Susanne Bross Emmerich, Founder and
Executive Director 30 East 72nd St, New York, N.Y. 10021
U.S.A.
Tel: 212 452-1231 Fax: 212 452-1406 E-Mail: ipif@ipif.org
Web Site: http://www.ipif.org
Please
allow me to introduce myself and invite you to join my
newly founded USA IP Support Group based out of upstate
New York.
First, let
me tell you about me and why I had to take on this labor
of love. My name is Anne Ryan and simply stated, I am a
mom. I have a wonderful husband, a beautiful 2-year-old
daughter Willow, and a blessing of another daughter, 9
month old, Kateri. Kateri was born in August, 2002. She
was diagnosed with IP within one week of birth. I can
still feel the fear and hear the words as the doctor read
me pages off the Internet on what incontinentia
pigmenti was. I have never in my life felt so alone.
There was no one to sympathize with the grief my entire
family was feeling and I knew that someday I had to do
something to help.
My
background before being a full time mom was in the
medical field as an Office Manager/Lung Transplant
Coordinator for a pulmonary practice. My husband works
two, yes two, full-time jobs to enable me to be home with
the girls. He is a Youth Division Aide at a Maximum
Secure Facility for Juveniles, and a Personal Fitness
Trainer. We are short on time with one another, short on
money, but rich with love. Our children are our life, and
outside of them, nothing else matters to us. I am also a
professional singer and actress, and hope to be cutting a
demo CD this summer.
(continued
next column)
LETTER
FROM THE EXECUTIVE DIRECTOR
In each of
the previous newsletters I have made an effort to include
articles on subjects that are likely to be among the most
important issues facing people with IP. Presently one of
the most eagerly awaited is the result of the
questionnaire that was sent out on the natural history of
IP. This tried to determine the frequency of specific
symptoms experienced by those with IP. A subject that is
always uppermost in the minds of women with IP who are
contemplating having children, and of women who are
wondering what the consequences will be for the children
of their daughters with IP.
Although
you will read that 700 questionnaires were mailed out,
please keep in mind that many went to families with
several members with IP, and to physicians who have many
patients. The questionnaire is also posted on the web
site and was read and filled out by many more individuals
(exactly how many we have no way of knowing). Therefore
the number 700 really represents many more people. As the
identification of patients was coded, we don't know how
many people actually responded from each of the
categories. The most important fact to keep in mind when
reading the article is that it represents a very small
sampling of patients with IP, and was answered only by
people who have been diagnosed with IP. There is no way
to determine how many have extremely mild symptoms, and
have never been diagnosed but it can safely be assumed
the number is in the thousands. Although the awareness of
IP has been heightened by the identification of the gene,
there are a great many babies born who are misdiagnosed.
This still occurs frequently in many very advanced
medical facilities in major cities around the world.
For the
results to be truly meaningful it is necessary for us to
continue to send out the form, and continue to record the
results for many years to come. I would urge everyone who
did not return the questionnaire to please do so.
As a result
of the identification of the gene causing IP, many women
who have IP now have reproductive options that were
unavailable previously. This newsletter includes articles
describing some of these.
There is
news about support groups as well as other topics of
interest. If you have any suggestions as to what you
would like me to include in subsequent issues, please let
me know.
Susanne Bross Emmerich
THE USA IP
SUPPORT GROUP continued
In January, 2003, I began a website telling of
my story, and creating a forum for families to get in
touch with one another. We have a chatroom, a message
board and a photo gallery. The website is a free one that
I maintain myself, so it is bare bones, but serves the
purpose. My mission is to connect families with other
families via email, snail mail or phone. I ask all
families to "register" with me by filling out a simple
form asking questions about their experience with IP. I
enter them on to a spreadsheet with a brief summary of
their loved one who has IP. This way, when someone asks
to be connected to a similar family situation, I can
easily do so. Most of my announcements etc. will be
posted either on the website or published in the IP
Newsletter, since I will work in conjunction with the IP
International Foundation. My goal is to support, not
advise.
My response
up until this point has been very small simply due to the
lack of exposure to IP families. My hope is that, after
this newsletter, I will receive more interest and be able
to better grow the resources available for the support
group. I utilize as many free services as I can to keep
cost down and avoid any membership dues. This will be a
"one- step-at-a-time" endeavor, and we will make changes
when necessary.
The
concerns of most seem to be geared towards symptoms and
gauging where they are in the realm of them. Some of the
parents I have connected simply email one another to
share stories and struggles, others have picked up the
phone and spoken infrequently.
As of now,
I am one person, and my goal will be to help in any way
that I can. I may not have a glamorous website or vast
resources, but what I do have is heart, compassion, drive
and a belief that one person can make a difference.
Please come
see our website at: http://USAIPSupport.com
or contact me for further information.
Very Truly
Yours,
Anne K.
Ryan
President
USA IP Support Group
748 Central Parkway Schenectady, NY 12309 anne.k.ryan@verizon.net
IP
NATURAL HISTORY STUDY Compiled from Patient
Reports
Ashley
Badgewell, M.S. and
Judith P. Wilner, M.D.
Mount Sinai Medical School
For the
past year, a research project to better document the
natural history (symptoms and clinical course) of IP has
been underway at the Mount Sinai School of Medicine.
