A panel of leading experts gathered
in Montreal last month to discuss the latest advances
in neurofibromatosis (NF) — a poorly understood
genetic disorder that results in the production of nerve
cell tumours — and to raise awareness about what
medicine can now offer patients afflicted with the disease.
When Dr Bruce Korf first entered
the field 25 years ago, management and treatment of
NF were virtually identical to what was being offered
60 years before, with the exception of better surgery
and better imaging. "Since then, the genes causing NF1
and NF2 have been identified, the cellular pathway involved
is understood, genetic testing has been developed and
is well established, and several clinical trials are
happening," says Dr Korf, chairperson of the genetics
department at the University of Alabama, Birmingham
and an internationally recognized authority on NF. "This
is a tremendous amount of progress, though more needs
to be done." The biggest challenge by far, he says,
has been getting news of that progress out to healthcare
professionals.
NEUROFIBROMATOSIS
101
NF encompasses three distinct autosomal dominant genetic
disorders — NF1, NF2 and Schwannomatosis. Each
type is characterized by the production of nerve sheath
(Schwann) cell tumours, causing a wide range of abnormalities
such as skin changes and bone deformities. Symptoms
are either apparent at birth or appear during infancy,
usually before age 10. Affected individuals may also
experience hearing loss, tinnitus and poor balance;
headache, facial pain or numbness caused by pressure
from the tumors can also occur.
Half of all cases of NF1 and NF2
are inherited from a parent, while the other half are
the result of a spontaneous mutation. The inheritance
pattern of Schwannomatosis, a much rarer disorder, is
not well understood, though it's believed to be mostly
due to spontaneous mutations of an as-yet-unidentified
gene.
There is no cure for NF. The disease
is managed through surveillance for treatable complications,
such as tibial dysplasia or mild scoliosis, while the
mainstay of neurofibroma treatment is surgery. But better
treatment is on the horizon. Several medical therapies
are currently being investigated, some of which have
entered the multi-centre trial phase.
According to the US Children's
Tumor Foundation, the main variant of the disease, NF1,
affects one in every 3,500 to 4,000 births. This makes
it the most common neurological disorder caused by a
single genetic mutation — as common as cystic fibrosis,
and more prevalent than hereditary muscular dystrophy,
Huntington's disease and Tay-Sachs disease combined.
But many still associate NF with Joseph Merrick, better
known as the "Elephant Man," whose diagnosis eluded
physicians for over 100 years. But Mr Merrick actually
suffered from Proteus syndrome, a totally unrelated
disease.
SPREADING
THE WORD
Dr Korf discussed a few of the most promising clinical
trials currently being conducted by the US National
Cancer Institute, The Children's National Medical Center,
and Mayo Clinic. They are investigating three drugs:
tipifarnib, a Ras (cellular growth protein) inhibitor;
pirfenidone, a fibroblast inhibitor; and AZD2171, an
angiogenesis inhibitor, respectively. "I personally
don't know that any of these trials will find the definitive
solution to this disease's many challenges. I see them
more as stepping stones as we move towards a cure,"
says Dr Korf. He believes the more immediate challenge
is getting accurate, up-to-date information about what
can be done now out into the open.
According to Dr Korf, the disease's
relative obscurity is due in large part to the way it
manifests. One of the most common effects are learning
disabilities, so families with a multi-generational
history of the disease often drift down into lower socio-economic
classes and are not articulate advocates for themselves.
"NF also creates an altered physical appearance, so
many people with the disease shun the kind of public
— and even medical — attention that might
otherwise help them," he says. In his experience, many
patients give up on treatment, feeling that short of
a cure, medicine has nothing to offer. "To help get
these patients actively involved in the management of
their condition, it's imperative to have them understand
that what they may have learned about NF, possibly decades
ago, is probably no longer true," he says.
Among the families where the parents
are unaffected, and their child's NF was spontaneous,
Dr Korf says the challenge is mainly getting them to
understand the spectrum of their child's condition.
"The manifestation of the disorder can vary widely from
individual to individual. When parents read about all
the very frightening effects of NF, it skews their view
of what's really going on with their child. We work
hard to put things into perspective." Likewise, Dr Korf
advises front-line physicians to work with experts,
whether locally or at a distance, for up-to-date information
and advice.
For more information about NF,
visit the Children's Tumor Foundation website: www.ctf.org.
For a copy of the bilingual educational video, "Emerging
from the Shadows (Sortir de l'ombre)," Contact l'Association
de la Neurofibromatose du Qu�bec: [email protected].
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