The majority ofpersons with XX male syndrome have the Y chromo-some gene SRY attached to one of their X chromosomes.The rest of the individuals with XX male syndrome donot have SRY detec
Trang 1The prognosis for patients with L1CAM mutations is
highly variable The most severe cases of L1CAM
muta-tions involve fetal demise, presumably because of the
pressure exerted on the developing brain by the
hydro-cephaly However, in less severe cases, the lifespan is
determined primarily by general health and care factors
A number of patients with less severe L1CAM spectrum
disorders have lived at least into their 50s
Resources
PERIODICALS
Fransen, E., et al “L1-associated Diseases: Clinical Geneticists
Divide, Molecular Geneticists Unite.” Human Molecular
Genetics 6 (1997): 1625–1632.
Kenwrick, S., M Jouet, and D Donnai “X Linked
Hydrocephalus and MASA Syndrome.” Journal of
Medical Genetics 33 (1996): 59–65.
Kenwrick, S., A Watkins, and E De Angelis “Neural Cell
Recognition Moleculae L1: Relating Biological
Complexity to Human Disease Mutations.” Human
National Institute of Neurological Disorders and Stroke 31
Center Drive, MSC 2540, Bldg 31, Room 8806, Bethesda,
indi-mosomes Two types of XX male syndrome can occur:
those with detectable SRY gene and those withoutdetectable SRY (Sex determining region Y) SRY is themain genetic switch for determining that a developingembryo will become male
Description
XX male syndrome is a condition in which the sexchromosomes of an individual do not agree with thephysical sex of the affected person Normally there are
46 chromosomes, or 23 pairs of chromosomes, in eachcell The first 22 pairs are the same in men and women.The last pair, the sex chromosomes, is two X chromo-somes in females (XX) and an X and a Y chromosome inmales (XY)
In XX male syndrome, the person has female mosomes but male physical features The majority ofpersons with XX male syndrome have the Y chromo-some gene SRY attached to one of their X chromosomes.The rest of the individuals with XX male syndrome donot have SRY detectable in their cells Hence, othergenes on other chromosomes in the pathway for deter-mining sex must be responsible for their male physicalfeatures
chro-Genetic profile
In XX male syndrome caused by the gene SRY, atranslocation between the X chromosome and Y chromo-some causes the condition A translocation occurs whenpart of one chromosome breaks off and switches placeswith part of another chromosome In XX male syndrome,the tip of the Y chromosome that includes SRY is translo-cated to the X chromosome As a result, an embryo with
XX chromosomes with a translocated SRY gene willdevelop the physical characteristics of a male Typically,
a piece of the Y chromosome in the pseudoautosomalregion exchanges with the tip of the X chromosome In
XX male syndrome, this crossover includes the SRY tion of the Y
por-In individuals with XX male syndrome who do nothave an SRY gene detectable in their cells, the cause ofthe condition is not known Scientists believe that one ormore genes that are involved in the development of the
Trang 2son These genes could be located on the X chromosome
or on one of the 22 pairs of autosomes that males and
females have in common As of 2001, no genes have been
found to explain the female to male sex reversal in
peo-ple affected with XX male syndrome who are SRY
neg-ative Approximately 20% of XX males do not have a
known cause and are SRY negative It is thought that
SRY is a switch point, and the protein that is made by
SRY regulates the activity of one or more genes (likely
on an autosomal chromosome) that contribute to sex
development Also there have been some studies that
demonstrate autosomal recessive and autosomal
domi-nant inheritance for the XX male
Demographics
XX male syndrome occurs in approximately one in
20,000 to one in 25,000 individuals The vast majority,
about 90%, has SRY detectable in their cells The
remaining 10% are SRY negative, although some
research indicates that up to 20% can be SRY negative
XX male syndrome can occur in any ethnic background
and usually occurs as a sporadic event, not inherited from
the person’s mother of father However, some exceptions
of more than one affected family member have been
reported
Signs and symptoms
SRY positive XX male syndrome
Males with SRY positive XX male syndrome look
like and identify as males They have normal male
phys-ical features including normal male body, genitals, and
testicles All males with XX male syndrome are infertile
(cannot have biological children) because they lack the
other genes on the Y chromosome involved in making
sperm Men with XX male syndrome are usually shorter
than an average male, again because they do not have
cer-tain genes on the Y chromosome involved in height A
similar syndrome that effects males with two X
chromo-somes is Klinefelter syndrome Those individuals with
46XX present with a condition similar to Klinefelter,
some female structures such as the uterus and fallopiantubes Men with SRY negative XX male syndrome canalso have gynecomastia, or breast development duringpuberty, and puberty can be delayed As with SRY posi-tive XX male syndrome, these men are infertile andshorter than average because they lack other Y specificgenes The physical features can vary within a family, butmost affected people are raised as males
