Panel of Experts’ Perspectives: Genetic Blindness: UDN 2016 – Irene Maumenee


Irene Maumenee:
And now can you put on the right one? I am here to proselytize for the integration of
geneticists with ophthalmologists. I think it will be of benefit for both of the groups
and I don’t think this integration has reached its maximum. I’m one of five of the [unintelligible]
in the U.S. who are board-certified in ophthalmology and in genetics so it’s a little bit the
Wild West out there. [laughter] How commonly do patients with genetic blindness
remain underdiagnosed or have a new disease? Undiagnosed — ophthalmologists miss Von Hipple-Lindau
syndrome disease; should certainly be obvious, but unless there is really massive disease,
ophthalmologists don’t get it. And they miss Fabry disease, misdiagnose the Leber’s
congenital amaurosis as intra-uterine infection, and under-diagnosed and unknowns — such common
diseases. The epilepsy of the ophthalmologist as open angle glaucoma. They are late-onset
diseases and affect two or three percent, but they clearly run in families. Age-related
macular degeneration, senile cataracts — are all in that group. How many genetic diseases with ocular involvement
are there? One quarter to one third of all genetic diseases are purely ocular or systemic
with ocular involvement, so it’s a tremendous impact. And if you go through [unintelligible]
and you read the report it’s just very clear that the numbers are very high. So there are
common diseases which may be clinically insignificant such as colorblindness, or the diseases I
mentioned before with late onset well after the era when people procreate, and there are
the rare diseases, and then there are new diseases. And an estimated two of ten percent
of patients remain undiagnosed after visiting an ophthalmologist. Obviously it’s a frustration.
It also obviously depends on who the ophthalmologist is, you see. I’m going to just say a few words about
a very rare disease, Leber’s congenital amaurosis, which is a disease where the retina
does not function from birth. And it affects about one in 50,000 to one in 100,000 newborns.
About twenty years ago a major effort was put into trying to identify the few expected
genes for this disease, and by now there are 19 solidly confirmed ones and another 11 where
there is sort of a single family, not confirmed in the second family, or the mechanism is
relatively unclear. And at present, when looking at the large series, 35 percent of patients
remain undiagnosed at the DNA level. So in spite of having a certainly significant number
of genes, there are still a lot of — there are still a lot of patients who are not diagnosed
at the appropriate level and for whom certainly treatment is at far away at the horizon somewhere.
The Leber’s congenital amaurosis is a disease in which one subtype, the RPE-65 mutation
group, have seen treatment approaches in the last ten years and have gained much notoriety
for it. If you look at the basic pathways that are
known for Leber’s congenital amaurosis they go all over the photoreceptors from vitamin
A cycle to photoreceptor development, but the large number are actually here in the
cilium and have similar features to the Body Betum syndrome for example, which is not part
of this disease scope. But most of those subtypes have at least one center that is interested
in developing treatment for the group and we are involved in creating and finding treatment
for patients with [unintelligible]-1 mutations. There is clear-cut progress thanks to a big
effort into identification of genes which are a causative for this devastating disease
of lifetime blindness. Where are the sources of identification — for
identification of undiagnosed patients and new diseases? Much progress in these diseases
has happened in the Middle East, in the countries in which there is a high rate of inbreeding,
and there are centers and people all know each other worldwide who work in this field.
And there has also been, close to the mainland U.S., a lot of progress in Puerto Rico looking
at Puerto Rican patients which has still a large impact of a founder effect in many centers
in which diseases are present there in the mountains and in various areas. Mechanisms of teaching. What has happened
in ophthalmology and genetics? There’s the ophthalmic genetic study club, which is in
its forty years of existence, and it is open and people come from all over the U.S. and
worldwide to participate in this one day where everybody shows their rare and unusual and
undiagnosed patients in order to see how this can be moved forward. That has gone into an
International Society for Genetic Eye Disease and Retinoblastoma which meets every two years.
The requirement of board certification and management of patients with genetic diseases
has to be seriously considered because everybody does it according to their interests. I think what needs to happen and what would
be great would be do a detailed geographic mapping using Geographic Information Systems
for patients and countries in order to move this forward. It’s already happening in
ophthalmology for Tacoma for, you know, basically other ophthalmic diseases, but not very seriously
for the genetic eye diseases. In summary, I have not touched on all of this,
but every part of the eye will show genetic diseases. There are thousands? Two thousand?
Who knows how many? Two thousand five hundred? So it goes from the front of the eye, from
the lens, from the lashes, from the cornea, conjunctivita — conjunctiva, lens, to the
retina and the optic nerve. Thank you. [end of transcript]

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