Because the types of symptoms and their severity vary
greatly among affected individuals, even within the same
family, the prognosis is difficult to predict. The last
large-scale clinical study of IP was in 1976. As
familiarity with this disorder has increased among
physicians, milder cases of IP have been described. Based
on the cases seen in our practice, we suspected that the
more severe cases might be over-represented in the
literature. We felt a revised natural history of IP was
called for. This is particularly timely since, with the
recent identification of the IP-causing gene DNA-based
testing allows confirmation of diagnosis in milder
cases.
Dr. Judith
Willner, Director of Clinical Genetics at Mt. Sinai, and
I, then a graduate student in Genetic Counseling,
proposed to compile a natural history of IP based on
patient and physician reports. We developed a six-page
questionnaire, consisting of questions regarding
patients’ family histories and medical
histories relevant to IP. It was translated into four
languages. With the assistance of Susanne Emmerich of
IPIF, it was sent to all members of IPIF and posted on
the IPIF website. We had received 152 completed surveys
by March when the initial analysis was performed.
Completed questionnaires have continued to arrive, and we
plan to update the analysis continually. We are very
grateful to all those who participated.
Because the
report on our findings is almost 30 pages long, it is not
possible to reproduce it in its entirety in this
newsletter. Instead, we present a brief summary and
discussion of our most interesting findings. The full
paper will be available on the IPIF website or by
contacting IPIF.
Demographics
of Participants
The
participants were from different backgrounds, as IP is a
condition that affects all races. While the majority of
responses were received from within the United States,
responses were also received from 14 other countries.
Almost half of the participants were Caucasian. Other
ethnic groups represented were Asian, Hispanic, Middle
Eastern and Native American. All but one of our
participants was female. One case of a male affected with
IP surviving to term, but dying after 7 days, was
reported. The age range of the participants in the study
was large. The oldest person represented was 77 years old
at the time of survey completion, and the youngest girl
was 10 months old. There was a fair distribution across
the age groups. 43% of patients surveyed reported at
least one other family member with IP. Questionnaires
were received from multiple members of 18 families.
Although
the average age at diagnosis was calculated as 3.4 years,
the range for age at diagnosis was large. The majority
(68%) were diagnosed by 3 months of age (20% "at birth"),
but some were not diagnosed until childhood (16%
diagnosed between 1-5 years), and, importantly, some were
not diagnosed until adulthood (15%), after they had
affected children, (and, thus skewing the average age of
diagnosis).
64% of
patients were diagnosed on the basis of clinical
findings. 51% had their diagnosis confirmed or originally
made by skin biopsy, and 16% tested positive for the
common NEMO mutation by DNA studies.
Skin
Involvement
Of the
participants, 95% reported having experienced the first
stage of the newborn rash, consisting of small red bumps
and blisters. The average age that the first stage
disappeared was found to be 17 months. The average number
of outbreaks is two. 94% of patients experiencing this
stage reported that the rash was on their arms and legs,
and 54% also reported the initial rash on their stomach,
groin and scalp.
Of the participants, 65% said they
experienced the second stage of the rash, consisting of
dry, rough wart-like sores. The average age of
disappearance is 21 months. For patients who experienced
a recurrent rash, the average number of recurrences is
two, but this number may be misleading as 20% of patients
reported "several" recurrences.
81% experienced this stage on their
arms and legs. Other body parts were also affected, but
in smaller percentages.
Continued page 2, column 1
1
Summer 2003 Page 2
IP
NATURAL HISTORY STUDY
continued
from page 1, column 3
The frequency of the third stage,
consisting of red or grey colored patches of skin, was
found to be 79%, compared with 96%-98% which was
previously reported.Age was taken into
account: 37% of patients, over the age of 10 reported
that this discoloration is still present, and of those
who no longer have discolored areas, the average age of
disappearance was 13.5 years. Recurrences were rare. 79%
experienced these pigmented areas on their arms and legs,
but other areas of the body were also affected.
68% of patients surveyed reported
the fourth stage. In this stage, light colored areas of
skin and hairlessness occur. 49% of the patients over the
age of 10 reported that these light spots are still
present, and of those who no longer have light spots, the
average age of disappearance was 21.5 years. Recurrences
were rare. The majority (81%) experienced light areas on
their extremities. Only 20% of patients reported having a
Wood’s lamp exam to observe subtle
depigmentation.
Scalp/Hair
Symptoms
66% of patients surveyed reported
having bald spots. Of those who reported these hairless
patches, 94% had a bald area at the crown of the head. It
is likely that the hairless spots follow the rash and are
associated with scarring. 38% reported wiry patches of
hair on the scalp.
Nail
Symptoms
51%
reported ridged or otherwise misshapen nails.
Additionally, 9% reported experiencing tumors under their
nails.
Dental
Symptoms
Dental
involvement was reported in 95% of our patients. Of the
patients over the age of 14 years, 29% reported the
continued presence of baby teeth. 56% of patients
reported that their baby teeth were late coming in, and
53% of patients reported their permanent teeth were late
coming in. 60% had baby teeth that never came in and 78%
had permanent teeth that never came in. The average
number of missing baby teeth is four and the average
number of missing permanent teeth is five. About 66% of
patients had baby and/or permanent teeth shaped like pegs
or cones, and 18% had an abnormal amount of decay.