A small portion of people with SRY negative XXmale syndrome are true hermaphrodites This means theyhave both testicular and ovarian tissue in their gonads.They are usually born with ambiguous genitalia, wherethe genitals of the baby have both male and female char-acteristics Individuals with XX male syndrome and truehermaphrodites can occur in the same family, suggestingthere is a common genetic cause to both Research indi-
K E Y T E R M SAutosomes—Chromosome not involved in speci-
fying sex
Chromosome—A microscopic thread-like
struc-ture found within each cell of the body and sists of a complex of proteins and DNA Humanshave 46 chromosomes arranged into 23 pairs.Changes in either the total number of chromo-somes or their shape and size (structure) may lead
con-to physical or mental abnormalities
Embryo—The earliest stage of development of a
human infant, usually used to refer to the first eight
weeks of pregnancy The term fetus is used from
roughly the third month of pregnancy until ery
deliv-Gene—A building block of inheritance, which
contains the instructions for the production of aparticular protein, and is made up of a molecularsequence found on a section of DNA Each gene isfound on a precise location on a chromosome
Trang 3XX male syndrome until they try to have their own
chil-dren, are unable to do so, and therefore are evaluated for
infertility
When the condition is suspected in a male,
chromo-some studies can be done on a small sample of tissue
such as blood or skin The results show normal sex
chro-mosomes, or XX chromosomes Further genetic testing
is available and needed to determine if the SRY gene is
present
Some affected individuals have had SRY found in
testicular tissue, but not in their blood cells This is called
mosaicism Most males have only their blood cells tested
for SRY and not their testicular tissue Hence, some men
who think they have SRY negative XX male syndrome
may actually be mosaic and have SRY in their gonads
XX male syndrome can be detected before a baby is
born This occurs when a mother-to-be has prenatal
test-ing done that shows female chromosomes but on
ultra-sound male genitals are found Often the mother has had
prenatal testing for a reason other than XX male
syn-for the presence of the SRY gene can be done by an
amniocentesis An amniocentesis is a procedure in
which a needle is inserted through the mother’s abdomeninto the sac of fluid surrounding the baby Some of thefluid is removed and used to test for the presence of theSRY gene Amniocentesis slightly increases the risk ofmiscarriage
Treatment and management
For those with XX male syndrome with normal malegenitals and testicles, no treatment is necessary Affectedmales with hypospadias or undescended testicles mayrequire one or more surgeries to correct the condition Ifgynecomastia is severe enough, breast reduction surgery
is possible The rare person with true hermaphrodismusually requires surgery to remove the gonads, as theycan become cancerous
Parents who learn their child has been diagnosedwith XX male syndrome are encouraged to gain bothemotional and educational support Issues such as
Disorders associated with multiple X or Y chromosome inheritance
Disorder Chromosome affected Karotype Incidence Symptoms
Turner syndrome X 45,X (monosomy) 1 in 2,000 Growth retardation
Infertility Cardiovascular malformations Learning disabilities Klinefelter syndrome X 47,XXY (trisomy) 1 in 500–800 Taller than average
Poor upper body strength;
clumsiness Mild intentional tremor (20–50%) Breast enlargement (33%) Decreased testosterone production Infertility
Dyslexia (50%) Triple X X 47,XXX (trisomy) 1 in 1,000 Mild delays in motor, linguistic and
emotional development Learning disabilities Slightly taller than average XYY syndrome Y 47,XYY 1 in 1,000 Taller than average
Lack of coordination Acne
Some infertility Learning disabilities (50%) Behavior problems, especially impulse control
XX male syndrome Y 46,X,t(X,Y) (translocation 1 in 20,000–25,000 Usually normal male physical
features but may have ambiguous genitalia, hypospadias or undescended testes Infertility
Shorter than average
of the SRY gene [90%]
or other gene responsible for male sex determination)
Trang 4of both medical professionals, and those whose own
chil-dren live with the condition
Prognosis
The prognosis for males with XX male syndrome is
excellent Surgery can usually correct any physical
prob-lems Men with XX male syndrome have normal
intelli-gence and a normal life span However, all affected men
will be infertile
Resources
BOOKS
Wilson, J.D., and J.E Griffin “Disorders of Sexual
Differentiation.” In Harrison’s Online Edited by Eugene
Braunwald, et al New York: McGraw-Hill, 2001.
PERIODICALS
Abramsky, L., et al “What Parents Are Told After Prenatal
Diagnosis of a Sex Chromosome Abnormality: Interview
and Questionnaire Study.” British Medical Journal 322
(2001): 463–466.
Biesecker, B “Prenatal Diagnoses of Sex Chromosome
Conditions: Parents Need More Than Just Accurate
Information.” British Medical Journal 322 (2001): 441–2.
