Andrew Peake
*******Disclaimer*******
The information contained in this web page is not intended to diagnose
or prescribe
treatment for any form of myasthenia, and should be used for education
purposes only.
The information presented is based on what I have learned from my experiences
as a father
of 2 children (son 12 yrs old, daughter 6 yrs old) diagnosed
with congenital myasthenia.
My son was misdiagnosed for over 6 years as having a metabolic disease.
Information about congenital myasthenia is hard to find, so I am attempting
to compile a
useful set of information for others in need of this..
Decisions on diagnosis and treatment should be made by a physician.
*******Disclaimer*******
The Congenital Myasthenic Syndromes (CMS) consitiute a group of rare
genetic disorders
affecting neuromuscular transmission. They differ from myasthenia gravis
and the Lambert-Eaton
myasthenic syndrome, which are autoimmune antibody mediated conditions.
Over 12 variants of CMS have been identified, several which have been
partially characterized.
The congenital myasthenias cause clinical symptoms (muscle weakness
and fatigability)similar to the more
common autoimmune caused disease myasthenia gravis (MG).
The onset of symptoms of CMS usually present with in the first 2 years
of life.
There is a form of myasthenia know as neonatal myasthenia, this is
passed on to a new born
infant of a myasthenic (autoimmune caused) mother. This should be distinguished
from CMS.
Classifications of congenital myasthenic syndromes:
Presynaptic defects
- Defects in ACh resynthesis or packaging (aka familial infinitile
myasthenia)
- Paucity of synaptic vesicles and reduced quantal release
Synaptic defects
- End-plate AChE deficiency
Postsynaptic defects
- Kinetic abnormalities of AChR and AChR deficiency
- Slow channel syndromes (several types)
- Plus many others
Click here for more detailed descriptions
Myasthenic
Syndromes
For a very technical detailed report on CMS, obtain an article titled
"Congential
Myasthenic Syndromes" written by Dr. Andrew Engle of the Mayo clinic.
This was published in "Neurologic Clinics of North America", volume
12, number 2, May 1994.
CMS symptoms are:
1. Poor sucking/feeding ability
2. Respiratory distress/crisis
3. Ptosis (droopy half open eyes)
4. Opthalmoplegia (floating/waundering eyes)
5. Limited range of movement in eyes (up/down/side ways)
6. Delayed gross motor development (varies greatly for each CMS patient)
7. Dysphagia (swallowing problems)
One of the confounding problems with CMS is that the severity of symptoms
can range dramatically. Some
patients with CMS may have all of these symptoms and be very impaired,
while another may have only a few symptoms and the degree of their
impairment may hardly
be noticable. It is common to have siblings that are also affected
with CMS.
Repiratory crisis can be one of the worst problems of CMS, if a patient
is unable to maintain a cleared airway
(usually agravated by respiratory illness) it is sometimes neccessary
for a
trachetomy to be performed to assist adequate breathing.
Fever inducing illnesses seem to adversely affect CMS patients the
most, it is not uncommon
for a child to become very lethargic and limp (rag doll like) and require
medical intervention.
It is very difficult to get a proper confirming diagnosis for CMS, most
Neurologist may not be
aware of it, as it is extreemly rare. Very little if anything at all
is mentioned on CMS in standard medical text.
The standard "tensilon test" used to help diagnose MG, is
unreliable for diagnosing CMS and should not be used to prove/disprove
CMS.
The occurance of CMS is reported to be 1 or 2 per million.
CMS is not as uncommon as reported -- but it is common to misdiagnose
it.
Often a diagnosis of "unspecified muscle myopathy" is made to account
for the
symptoms of weak muscles and fatigability.
Testing required to solidly diagnose CMS:
1. Electromyography (EMG), a repetitive nerve stimualtion (RNS) test
is done on specific
nerves to determine if there is abnormal fatiguing
(degredation response) at the
the nerve muscle junction (NMJ).
2. Serum antibodies testing to screen for autoimmune causation.
Note: there is a form of myasthenia known as seronegative,
in which antibodies are
not detectable. In the case of CMS antibodies
will not be present since this form of
myasthenia is genetically caused.
3. Specialized muscle biopsy in which an intact muscle (bone to bone)
is removed and
used to do electrophysiologic testing to determine
the site of defect in the NMJ.
There are only 2 centers in the United States which
perform this specialized form of biopsy.
The muscles commonly used are the anconeus and the
intercostal , the centers are the
Mayo Clinic in Rochester Mn. and the University
California Davis in Sacramento Ca.
Therapies for CMS are limited:
1. Mestinon is the first line treatment. Mestinon seems to work the
best when the defect at the
NMJ is post synaptic (like with autoimmune caused
myasthenia gravis).
Mestinon is known as an anticholinesterase drug
which helps inhibit the break down of
acetylcholine. Some CMS patients will not respond
to mestinon.
2. Ephedrine sulfate is also used as a therapy for CMS. This drug was
used for decades
to treat myasthenia gravis before the advent of
steriod drugs.
It is believed that ephedrine provides beneficial
effects to muscle function at a level remote
from the NMJ. Other adrenergic drugs, like albuterol
are some times substituted.
The down side of ephedrine is that some patients
build up a tolerance to it and may need to
take periodic breaks to aid in restoring its effectivness.
3. 3,4 Diaminopyridine (3,4 DAP). This drug has been used to treat
Lambert Eaton
myasthenic syndrome (LEMS), a presynaptic form of
myasthenia (not genetically caused).
3,4 DAP has been used in a few clinical trials on
patients with CMS.
This drug does not have FDA approval, so it is difficult
for Doctors to perscribe.
3,4 DAP is supposed to work best on presynaptic
defects of the NMJ.
This agent selectively blocks voltage dependent
potassium channels, prolonging
nerve terminal depolarization and thus allows greater
influx of calcium ions at the presynaptic
terminal.Theoretically, this chain of physiological
events results in additional acetylcholine
release. 3,4 DAP has also been used in the treatment
of MS.
Some CMS patients may use a combination of the above therapies to gain maximal benefits.
It should be noted that some therapies and treatments used for
autoimmune myasthenia are
not valid for CMS. Plasmapheresis, thymectomy, and steroid drug therapy
are among these.
Some useful links to myasthenia information
MYASTHENIC SYNDROMES from Washington University - St. Louis
Very
good article on CMS in MDA Quest magazine
If you have any comments or questions please email me at
[email protected]
Best Regards,
Andrew Peake