Eye Problems
In order to analyze the ocular findings, it is
necessary to compare the occurrence of eye problems in IP
with that in the general population. In this survey, 12%
of IP patients reported strabismus "cross eyes" or "lazy
eyes"). This is 3 times greater than that observed in the
general population (4%). Bilateral blindness was also
reported in 4% of our patients, almost 6 times greater
than that seen in the general population (0.7%)
Congenital cataracts were seen 30 times more in our
patients (6%) than in the general population (0.2%), and
retinal detachment was seen 27 times more in patients
surveyed (8%) than in the general population (0.3%). For
other eye abnormalities associated with IP such as
problems with the veins of the eye, no general population
risk could be found. Based on our findings, IP patients
are not more likely than the general population to suffer
from astigmatism, myopia, amblyopia or obstructed tear
ducts.
Skeletal Symptoms
Skeletal abnormalities found in previous studies were
thought to be coincidental, not likely to be associated
with IP. In this study, patients were asked to write in
any skeletal problems. Altogether, skeletal anomalies
were reported by 15% of patients. Nine patients (6%)
reported scoliosis (curvature of the spine) but did not
mention if intervention was required. (2% of the general
population suffers from scoliosis.) Four patients (3%)
reported one leg was inches shorter than the other. Other
anomalies including improper hip alignment, and
mandibular anomalies were reported.
Breast
Symptoms
Breast
abnormalities have been associated with IP.Extra nipples were reported in 3.4% of patients.
Four patients reported having one extra nipple, and one
patient reported having two extra. Two patients described
lack of breast growth. Four (2%) patients described
breast asymmetry.
CNS
Involvement
Central
Nervous System disorders present the greatest threat to a
normal life for IP patients. CNS involvement can range
from spastic quadriplegia and mental retardation to
seizures. Altogether, 43 patients, (28%) reported CNS
involvement. This is comparable to the frequency (30%)
suggested by previous studies. However, this number may
be misleading as 85% of patients surveyed have normal
development, with normal mental and motor function.
The
frequency of each CNS disorder is as follows; learning
disabilities were reported by 12.8%, a brain abnormality
detected by CT scan or MRI was reported by 11.2%, newborn
seizures were reported by 9.3%, mental retardation was
reported by 7.6%, an IQ less than 70 was reported by 7%,
cognitive delays were reported by 6.8%, spastic paralysis
was reported by 4.6%, microcephalus (abnormally small
head) was reported by 4.5%, motor delays were reported by
3.8%, hemiparesis (paralysis on one side) was reported by
2.7%, and hearing loss was reported by 1.3%. Some
patients experienced more than one CNS disorder.
It
has been suggested that IP patients who experience
newborn seizures are likely to have a poor prognosis.
However, in this study, only slightly over 50% of
patients who experienced seizures reported another CNS
disorder.
Of the 15
subjects who reported a brain abnormality detected by CT
scan or MRI, 10 (67%) reported experiencing mental/ motor
delays or retardation and 9 of the subjects (60%)
ophthalmologic problems including strabismus, retinal
detachment, cataracts and blindness. Only 2 of the 15
with a radiologically detected brain abnormality did not
have ophthalmologic problems or neurologic impairment.
The average age of diagnosis of a brain abnormality was 6
years. The types of brain abnormalities observed included
abnormal myelination and mild left cerebral hemispheric
atrophy. Larger numbers of patients are needed to
understand the association between brain abnormalities
seen on CT and MRI brain function.
Genetic Test
Results
Chromosome analysis was performed on
21% of patients. All reported normal female chromosomes
(46,XX). Of those who had undergone DNA mutation testing
and knew the result of the test (32% of total surveyed),
84% had tested positive for the common NEMO mutation, and
16% had tested negative for the common mutation. Of the
4% who had participated in linkage studies, linkage was
informative in 63% of patients, and not in the remaining
37%.
Pregnancy
Loss
One or more miscarriages was
experienced by 37% of the IP patients over the age of 20
that we surveyed. This is significantly higher than the
average of recognized miscarriage for the general
population, 3-15%, depending on trimester and maternal
age. The majority of these miscarriages were in the first
trimester and the fetal gender was unknown. While 28% of
fetuses were determined to be male, one (2%) was known to
be female. These data suggest that women with IP are more
likely to miscarry than the general population. Although
for the majority of miscarriages the gender is unknown,
these data confirm the observation that for IP patients,
male fetuses are more likely to result in miscarriages
than female fetuses.
However,
we also inquired about miscarriages experienced by the
mothers of IP patients, whose IP status ranged from
positive to negative to unknown. We found that 47% of IP
patients’ mothers had experienced at
least one miscarriage. As with the IP patients, most of
the miscarriages occurred in the first trimester and the
sex was unknown. Interestingly, the mothers without IP
were as likely to miscarry as the mothers who had IP.
With regard
to family history and pregnancy loss, it was interesting
that 9% of unaffected mothers of daughters with IP
reported multiple miscarriages. 55% percent of the
miscarriages reported were by mothers whose IP status was
unknown or reportedly negative. A third of these women
had more than one daughter with IP. It is possible that
these mothers unknowingly have very mild IP, or they have
a mixture of IP and non-IP cells. Clearly, DNA mutation
testing of mothers of IP girls would resolve this
question and provide more accurate risk assessment for
genetic counseling.