Zenteno, Juan, et al “Two SRY-negative XX Male Brothers
Without Genital Ambiguity.” Human Genetics 100 (1997):
XYY syndrome is a chromosome disorder that
tal institutes Based on these observations, men withXYY syndrome were labeled as overly aggressive andlikely to be criminals
These original observations did not consider that themajority of males with XYY syndrome were not in pris-ons or mental institutes Since then, broader, less biasedstudies have been done on males with XYY syndrome.Though males with XYY syndrome may be taller thanaverage and have an increased risk for learning difficul-ties, especially in reading and speech, they are not overlyaggressive Unfortunately, some text books and many
people still believe the inaccurate stereotype of the male syndrome.
super-Genetic profile Chromosomes are structures in the cells that con-
tain genes Genes are responsible for instructing our ies how to grow and develop Usually, an individual has
bod-46 chromosomes in his or her cells, or 23 pairs The first
22 pairs are the same in males and females and the lastpair, the sex chromosomes, consist of two X chromo-somes in a female, and an X chromosome and an Y chro-mosome in a male
XYY syndrome occurs when an extra Y some is present in the cells of an affected individual.People with XYY syndrome are always male The errorthat causes the extra Y chromosome can occur in the fer-tilizing sperm or in the developing embryo
chromo-XYY is not considered an inherited condition Aninherited condition usually is one in which the motherand/or father has an alteration in a gene or chromosomethat can be passed onto their children Typically, in aninherited condition, there is an increased chance that thecondition will reoccur The risk of the condition reoccur-ring in another pregnancy is not increased above the gen-eral population incidence
Trang 5age) Many males with XYY syndrome are not overly
muscular, particularly in the chest and shoulders
Individuals with XYY syndrome often have difficulties
with their coordination As a result, they can appear to be
awkward or clumsy During their teenage years, males
with XYY syndrome may develop severe acne that may
need to be treated by a dermatologist
Men with XYY syndrome have normal, heterosexual
function and most are fertile However, numerous case
production However, a minority of males with XYYsyndrome may have increased amounts of some hor-mones involved in sperm production This may result ininfertility due to inadequate sperm production As of
2001, the true incidence of infertility in males with XYYsyndrome is unknown
When XYY men make sperm, the extra Y some is thought to be lost resulting in a normal number
chromo-of sex chromosomes As a result, men with XYY drome are not at an increased risk for fathering childrenwith chromosome abnormalities However, some menwith XYY syndrome have been found to have moresperm with extra chromosomes than what is found inmen without XYY syndrome Whether these men have
syn-an increased risk of fathering a child with a chromosomeabnormality is unknown as of 2001
Men with XYY syndrome usually have normal ligence, but it can be slightly lower than their brothersand sisters Approximately 50% of males with XYY syn-drome have learning difficulties, usually in language andreading Speech delay can be noticed in early schoolyears Males with XYY syndrome may not process infor-mation as quickly as their peers and may need additionaltime for learning
intel-Males with XYY syndrome have an increased risk ofbehavior problems Hyperactivity and temper tantrumscan occur more frequently than expected, especially dur-ing childhood As males with XYY syndrome becomeolder, they may have problems with impulse control andappear emotionally immature
From a psychosocial standpoint, males with XYYsyndrome may have low self-esteem due to mild learningdisabilities and/or lack of athletic skills due to lack ofcoordination Males with XYY syndrome are at risk instressful environments and have a low ability to deal withfrustration
As of 2001, men with XYY syndrome are notthought to be excessively aggressive or psychotic.However, because some men with XYY syndrome canhave mild learning difficulties and/or have difficulty con-trolling behavior problems such as lack of impulse con-trol, their actions may lead to criminal behavior if placed
in the right environment It is important to emphasize thatthis occurs only in a small percentage of men with XYYsyndrome Most men with XYY syndrome are produc-tive members of society with no criminal behavior
Diagnosis
K E Y T E R M SAmniocentesis—A procedure performed at 16–18
weeks of pregnancy in which a needle is inserted
through a woman’s abdomen into her uterus to
draw out a small sample of the amniotic fluid from
around the baby Either the fluid itself or cells from
the fluid can be used for a variety of tests to obtain
information about genetic disorders and other
medical conditions in the fetus
Cell—The smallest living units of the body which
group together to form tissues and help the body
perform specific functions
Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10–12 weeks
gesta-tion Under ultrasound guidance a needle is
inserted either through the mother’s vagina or
abdominal wall and a sample of cells is collected
from around the fetus These cells are then tested
for chromosome abnormalities or other genetic
diseases
Chromosome—A microscopic thread-like
struc-ture found within each cell of the body and
con-sists of a complex of proteins and DNA Humans
have 46 chromosomes arranged into 23 pairs
Changes in either the total number of
chromo-somes or their shape and size (structure) may lead
to physical or mental abnormalities
Embryo—The earliest stage of development of a
human infant, usually used to refer to the first eight
weeks of pregnancy The term fetus is used from
roughly the third month of pregnancy until
deliv-ery
Hormone—A chemical messenger produced by
the body that is involved in regulating specific
bodily functions such as growth, development,
and reproduction
Trang 6Most males who have learning disabilities and/orbehavior problems due to XYY syndrome have an excel-lent prognosis Learning disabilities are mild and mostaffected males learn how to control their impulsivenessand other behavior problems XYY syndrome does notshorten lifespan
Resources PERIODICALS
Gotz, M.J., et al “Criminality and Antisocial Behaviour in Unselected Men with Sex Chromosome Abnormalities.”
