This Page is intended for Health Professionals.
Please keep checking back for updates on this
page.
On
the foundation registry we have over
875
documented
confirmed case all over the world.
MRI
Exam if cerebral stroke is suspected.
CADASIL is a rare genetic condition that results
from a mutation on the Notch 3 gene in chromosome 19.
Must
Avoid
Thrombolyisis
& anticoagulant treatments, Arteriography, Vasoconstricting medicines (issued from rye
ergot or from Tripoptan) and products aimed at unblocking blood vessels as they increase
the risk of a hemorrhage.
Clinical - Onset
Adult-hood, Recurrent Sub-cortical Ischemic
Events, Strokes, Migraine like headaches, Cognitive Dysfunction: Dementia; Psychiatric
disorders & Neuropathy.
SHOULD
A CADASIL PATIENT TAKE ASPIRIN? Yes,
There is no scientific evidence that aspirin plays a preventive role in CADASIL, however,
based on what is currently known in stroke patients, we usually recommend this treatment
if there is non contra-indication and the occurrence of a first ischemic event. The tough
decision is deciding what to do when patients have TIA’s and strokes despite
treatment with aspirin. Because of the risk of hemorrhage and lack of evidence, blood
thinners such as warfarin and clot busters like TPA are not recommended.
HOW
MUCH ASPIRIN SHOULD BE TAKEN? The
dose of aspirin most currently evaluated in therapeutic trials is between 75 mg to 325mg. Asymptomatic CADASIL patient should have a
low dosage of aspirin and a patient with a history of TIA’s or stroke could be given
a higher dose of aspirin per day. It is recommended to take coated aspirin.
50%
OF HEREDITARY
CADASIL
is passed as a dominant mutation and offspring have a 50% chance of developing the
disease. All mutation carriers develop some form of the illness (complete penetrance)
though the timing and severity and symptoms may vary in family members with the same
mutation. Women with CADASIL live longer than men on average. So there are other genetic
and environmental factors, yet to be identified, that modulate gene expression. A de
novo mutations (A de novo mutation is a new mutation) can rarely occur in exceptional
isolated cases without a prior family mutation.
We
have the dilemma of whether our CADASIL offspring should or should not be tested
for CADASIL. The below article "Russian
Roulette - The Experience of Being "At Risk" for Huntington's disease. Huntington’s Disease is a 50% change of an
inheriting disease like CADASIL. Russian
Roulette Article
CADASIL
Tissue Bank -
Why is brain donation important? A
brain autopsy is the only way to confirm the cause of dementia. Researchers rely on
information from autopsies of donated brains to learn how CADASIL and other dementias
affect the brain. By understanding these diseases better, researchers hope to develop
better treatments and cures for them.http://www.memorydisorder.org/braindonation.htm
PRESENTATIONS
AND REPORTS
May 2007 - Marie Germaine Bousser from France Presented at Shreveport
LA
July 2006 Presentation by New York University School of Medicine. A
personal thank you to the entire health professionals who work with CADASIL. Please click
on this paragraph to view this presentation.
2006 - Click here to view a case study put together following the
first time admission of a patient with CADASIL. The case study formed part of an
assessment for a post-graduate paper in nursing
2005 Presentation Gregory Pastores at ULF conference
MRI Reports
Blood Tests Results
Skin Biopsy Report
To review an Autopsy Report of a 66 year old person with CADASIL.
Click anywhere on this sentence to view in a pdf form.
Blood
Test results from Testing Labs -
Date
of report 08-06
DNA
variant 1: Transition G > A
Nucleotide
Position: 776
Codon
Position: 233
Amino
acid change: Cysteine > Tyrosine
Variant
Type: Predicted
disease associated mutation.
Date
of report 08-06
DNA
variant 2: Transition G > A
Nucleotide
position: 1803
Codon
position: 575
Amino
acid position: None
Variant
type: Unknown
polymorphism.
Date
of report 3-16-2006
DNA
variant 1: Transition G > A
Nucleotide
position: 743
Codon
position: 222
Amino
acide change: Cysteine > Tyrosine
Variant
type: Disease-associated mutation
Date
of report 11-8-05
DNA
variant 1: Transition C > T
Nucleotide
position: 499
Codon
position: 141
Amino
acide change: Arginine > Cysteine
Variant
type: Disease-associated mutation
(R141C)
Date
of this report 10-8-01
C
to T base change at position 622
in
exaon 4 of the Notch 3 gene resulting
in
the subsitution of a cysteine (TGC)
for
an arginine (CGS) at positon 182. (R182C)
Date
of report 7-6-01
Heterozygous
for a C or T base change at
nucleotide
505 of the Notch 3 gene that
changes
a condon for arginine (CGS)
to
one for cysteinine (TGC) at
amino
acide position 169. (R169C)
THE ROLE OF NOTCH3 IN STROKE
Investigators: N. Carolyn Schanen,
MD, PhD
Background: CADASIL is an inherited vascular dementia characterized by migraine with aura,
severe mood disturbances, recurrent ischemic strokes, and dementia. In 1996, CADASIL was
shown to be caused by mutations in the NOTCH3 gene. NOTCH3, located on chromosome 19, is
part of a gene family that encodes a large transmembrane receptor that is crucial for cell
fate determination during embryonic development. Notch3 receptors consist of an
extracellular domain involved in ligand binding and an intracellular domain involved in
signal transduction, with all known CADASIL mutations residing in the extracellular domain
of the Notch3 receptor.
Utilizing
five independent mutations analogous to those found in CADASIL patients, we studied the
effects of these mutations on protein processing and cell surface expression. Both the
unprocessed full-length form and the processed heterodimeric form were observed on the
cell surface, suggesting that the Notch3 CADASIL mutations do not affect protein
expression, processing, or cell surface localization. Given that the mutations all occur
within the extracellular, ligand-binding domain of Notch3, we also evaluated whether
ligand binding to a soluble form of the Delta1 ligand would be compromised with our
CADASIL mutants. Delta1-Notch3 binding was detected for all five Notch3 CADASIL mutant
proteins. Thus, these mutations do not inhibit receptor-ligand interactions. For more
information, go to www.americanheart.org,
N. Carolyn Schanen, MD, PhD, Head, Human
Genetics Research Lab, Adjunct Assistant Professor in Human Genetics, UCLA School of
Medicine
If you would like to add to this page or have any questions or suggestions, please
e-mail us at info@cadasilfoundation.org