Conclusions
There are
limitations to a patient-reported study, but we were able
to obtain sufficient responses to draw meaningful
conclusions. Our study indicates that more severe cases,
specifically with regard to CNS involvement, have been
previously over-represented in the literature. The large
literature search performed in 1976 suggested that one
out of four children born with IP would have a major CNS
anomaly such as mental and/or motor retardation. Although
almost 30% of the patients in our study reported
experiencing some CNS involvement, only 15
patients (10%) reported serious problems of the central
nervous system such as mental retardation, motor
retardation, and/or chronic epilepsy. Most who
experienced symptoms referable to CNS involvement had
milder problems such as isolated newborn seizures, a
learning disability, or slight speech delay. Although
these problems are not insignificant, the number of
children with IP who will experience grave CNS problems
is closer to one in eight.
We
attempted to determine whether daughters of affected
mothers usually experience more severe symptoms than
their mothers. Unfortunately, although patients reported
experiencing symptoms, the severity was not always given.
Also, it was apparent that severity varied among systems,
i.e. one mother may have had more severe skin
manifestations than a daughter who had severe
neurological complications. The conclusion can be drawn
that a mother’s manifestations will not
necessarily predict their daughter's manifestations.
Almost 40%
of our patients are under the age of 10. We suspect that
physicians have been made more aware of IP in the last 10
years and fewer cases are being missed. Through the
internet, physicians and families have greater access to
medical information and resources. Overall, this results
in a more representative sample of all IP patients who
are being identified earlier and followed
prospectively.
Working
with IPIF, we plan to continue the study. As the data
grow, the frequencies of clinical manifestations will
become better delineated. Earlier diagnosis and knowledge
of the risk for CNS involvement accompanied by widespread
availability of MRI may resolve the question of whether
MRI can aid in prognosis.
Thanks
again to all the patients and their family members who
sent records and photos and took the time to complete our
survey. We are also extremely grateful to Claude
Sansaricq, PhD, MD; Livea Gadea; Adi Bar-Lev, our
translators, Jim Godbold, PhD for assistance with
statistics, and David Nelson, PhD for website
assistance.
2
Summer 2003 Page 3
RESEARCH
UPDATE
There are a
number of women who have been diagnosed with IP who do
not have the common mutation on the NEMO gene.
Several of
these women have had their gene sequenced but their
mutation still could not be identified. There is now an
effort within the research community to try to determine
the exact mutation and which gene is involved. In
subsequent issues of the newsletter progress on this very
important issue will be reported in an effort to keep
everyone up to date on the progress of this project.
PREIMPLANATATION
GENETIC DIAGNOSIS (PGD)
PGD can be performed only on embryos in vitro
(in a laboratory). That means this test is always
performed in conjunction with an in vitro fertilization
cycle.
In
Vitro Fertilization (very brief
summary)
Medication
is given to stimulate the production of multiple
eggs.
* Egg
retrieval is performed using an ultrasound guided
needle.
* Eggs are
then subjected to intracytoplasmic sperm injection
(ICSI), regardless of the quality of the husbands sperm,
to avoid possible genetic contamination by other sperm
sticking to the egg coat. The injected eggs are placed in
the incubator to allow fertilization and embryo growth to
the 6-10 cell stage.
*At this
point, one or two cells will be biopsied from the
embryo(s) and PGD will be performed.
* Normal
embryos are transferred to the mother's uterus on day 4-5
following egg retrieval.
Embryo
Biopsy
To enable
screening of a human embryo before transfer to the
uterus, it is possible to remove one or two cells from
the 6-10 multi-celled embryo without compromising it, so
that the genetic material in these cells can be analyzed.
It must be noted that in routine genetic analysis there
are usually hundreds of cells available for processing,
however, with embryo biopsy only one or two cells are
commonly available, and they must contain a nucleus to
allow determination of the genetic status of that embryo.
The biopsy method is relatively straightforward, but this
does not mean that it is an easy procedure to undertake.
The embryos are typically biopsied at the
pre-implantation stage on day three of development. At
this point, the embryo will be composed of between 4 and
12 cells that are still distinct from each other. On the
third day, however, single cells can be individually
removed without disrupting the adjacent cells in the
embryo. However, at the latest on day 4 the embryo begins
to compact, a process whereby the individual cells lose
their clear outline and become more closely associated
with the each other.
Removing the
Cells
At this time
the embryo is still surrounded by a glygoprotein coat,
the zona pellucida, and to remove any cells this coat
must first be pierced. This can be done either using
acidified culture medium that "dissolves" the zona
pellucida locally, or more conveniently a hole can be
made with a laser, allowing a glass micro-pipette to be
pushed through and extract a cell. The hole that is
drilled is usually made a little smaller than the cell
itself, and this helps to maintain the integrity of the
embryo within its coat during further development in the
IVF lab. During manipulation on an inverted microscope
the embryo is held in a warm culture medium that allows
the cells to be removed with a minimum of trauma to the
overall embryo. The removal of up to a quarter of an
embryo is not known to be deleterious to its further
development, as the embryo can compensate for the loss of
some cells at this early stage of development All cells
at this stage are still totipotent, meaning, that each is
capable of developing into a complete embryo.
