Sandy:

In our family each generation got worse too.

Jenn

--- Sandy Chasse <slchasse@...> wrote:

> Nice article but,,IMHO ..it states that each
> generation is not as affected as the next is how I
> understtod it ..BUT in my families case each
> generation got worse ...Sandy
> ----- Original Message -----
> From: ~Becky M.~
> To: CMT-Support
> Sent: Tuesday, October 02, 2007 11:51 AM
> Subject: [CMT-Support] National Foundation for
> Peroneal Muscular Atrophy (CMT)
>
>
> Sent by Dawn, thank you Dawn. :-) This is an older
> article, but very interesting to read.
>
http://users.rcn.com/smith.ma.ultranet/files/Dyck.discusses.CMT.txt
> This article is reprinted from The NFPMA Report
> published by the Charcot-Marie-Tooth
> Association with their permission.
> The CMT Association was previously called The
> National Foundation for Peroneal
> Muscular Atrophy (NFPMA)
>
> The CMT Association
> Crozer Mills Enterprise Center
> 601 Upland Avenue
> Upland, PA 19015
> Telephone 610-499-7486
>
> ------------------------------
> National Foundation for Peroneal Muscular Atrophy
> The NFPMA Report
>
> Winter 1989
> Vol. 3/No. 1
>
> Providing information on Charcot-Marie-Tooth
> disease (or Peroneal Muscular Atrophy),
> the most common inherited neurological disease
>
> DR. PETER JAMES DYCK DISCUSSES CMT
>
> The following article is excerpted from the
> keynote address Dr. Peter James Dyck gave at
> the Second International Conference on
> Charcot-Marie-Tooth disorders in June, 1987.
> The conference was sponsored by the NFPMA and
> Columbia University. (See The
> NFPMA Report, Vol. 1, #3.) Dr. Dyck, a world
> recognized authority on CMT, is a
> professor of neurology, a researcher, and a
> clinician at Mayo Medical School, Rochester,
> Minnesota. He has authored or co-authored 290
> clinical and research articles. Since Dr.
> Dyck's audience primarily included research
> scientists, much of his speech was of a
> technical nature. However, parts of it were of
> such a nature that we felt every CMT
> patient should have the opportunity to benefit
> from Dr. Dyck's insights and advice to
> physicians and patients.
>
> My interest in inherited neuropathy began in 1962.
> I began to see patients in a valley of
> the Mississippi River, the Zumbro River, which
> flows into Lake Pepin. This kindred
> lived in the small villages and farms of that area
> and it turned out that investigators from
> the University of Minnesota had done genetic
> studies in this region some fifty years
> earlier.
>
> I pursued Ed Lambert's discovery of low nerve
> conduction in inherited neuropathy. We
> now know much more about inherited neuropathy than
> we did twenty-five years ago.
> Some of you here have played important roles in
> these discoveries. Unfortunately much
> more remains to be discovered about inherited
> neuropathy. When we began our studies
> the question was why are conduction velocities low
> in inherited neuropathy? Lambert had
> made the observation that they sometimes were low,
> and secondly that they might serve
> as a marker of Charcot-Marie-Tooth syndrome. We
> asked a series of questions. Why
> was nerve conduction low? Did all kindreds with
> peroneal muscular atrophy have such
> low nerve conductions? Are the nerves enlarged in
> peroneal muscular atrophy? Why?
> Since nerve has fibers of different functional and
> size classes, which classes were
> especially vulnerable to disease? Was the neuron,
> or the axon, or the Schwann cell, or the
> myelin selectively involved? What were the three
> dimensional alterations along the nerve
> fiber? We also asked what was the metabolic
> abnormality in these diseases? Were the
> syndromes with peroneal muscular atrophy
> distinctly different? Were they from different
> mutant genes? What was the role of environmental
> factors? What were the gene loci
> (chromosome locations)? Are there specific
> treatments in these disorders? The reason
> for listing these questions is to show that
> progress has been made in the last twenty-five
> years. We have answers for many of these
> questions.
>
> Since I began my studies in inherited neuropathy
> we have learned a lot. We know that
> peroneal muscular atrophy is not one disease but
> several diseases. We have learned a
> considerable amount about how the disorders can be
> detected and characterized. The
> disorders known as Charcot-Marie-Tooth syndrome
> may also be referred to as forms of
> Hereditary Motor and Sensory Neuropathy, or HMSN.
> Some are directly inherited from
> an affected parent to one-half of the children
> (dominantly inherited). Others are
> recessively inherited (25% of the children from
> unaffected parents) and still others are
> inherited (sons) from an unaffected mother
> (sex-linked). There are different disorders
> even within these different inheritance patterns.
> Low nerve conductions are a useful
> marker for some disorders but not for others. The
> approximate chromosome and gene
> localization is known for two varieties of HMSN,
> HMSN-lb and sex linked HMSN.
>
> We now have some understanding of the structural
> changes in nerve which account for
> the clinical symptoms and abnormality of nerve
> conduction. In HMSN-1 all classes of
> nerve fibers are affected. There is an abnormality
> of redistribution of enzymes and other
> macromolecules along the length of the fiber. The
> nerve fiber appears to develop
> normally, then prematurely begins to atrophy. This
> atrophic condition appears to begin in
> the feet and legs. With atrophy there is myelin
> remodeling. Repeated de- and
> remyelination is involved in developing a
> microscopic abnormality called the onion-bulb
> formation and enlargement of the nerve. Disturbed
> electrical phenomena are associated
> with fiber atrophy and myelin re-modeling.
>
> Low nerve conductions, in general, relate to the
> severity of the clinical deficits. The
> evidence for myelin remodeling and for the
> occurrence of secondary demyelination also
> came from studies of uremic neuropathy,
> Friedreich's Ataxia (a recessively inherited
> disorder also associated with peroneal muscular
> atrophy) and an experimental study of
> the nerves above the site of the amputation of the
> legs in cat and man.
>
> Several lines of evidence convinced us that
> demyelination (breakdown of the fat and
> protein insulation of a nerve fiber) could, in
> some cases, be due to axonal atrophy. The
> reasons were: (1) demyelination was clustered on
> certain fibers-presumably those with
> atrophic axons, (2) demyelination was more
> frequent in more proximal aspects of nerve-
> distally fibers had undergone degeneration, and
> (3) in transverse sections of nerve the
> caliber of axons relative to myelin thickness was
> decreased as compared to normal.
>
> To prove our hypothesis we amputated legs of cats
> and evaluated nerve fibers above the
> amputations at various times after injury. Even by
> four months the frequency distribution
> peaks of myelin fiber diameters had shifted to
> smaller diameter categories. By one year
> this atrophic trend was clear. By two years the
> findings were very striking; an atrophic
> process had occurred. We could reproduce all of
> the changes that we had seen in uremic
> nerves. After injury the following sequential
> changes had taken place: axonal atrophy,
> myelin wrinkling, paranodal or internodal
> demyelination, remyelination, and with further
> atrophy axonal degeneration. Our model had proven
> what we had suspected from the
> human observations. Axonal atrophy may cause
> myelin remodeling.
>
> A new insight which has come from our recent
> studies is the important role of
> environmental factors in the clinical
> manifestations of HMSN. This should not have been
> a surprise since it was already clear from both
> experimental study and human neuropathy
> that environmental factors do play a role in the
> expression of mutant genes. For example,
> in porphyria the clinical disorder is not
> expressed
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