Fatal Familial Insomnia
by: Ann M. Akroush
Fatal familial insomnia is a genetic disorder. It manifests itself by many
symptoms due to the degeneration of a certain part of the brain, the thalamus.
The disease also results in the formation of amyloid plaques. This is the
build up of a waxy substance made of proteins associated with polysaccharides.
The disease is a result of a mutation of a normal protein that is associated
with brain tissue. This is the prion protein. In the case of fatal familial
insomnia, the mutation occurs 178 amino acids into the normal protein. Were
an asparagine should be, an aspartic acid is instead. This disease is an
autosomal dominant, which means that both sexes are affected and there are
no carriers. If an individual inherits the mutant gene, that individual
will at some point suffer the disease.
In the case of fatal familial insomnia, the affected area of the brain is
the area responsible for sleep, the thalamus. The thalamus is the center
which communications from the brain to the body and the body to the brain
pass through for proper directions to where a signal should be received.
When sleep takes place, it is thought that the thalamus becomes less efficient
at this signal transfer function allowing for the vegetative state of sleep
to come over an individual. Consequently, the symptoms of fatal familial
insomnia are directly related to the malfunction of the responsibilities
of the thalamus, namely sleep. Sleep, blood pressure, heart rate, body core
temperature and hormone flow are all affected by the interruption of the
body's circadian rhythms which is a direct result of the degeneration of
the thalamus in this disease. Other symptoms of this disease include the
inability to produce tears or feel pain as well as poor reflexes and dementia.
The lack of sleep leads to other problems such as hallucinations and coma.
This is a clear demonstration of a pleiotropic disease, a disease with many
phenotypic expressions. That is, this disease is the result of one mutant
gene yielding one mutant protein, yet causes many physical abnormalities
such as skin blotches, lack of tears, etc.
In the case study of an Italian family where of 288 relatives over 6 generations,
29 are affected by the disorder. The average age of onset of the disease
is 49, but this may vary with the individual as with one female who was
61 years of age. Her disease lasted 18 months and followed the following
pattern of the disease.
There are four stages of the disease before an individual's life ends. The
first stage is progressive insomnia, the trade mark of fatal familial insomnia.
The first stage develops over approximately four months and includes a collection
of psychiatric problems such as panic attacks and bizarre phobias. The second
stage includes hallucinations, panic, agitation and sweating and lasts about
five months. The third stage lasts about three months and is total insomnia
with weight loss. The individual at this point looks much older and may
experience incontinence. The fourth stage is around six months long and
is recognized as dementia, total insomnia and sudden death after becoming
This disease does not show until or past child bearing years when potentially
affected individuals may have already had children that may also be potentially
affected. Because of this fact, modern biotechnology must be employed for
early diagnosis. Techniques such as DNA sequencing or molecular hybridization
with a probe which seeks to detect the defective gene may be used for early
As for the treatment of this disease, hope may be found in the advancement
of something called gene therapy. This treatment involves the insertion
of the correct gene into an affected individual altering his/her gene expression
making it what it should be for the expression of the correct protein. In
order for this to happen, early diagnosis of an individual must be accomplished,
possibly by the mentioned biotechniques above. This is so that the defective
gene may be repaired before the onset of the disease. In order for this
to be possible, the corrective gene must be isolated. Furthermore, the corrective
gene must be good for transfer as well as a the proper vector to effectively
execute the transfer. Because there is no cure for this illness, gene therapy
may be the only answer if it is one day successful.
Guilleminault, C., Lugaresi, E., at el. Fatal Familial Insomnia: inherited
diseases, sleep, and the thalamus. Raven Press, 1994. pp.15-20.
Klug, W.S., Cummings, M.R. Concepts of Genetics. Prentice-Hall, Inc., 1994.
Medori, R., Tritschler, H-J., at el. "Fatal Familial Insomnia, a Prion
Disease with a
Mutation at Codon 178 of the Prion Protein Gene" New England Journal
Medicine, 326 (7): 444-449 (1992).
Petersen, R.B., Tabaton, M., at el. "Analysis of the prion Protein
gene in Thalamic
Dementia" Neurology, 42 (10): 1859-1863 (1992).
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