Embryo Biopsy
Analysis
Once a single cell (a blastomere) is
removed, it is either fixed on a glass slide for
chromosomal analysis, or placed in a small tube of
chemical buffer for single gene diagnosis. The cells are
then analyzed using techniques called fluorescence in
situ hybridization (FISH) or DNA analysis. During the
genetic analysis, the embryos are usually grown to the
fifth day of development at which time they may either be
at the late morula or blastocyst stage. Those embryos
found to be free of genetic abnormalities are then placed
into the uterine cavity.
Other
Issues
Misdiagnosis
Misdiagnosis can occur due to
mosaicism within the embryo. Some embryos may contain
blastomeres (cells produced by the cleavage
[division] of a fertilized egg) which are
genetically normal and, within the same embryo, other
blastomeres which are abnormal. This is called mosaicism.
For this reason, a diagnosis may be incorrect. This may
result in the transfer of an embryo carrying a chromosome
abnormality or the failure to transfer a normal
embryo.
Experimental error can also account
for a misdiagnosis. Improper cell fixation techniques,
DNA denaturation errors, allelic drop-out or
amplification of contaminated DNA can lead to a wrong
diagnosis.
A recent report of the European
Society of Human Reproduction and Embryology (ESHRE)
documented the PGD results from 25 consortium members
from 1999 to 2001. There were 8 confirmed misdiagnoses
from 451 PGD tested embryos; 1% (3/305) for chromosome
analyses and 3.4% (5/146) for single gene disorders.
Are
there risks associated with PGD?
The
micromanipulation techniques used for blastomere biopsy
are safe with little risk to the embryo. The risk of
accidental damage to the embryo during biopsy is less
than 1%. There is no risk to the embryo following
chromosomal or single gene defect analysis because the
analyzed cells are not put back into the embryo. There
may be a slightly lower likelihood of implantation after
embryo biopsy compared with an embryo not having been
biopsied. Other risks may become apparent over time, but
are far outweighed by the potential benefits for each
couple.
Procedures
In The Embryo Fertilization
Laboratory
Who Takes Care of
the Eggs, Sperm and Embryos in the IVF
Laboratory?
The embryologist is responsible for
the culture, maintenance and protection of the
patients’ eggs, sperm and embryos.
Having received specialized training and meeting
requirements for certification for the reproductive
technology laboratory, the embryologist administers the
laboratory’s operation including the
maintenance and monitoring of the equipment; b) prepares
for and participates in clinical procedures such as egg
retrieval and embryo transfer; c) performs the assisted
reproductive techniques to achieve fertilization and
embryo development; d) documents and records all
laboratory events pertinent to a
patient’s treatment cycle; and e) is an
integral member of the multi-disciplinary treatment
team.
What
is The Sequence of Events in the Laboratory for an IVF
Cycle Involving PGD?
When a
patient initiates a treatment cycle, a specific plan is
developed and established in the IVF Laboratory. Elements
of the plan address the following: the fertilization
procedure, how many eggs are expected; will the patient
wish to freeze extra fertilized embryos
On the day
before egg retrieval, the culture medium is prepared.
Culture vessels which will hold eggs, and the test tubes
in which the sperm are processed are labeled and placed
in the incubator and dedicated workspaces, respectively.
A patient laboratory chart is prepared to confirm her
identity and the semen specimen used for preparation of
the sperm for fertilization of her eggs, to provide a
record of all eggs and embryos and to record the names of
the embryologists and physician and the techniques and
procedures performed by them, confirm the
patient’s identity at embryo transfer,
and to record the culture media used for the patient's
cycle to fulfill quality assurance and control
requirements.
At egg
retrieval, the patient's identity is confirmed, and her
eggs placed in her labeled dishes. The corresponding
semen specimen is accepted after the identification on
the label of the specimen container is confirmed and
recorded in the patient's chart. Motile sperm are
isolated from the semen sample, by a "swim-up" procedure.
According to the treatment plan, after confirmation of
the identities of both eggs and sperm, the eggs are
injected within two to eight hours of retrieval.
After an
incubation period of 15-18 hours, the eggs are examined
to determine if fertilization has occurred. Fertilization
is confirmed when two pronuclei (one each from the sperm
and egg) are observed. In the next 24 hours, the onset of
cell division is confirmed. The egg, with the union of
genetic complements from each parent, will divide into
two cells, and each can divide into two cells. In this
way, the embryo expands in cell number and stage of
development - the egg has become an embryo. On day 3
after egg retrieval, embryos can be selected for
transfer. If there are extra fertilized eggs or embryos,
these can be frozen and stored for potential use in a
future cycle.
The longest
study of children born from in vitro fertilization and
related treatments is reassuring in terms of intelligence
scores and psychological health funded by the European
Union this involved more than 1500 children from Britain,
Belgium, Sweden, Denmark, and Greece tracked up to age 5.
The researchers assessed the physical development and
family relationships and intellectual psychological and
social development.
There were
no differences from the norm in regard to birth weight
and height, nor in intelligence, language skills and
motor skills or in behavior and temperament.
