Familial Dysautonomia

Familial dysautonomia (FD) is a rare, inherited disorder of the nervous system. It was first described in 1949 by Riley and Day and is therefore commonly referred to as Riley Day Syndrome.1

FD is extremely rare in the general population, but affects about 1 in 3600 babies born to couples of Ashkenazi descent.2 Although the prognosis has greatly improved, babies born with familial dysautonomia have only a 50% probability of surviving to age 40.2,3 This autosomal recessive disease affects the development and survival of autonomic and sensory neurons. As such, it affects many parts of the body, including the eyes. Throughout their lives, these patients will require regular visits to an eye doctor to monitor for ocular surface damage as well as neurological damage in other nervous structures in the eyes.

Visual impairment is almost always present in people with FD, which is attributable to damage to both the ocular surface as well as the structures in the back of the eye, such as the optic nerve.4 At the ocular surface, visual decline is typically attributed to the combination of dry eye and corneal aesthesia, which precipitate the formation of corneal abrasions and ulcerations that lead to scarring.5,6 It is important that the eyes of people with FD remain as moist as possible to prevent serious corneal damage.

What Causes FD?

Familial dysautonomia is an autosomal recessive disorder, which means that in order to develop the condition, you’d need to inherit a copy of the genetic mutation from both of your parents. It is caused by mutations in the IKB kinase-complex-associated protein (IKBKAP) gene. If you have only one copy of the mutation, you are considered a carrier—meaning you could pass it along, but won’t develop symptoms yourself.

Approximately 1 in 30 Ashkenazi Jews is presumed to be an FD carrier.7 If two FD carriers conceive, there is a 25% likelihood that their child will be born with FD. Carrier testing is available and is often encouraged.

How Is FD Diagnosed?

Familial dysautonomia is sometimes diagnosed soon after birth, when infants show signs of feeding difficulties or lack of tears at around 7 months of age. However, expression of the disease varies. As neurologic deterioration progresses with age, symptoms proliferate and the disease becomes more recognizable.

With respect to ocular health, people with FD have dry eyes resulting from lack of tears and decreased corneal sensation that can lead to injury and visual impairment. In some people, the optic nerve does not function normally.

Scleral Lenses for FD

A primary goal of treatment for people with FD is to maintain corneal moisture in an attempt to avoid dry eye complications. This is commonly achieved with the use of scleral lenses, which are often fit as soon as FD is diagnosed or if a corneal defect is present.

Scleral lenses are different from other contact lenses because they vault across the entire corneal surface and rest on the white part of the eye, known as the sclera. Liquid fills the space between your eye and the back surface of the scleral lens. This fluid-filled chamber protects the cornea from erosion, foreign insult and dryness—all of which commonly occur in people who have FD.

Other Ocular Treatments for FD

All of the currently available ocular treatments for FD are aimed at maintaining moisture and protecting the ocular surface.

People with FD are usually instructed to use preservative-free artificial tear products several times a day, along with ointments to be used at night. The use of autologous serum eye drops is another treatment option. These drops are made from components taken from the patient’s own blood and contain growth factors and vitamins that can help heal the ocular surface. Staying hydrated and avoiding environmental dryness is also advocated. Moisture chamber goggles can also be helpful, but are less necessary with the recent advancements in scleral lens treatment.

Prescription drops, such as steroids and cyclosporine A, are also frequently employed to reduce inflammation that can exacerbate dry eye. To minimize tear drainage, temporary or permanent closure of the tear ducts is commonly recommended.

In some cases, when ocular surface damage has already occurred, more aggressive strategies, including the use of amniotic membrane or tarsorrhaphy (surgical lid closure to narrow the eyelid opening in an effort to decrease the exposed surface area and prevent tear evaporation) may need to be employed.

If you have FD, visit your eye doctor to determine the most appropriate management strategy for you.

 


References:

[1] Riley CM, Day RL, Greely D, Langford WS (1949). "Central autonomic dysfunction with defective lacrimation". Pediatrics. 3 (4): 468–77. PMID 18118947.

[2] Gold-von Simson G and Axelrod FB (2006) Familial dysautonomia: Update and recent advances. Curr Probl Pediatr Adolesc Health Care 36:218-237.

[3] Axelrod FB, Goldberg JD, Ye XY and Maayan C (2002) Survival in familial dysautonomia: Impact of early intervention. J Pediatr 141:518-523.

[4] Mendoza-Santiesteban C, Hedges TR, Norcliffe-Kaufmann L, Warren F, Reddy S, Axelrod FB, Kaufmann H. Clinical Neuro-ophthalmic Findings in Familial Dysautonomia. Journal of Neuro-ophthalmology.2012. 32: 23-26

[5] Riley CM, Day RL, McGreeley D, Langford WS. Central autonomic dysfunction with defective lacrimation. Report of 5 cases. Pediatrics. 1949;3:468–477.

[6] Kroop IG. The production of tears in familial dysautonomia: preliminary report. J Pediatr. 1956;58:328–329.

[7] Dietrich P, Dragatsis I. Familial Dysautonomia: Mechanisms and Models. Genetics and Molecular Biology. Online ahead of print. 2016.