nausea
• Worsening of the muscle tone
• Dysphagia or severe difficulty in swallowing

Familial Dysautonomia Prevalence

FD occurs almost exclusively within the Ashkenazi Jews community and is extremely rare among the general population. Almost 1 in every 3700 individuals in the Ashkenazi Jewish populations are affected by this disorder.

Familial Dysautonomia Prevention

Individuals who have an Ashkenazi Jewish background or families having a history of this disorder should go for genetic counseling if they are planning to have children. This can help in evaluating the risks associated with this condition. Genetic testing is normally very accurate for FD and it can be employed for diagnosing the affected individuals, detecting the carriers and conducting prenatal diagnosis.

Familial Dysautonomia Pictures

Here are some pictures that show the patients who are having FD.

Picture 1 – Familial Dysautonomia

Picture 2 – Familial Dysautonomia Image

Familial Dysautonomia is a rare genetic disorder that essentially affects the Ashkenazi Jewish population. Serious complications from FD might even lead to the death of a patient. However, modern developments in medical science have improved the survival rates of patients and have enabled them to lead a normal life.