Chorionic
villus sampling
CHORIONIC
VILLUS SAMPLING (CVS)
Chorionic villus sampling (CVS) is a relatively
new procedure used to diagnose certain birth defects in
the first trimester of pregnancy. The test has been
performed regularly since 1982, and many thousand have
been performed around the world. CVS is a prenatal test
that involves taking a tiny tissue sample from outside
the sac where the fetus develops. This tissue contains
the same genetic material as the fetus.
(Continued
page 4, column 1)
3
Spring 2002 Page 4
CHORIONIC
VILLUS SAMPLING (CVS)
(Continued from page 3, column 3)
The chorion
is the portion of fetal membrane that eventually forms
the fetal side of the placenta. The chorion contains
villi which are small finger-like projections. These
villi are snipped or suctioned off for study in the
procedure. The chorionic villi are of fetal origin so
examining the samples of them can give the genetic makeup
of the fetus. This test is performed as an early
detection tool of congenital defects.
The test
generally is performed between 10 and 12 weeks after a
woman’s last menstrual period. CVS
usually is not recommended if a woman has bleeding or
spotting during the pregnancy.
How
is CVS Performed?
CVS
requires taking a small piece of the chorionic villi,
which are wisps of tissue that attach the pregnancy sac
to the wall of the uterus. A laboratory analyzes cells
from the villi, which normally have the same genetic and
biochemical makeup as the fetus. Test results are
generally available in about 10 days, although
preliminary results may be available sooner.
How
is the Sample Taken?
First, the
vagina and cervix are thoroughly cleansed with an
antiseptic. Then, using ultrasound as a guide, a
physician inserts a thin tube through the vagina and
cervix (transcervical CVS) to the villi, and uses gentle
suction to remove a small sample. No anesthetic is
required. Some women say CVS doesn't hurt at all; others
experience cramping or a pinch when the sample is
taken.
Depending
upon an individual woman’s anatomy, the
physician may choose to reach the chorionic villi by
inserting a needle through the abdominal wall
(transabdominal CVS), also using ultrasound guidance.
Studies have found the two forms of CVS to be equally
safe, unless the woman has a retroverted (tipped) uterus,
in which case the risk of miscarriage is higher if the
procedure is done transcervically. Therefore,
transabdominal CVS is recommended for women with a
retroverted uterus. If the location of the placenta
prevents this procedure, amniocentesis can be considered
as an alternative.
After the
sample is taken, the fetus’s heartbeat
is checked with ultrasound before the woman leaves the
examination room. Most physicians recommend that a woman
take it easy for several hours after CVS. One in five
women experience cramping following CVS; 1 in 3 women
have some bleeding or spotting, which ordinarily stops
within a few days. A woman always should report these
symptoms to her health care provider.
Is
CVS Safe?
More than
200,000 women worldwide have undergone CVS, which was
introduced in this country in 1983. Studies suggest that
CVS may be slightly more likely than amniocentesis to
cause miscarriage. According to the Centers for Disease
Control and Prevention, between 1 in 200 and 1 in 100
women miscarry after CVS. That risk rises to about 5 in
100 for a woman with a retroverted uterus who has
transcervical CVS. The risk of pregnancy loss following
CVS is lower when the physician performing the procedure
is highly experienced and when the testing facility
provides both transcervical and transabdominal CVS
(allowing the safer option for each patient). Recent
studies suggest that the rate of miscarriage following
CVS and amniocentesis (at 15 to 18 weeks) may be about
the same with experienced doctors in such facilities.
CVS test
results are very accurate (greater than 99 percent) in
ruling out certain chromosomal birth defects and specific
genetic problems.
ECTODERMAL
DYSPLASIA SOCIETY IS IP SUPPORT GROUP IN
U.K.
The IP
support group that was started in England by Nicola
Blasdale and Claire Britton has been discontinued. Nicola
moved to New Zealand and it was difficult for one person
to handle it alone. The IP newsletter #7 of Spring 2002
explained the fact that IP is one of several Ectodermal
Dysplasia disorders. Several months ago an offer was made
to the Incontinentia Pigmenti International Foundation by
the Ectodermal Dysplasia Society (EDS) in England to
include those with IP into its membership.This seemed
like a wonderful idea especially since they already have
several members with IP. It is run by Mrs. Diana Perry,
108 Charlton Lane, Cheltenham, Gloucester, GL53 9EA
England. Tel: 242 261-332;
The EDS
publish a newsletter called EDlines, and in the July 2002
issue gave a thorough explanation of IP, by Dr. Helen
Stewart of Churchill Hospital, Oxford.
On April
14th EDS held their first conference at
Hothorpe Hall, Leicestershire. It was attended by about
80 adults and 35 children, as well as the members of
their Medical Advisory Board. The conference began with
an introduction and history of ED followed by a second
presentation by a pediatric dentist. More presentations
were made followed by lunch. Then an open forum was held
at which all the members of the Medical Advisory Board
gave answers to questions raised within the field of
their work. Children were cared for all day and were
involved in craft activities based on an Easter theme,
sport, team games, etc. for all ages. I would like to
encourage all those in the U.K. to take advantage of this
relationship and to join the ED Society.
TIPS
FOR HEALTHY NAILS
Keeping
your nails strong is largely about limiting their
exposure to water and chemicals. The following steps will
help you fend off problems:
1. Wear
gloves during household chores especially when cleaning
with solvents.
