Rare hereditary form of optic atrophy that usually
affects young males. Characterized by sudden bilateral cloudiness of vision,
followed by scotoma, rapid deterioration of central vision, and occasional
color vision disorders. Associated with atrophy of the optic nerve fibers
and retinae. Considered a mitochondrial disease. Cardiac conduction defects
have been reported with this condition.
Leber Disease; Leber Optic Atrophy.
NB: Do not confuse with Leber congenital amaurosis, another inherited
condition (without mitochondrial DNA involvement), resulting from a mutation in
the CRX gene.
Originally described by Theodore von Leber, a German Ophthalmologist, in the 19th century.
Incidence is not established, however, the disease is present
worldwide. Male predominance (2:1).
Genetic disorder related to mitochondrial DNA
transmission (i.e., exclusively from mother to child, either male or
female). At least four mutations in mitochondrial DNA (including G11778A,
T14484C, and G3460A) are associated with this clinical abnormality.
Different family pedigrees show different mutations but with clinically
similar pictures. The pattern of transmission within a kindred are not in
accordance with mendelian principles, and it is apparent that a complex
mechanism of inheritance is in operation. The disease is never transmitted
by affected men; it is transmitted by affected women or, most frequently, by
female carriers of the gene.
The mutation in mitochondrial DNA results in
lowering of the amount of energy available to the cells of the optic nerve
and retina, thus leading to severe cell damage. Fundal changes are described
as opacification of the disc margin, hyperemia of the disc vessels,
circumpapillary telangiectatic microangiopathy, and swelling of the
peripapillary nerve fiber layer.
Visual field testing reveals enlarging centrocecal
scotoma. Fluorescein angiography shows pseudoedema of the nerve fiber layer,
peripapillary telangiectasia, and increased tortuosity of the retinal
vessels. Pattern electroretinogram and visual-evoked potentials show optic
nerve dysfunction not associated with retinal disease. Magnetic resonance
imaging may reveal a high signal within the optic nerves. Molecular genetic
testing for the mutations can be decisive.
There is a wide spectrum of ages at onset of the
disorder. However, the most frequent age at onset is in the late teens. Typically, vision
fails from normal to severely impaired over a period of weeks, beginning
with one eye and then the other eye a few weeks later. Some improvement may
occur over months or years, however, vision is permanently impaired. There is
probably no association between this disorder and other organ systems. A
link between this and multiple sclerosis has been suggested but remains
unproved. Similarly, some patients have demonstrated both optic neuropathy
and cardiac preexcitation, but any link may be purely chance.
Thorough history and examination
should exclude any coexisting pathology. A 12-lead electroencephalogram should be performed
to exclude cardiac preexcitation or conduction defects.
No specific anesthetic techniques are
recommended or contraindicated. As with all neurologic conditions, it is