Finding the Hidden Tears in Familial Dysautonomia

In 1949, when pediatricians Conrad Riley and Richard Day first encountered 5 children unable to cry with tears, they knew they’d stumbled upon something quite unique. The syndrome they went onto report in the medical literature later became known as familial dysautonomia – the disease without tears.

Fast forward 68-years later and this no longer appears to be the case.

Human tears are produced in the lacrimal glands and secreted through ducts onto the surface of the eye. They contain oils and lubricants and flow continuously in response to chemical and irritant stimuli to keep the cornea clean and moist. These are known as reflex tears, and are released when the eye is exposed to wind, foreign bodies or irritating gases. Psychogenic crying – in response to emotional stress – appear to be unique to man and key to social bonding. Usually, infants begin shedding overflow tears within the first weeks of life. The parents Riley and Day encountered never saw their children weep in pain, sorrow or anger.

Tears are produced in the lacrimal glands. Crying with emotions is unique to humans. 

The lack of tears in patients with FD takes its toll on the eye. Without the liquid film on the surface, the corneas become injured by dust and debris, heal poorly, and become clouded by scars resulting in defects in the visual fields. Around 30% of patients with FD will lose their sight after repeated corneal abrasions.

When Dr. Horacio Kaufmann joined forces with Dr. Carlos Mendoza 5-years ago, they set out on a mission to better understand the eye problems facing patients with FD. Tear production was one of the areas vastly understudied.

Using a substance known as pilocarpine, they were able to show that the tear apparatus itself was intact. With pilocarpine drops, the tears could be drawn out of the lacrimal glands and released on to the surface of the eye. This meant that rather than a disease without tears, FD was a disease with hidden tears.

Now the team had to understand why patients with FD cannot cry.

Reflex tears are produced when the sensory receptors in the surface of the eye are excited. Using a special pen-like device, known as an esthesiometer, with nylon-tipped filaments they were able to measure the sensitivity of the cornea in patients with FD. What they showed was remarkable. Some patients had more sensitive corneas, were able to produce more basal tears, and had a thicker liquid film on the surface of the cornea.

“It all makes sense,” explained Dr. Kaufmann “the lacrimal glands are there and we can make them shed tears with drugs that we can deliver as eye drops”. Secretagogues – like pilocarpine – hold promise for the treatment for dry eye in FD.

What is still not apparent is why patients with FD don’t cry with emotions. The connections from the central nervous system that innervate the lacrimal system may not be fully developed.

The Paper: Mendoza-Santiesteban CE, Palma JA, Norcliffe-Kaufmann L, Kaufmann H. Familial dysautonomia: a disease with hidden tears. J Neurol. 2017 Apr 11. doi: 10.1007/s00415-017-8486-z. [Epub ahead of print] PMID:28401297

This work was supported by the Dysautonomia Foundation, Inc., a charity dedicated to improving the lives of families living with familial dysautonomia through research, clinical care and advocacy.

Dr. Alberto Palma was a recipient of the Poster Prize Award for this work at the American Autonomic Society International Congress in November 2016.