2. Use
moisturizing lotion on your nails as well as hands after
exposure to water and before bed.
3. Don't expect
calcium, gelatin, vitamins, or other supplements to help.
Nothing you ingest can directly improve the condition of
your nails.
4. File in one
direction only, not back and forth, which can cause
splits. Don't pick at hangnails; clip them close to the
skin and leave them alone.
5. Choose polish
removers with acetate, rather than acetone, which can dry
nails. Use as rarely as possible.
6. If you get
manicures or pedicures, make sure instruments are
sterile. If you're skeptical of your shop's methods,
bring your own manicure set along with you.
7. Avoid having
your cuticles cut or pushed back; that ups the risk of
infection.
8. If you have
characteristically thin nails, consider using a drugstore
nail-strengthening product or nail polish to help harden
them.
9. Clip
toenails, regularly, cutting straight across, to prevent
ingrowth. Avoid tight-fitting shoes, which can cause
abnormal nail curvature, ingrowth, and other
problems.
TIPS
FOR MAINTAINING HEALTHY HAIR AND
SKIN
One of the
skin derivatives that can be affected by IP is hair.
However, maintaining healthy hair is a good idea for
everyone, and after some research I've come up with the
following advice.
Many basic
hair-maintenance steps, such as shampooing, combing, and
brushing, can actually cause hair to become too brittle
and break when done too frequently. To minimize damage,
shampoo only often enough to keep hair fresh and clean,
and use a cream rinse or conditioner to make it more
manageable and easier to comb. Avoid vigorous towel
drying; wet hair is more fragile and thus more prone to
breakage. And instead of the old "100 brush strokes a
day" rule, use a wide-toothed comb, or brush sparingly
with a brush that doesn't snag.
Length and
style can also have a bearing on hair health. Long hair
is particularly susceptible to damage since
it’s more likely to become tangled and
has been exposed to the elements longer. And tightly
pulled styles, such as ponytails or braids, can cause
hair to bread or fall out, particularly along the sides
of the scalp.
While
chemical treatments such as relaxants, permanent waves,
and coloring are generally safe in moderation, they can
cause significant damage to the hair shaft if done
incorrectly or excessively. Heat styling poses similar
risks, especially with the intense, direct heat of the
curling or flattening irons. To prevent
“overprocessed”
hair, avoid leaving solutions on too long, having two
chemical procedures done on the same day, or bleaching
hair that's already bleached. If your hair starts to seem
"fried" or "brittle", or you're losing a
higher-than-normal amount of hair (more than 50 to 100
strands per day), reduce heat and chemical processing to
a minimum and let the hair grow out for a while.
Unfortunately,
fried-looking hair isn't the greatest risk posed by
relaxants, dyes, and other hair chemicals. Look for "no
lye" relaxants, which may irritate the scalp less than
"lye" formulas. With dyes, do a patch test to make sure
the product doesn’t cause irritation or
an allergic reaction: Apply a dab behind your ear and/or
inside your elbow and leave it there for two days,
watching for itching, redness, burning, or other
reactions. Finally, although do-it-yourself products may
be more economical, consider having your hair relaxed or
colored by a professional who's familiar with the various
brands and formulas.
Hairpiece,
wigs, and weaves offer still another option, without any
of the potential risks of drugs or going under the
knife.
TANNING
THE SAFE WAY
As IP is a
disorder that affects the skin and skin derivatives, it
is important to care for ones skin properly. Many people,
even those without IP, should be very careful in the sun.
With skin cancer rates on the rise, more people have
gotten the message to avoid the sun. Don't trust the
shade. Just because you're sitting under a leafy tree
doesn't mean you're safe from the sun. For example, if
half the sky is visible through the canopy, the tree
shields you only as much as a sunblock with a SPF of 2.
So unless the canopy is nearly impenetrable, you'll
generally still need to apply sunscreen.
Looking for
another way to get that perfect tan, a growing number are
turning to sunless tanning products, including oils,
sprays and lotions as well as salon treatments that don't
involve heat or light. But not all sunless tanners are
effective, and a few can even be harmful.
Doing a
little homework can keep you from getting burned.Tanning
pills often contain an ingredient called canthaxanthin,
which in small amounts is approved by the Food and Drug
Administration as a color additive in food. The much
larger doses found in pills can create the appearance of
a tan by making the skin turn a color ranging from orange
to brown, depending on the individual. This use, which
isn't FDA approved, can cause side effects, including
stomach upset, severe itching, welts and temporary vision
damage.
(Continuted
Page 5, Colunm 1)
4
Summer 2003 Page 5
TANNING
THE SAFE WAY
(Continuted
from Page 4, Colunm 3
Other
brands of pills contain beta carotene or lycopene, which
are cousins of canthaxanthin. Still others have tyrosine,
an amino acid that’s promoted as a way
to boost the production of melanin, the pigment that
gives skin its color. Dermatologists say none of these
ingredients have been adequately tested as tanners for
safety and effectiveness, and pills containing them
should be avoided.
The only
FDA-approved ingredient, DHA, is found in most topical
tanning products, including sprays, lotions, mousses,
gels, foam and towelettes. It works by reacting with
proteins in the dead outer layer of skin and producing a
dark color that resembles a tan. As the skin naturally
sloughs off, the color fades and disappears after five to
seven days. Though DHA is considered safe, some people
have allergic skin reactions to certain products. That's
why it's a good idea to first test a sunless tanner on a
small patch of skin. For best results, it's also
important to shave and exfoliate your skin before
applying the product. Generally, it takes several hours
for DHA to start to work; though some products also have
"bronzers" cosmetics that provide instant color.
More
expensive tanners don’t necessarily
work better. Some brands make certain people's skin look
orange instead of brown, while others are hard to apply
evenly to all parts of the body. To avoid these problems,
you can go to a salon where they apply DHA containing
tanning solutions for you. In some cases, that entails
lying on a table and having someone rub in the tanner. In
others, it requires stepping into a booth, where nozzles
spray a mist over your entire body, much like at a car
wash.
Unlike a
real tan, which provides a small amount of protection
from sunburn, a tan from a bottle or salon won't protect
your skin. Some products add sunscreen, but it loses its
effectiveness within hours, long before your tan fades.
That's why you still need sunscreen but don't worry: it
won't interfere with a fake tan.
The
information provided in our newsletter should not be
substituted for personal, professional advice. It is our
intention to keep you informed and ask you to always
check any treatment with your
physician.
Dr.
HARVEY PAUL SINGER
(Director
of Pediatric Neurology, The Johns Hopkins Hospital;
Professor of Neurology and Pediatrics, The Johns Hopkins
University School of Medicine; Member of the Scientific
Advisory Council, Incontinentia Pigmenti International
Foundation)
Walter H.
Stern
When you hear someone say: "My work is my hobby," you
know you're on the trail of a success story. And so it is
with Dr. Harvey Saul Singer who admits to few hobbies but
professes a deep attachment to clinical research in
neurology. So deep, in fact, that he has devoted more
than thirty years of his life to pursuing the causes of,
and hopefully answers to, a broad spectrum of
neurological disorders at Johns Hopkins University School
of Medicine in Baltimore. Dr. Singer made an early
decision to forgo private practice in favor of an
academic foray into a highly specialized field and, as he
is quick to point out, all in one place. It came soon
after his medical studies at Western Reserve University
School of Medicine in Cleveland when he embarked on
laboratory work. His lab experience made it clear that he
needed to contribute to knowledge of certain "storage
diseases," disorders that result from genetic
malfunctions. Tourette Syndrome provided his first focus
in a widely diversified field.
He had
ample time to confirm his decision. During the Vietnam
war, by virtue of the so-called Berry plan, he was
permitted to finish his medical studies with the proviso
that he join the armed forces immediately thereafter. It
landed him on the staff of the Ireland Army Hospital in
Fort Knox, Kentucky, where, between duty assignments he
could contemplate his future. This and his laboratory
experience cast the die.
In the
course of his career, he served as both assistant and
associate professor at the Johns Hopkins Department of
Neurology as well as the same titles in the Department of
Pediatrics. It was the former, however, that captured his
imagination in that both disciplines are eventually fused
into a combined field of research. He is now chief of
pediatric neurology.
It was not
until 1990 that Dr. Singer encountered his first
diagnosed case of incontinentia pigmenti Along
with much of the medical fraternity he was baffled by it.
A mutant case of herpes, most physicians thought at that
time. But they eventually learned better. Dr. Singer and
two associates published a paper on IP, one of many
studies published by him on a variety of subjects.
The IP
study caught the attention of the Incontinentia Pigmenti
International Foundation and he was asked to join its
Scientific Advisory Council, one of numerous boards and
directorships Dr. Singer holds. His advice to the
Foundation has been invaluable and will continue to be
now that the gene has been identified.
Rarely seen
on a golf course, Dr. Singer prefers hiking and biking
with his wife Debbie, a former teacher and now a docent
at the Baltimore Museum of Art. Of their two sons, 35 and
33, the elder is studying physical therapy and the
younger is a lawyer.
NEED
FOR CONTRIBUTIONS AND FUNDING
IPIF
is grateful to its supporters for their ongoing
generosity. IPIF is completely run by volunteers,
therefore there are no administrative expenses. IPIF
needs your contributions now to continue its valuable
work, the services it provides, as well as funding the
expenses of the International IP Research Consortium.
Raising
funds for a rare disorder is extremely difficult.
Most public foundations wish only to fund the larger,
better-known health organizations, usually those which
are receiving the most publicity.
As
ground-breaking as the identification of the gene NEMO
that causes IP was, there were no newspapers in the U.S.
willing to carry the story. Even government agencies have
refused financial support. Therefore, it is up to the
families, friends and relatives of those with IP to
help.
If
you have not become a member, or have not renewed your
membership please consider doing so.
Several
individuals have taken the opportunity to make a gift in
honor of a deceased friend or loved one, or sent in a
contribution to celebrate a special occasion such as a
birthday, anniversary, graduation, etc. When such a
contribution is made a letter is sent, to the family
being so honored, acknowledging the contribution.
One
may also consider giving a fund-raising event such a tea
party, cocktail party, auction, etc.
Please keep in mind that whatever the reason, your
contribution is essential.
Chorionic
villus sampling