Psychological Medicine 29 (1999): 953–962.
Linden M.G., et al “Intrauterine Diagnosis of Sex
Chromosome Aneuploidy.” Obstetrics and Gynecology 87
Chromosome studies can be done after birth on a skin or
blood sample to confirm the condition This syndrome
can also be diagnosed coincidentally when a pregnant
mother undergoes prenatal testing for other reasons, such
as being age 35 or older at the time of delivery Prenatal
tests that can determine whether or not an unborn baby
will be affected with 47,XXY are the chorionic villi
sam-pling (CVS) and amniocentesis procedures Both
proce-dures are associated with potential risks of pregnancy
loss and therefore are only offered to women who have
an increased risk of having a baby born with a
chromo-some problem or chromo-some type of genetic condition
Treatment and management
Treatment and management for most men with XYY
syndrome is not indicated However, early identification
and intervention of learning disabilities and/or behavior
difficulties is necessary Speech therapy, physical
ther-apy, and occupational therapy may be helpful for males
with XYY syndrome Also, because males with XYY
syndrome are at risk in stressful environments, a
support-ive and stimulating home life is important
Trang 7I Zellweger syndrome
Definition
Zellweger syndrome refers to an inherited condition
that is present at birth and usually causes death during
the first six to twelve months of age This syndrome is
caused by a lack or reduction of peroxisomes, which are
specialized organelles that help the body get rid of toxic
substances Zellweger syndrome is a disorder of
metab-olism It is one of a group of genetic disorders called
the leukodystrophies, diseases that involve abnormal
growth of the fatty covering of nerve fibers (myelin
sheath)
Description
In 1964, reserchers described a similar pattern of
multiple birth defects in two unrelated pairs of siblings in
Iowa and Maryland Hans Zellweger identified the cases
in Iowa Passarge and McAdams reported several similar
cases and introduced the name
cerebro-hepato-renal-syn-drome Opitz reviewed the Bowen report and decided
that only the Iowa cases represented the same condition
reported by others To recognize Hans Zellweger’s role in
identifying the Iowa cases, Opitz proposed the name
Zellweger cerebro-hepato-renal syndrome Most refer to
the syndrome as Zellweger syndrome
Initially, Zellweger syndrome was considered a
mul-tiple congenital anomaly disorder In 1973, researchers
reported that individuals who have Zellweger syndrome
do not have peroxisomes in their liver and kidneys
Important metabolic processes take place in
peroxi-somes Thus, the first evidence that Zellweger syndrome
should be reassigned to the metabolic disease category
was provided
Metabolism includes numerous chemical processes
involved in both construction (anabolism) and break
any enzymes are missing in the process, a build-up of aninitial substance, or a missing end-product, can result.Either of these situations can lead to disease
Peroxisomes are small organelles found in cells, ticularly of the liver, kidneys, and brain Substances thatare broken down in peroxisomes include very long chainfatty acids, polyunsaturated fatty acids, dicarboxylic fattyacids, prostaglandins, and the side chain of cholesterol.When peroxisomes are absent or deficient, very longchain fatty acids, and other substances that peroxisomesnormally help to catalyze, begin to build up in the body.Peroxisomes also play a part in the initial reactions
par-in the creation of plasmalogens Plasmalogens are tant components in the structure of myelin, a fatty layerthat covers the nerve fibers in the body This coveringhelps the nerve signals to move correctly from place to
impor-Z
K E Y T E R M SAmniocentesis—A procedure performed at 16–18
weeks of pregnancy in which a needle is insertedthrough a woman’s abdomen into her uterus todraw out a small sample of the amniotic fluid fromaround the baby Either the fluid itself or cells fromthe fluid can be used for a variety of tests to obtaininformation about genetic disorders and othermedical conditions in the fetus
Chorionic villus sampling (CVS)—A procedure
used for prenatal diagnosis at 10–12 weeks tion Under ultrasound guidance a needle isinserted either through the mother’s vagina orabdominal wall and a sample of cells is collectedfrom around the fetus These cells are then testedfor chromosome abnormalities or other geneticdiseases
Trang 8gesta-deficiency in plasmalogens Since the plasmalogens are
required for the formation of myelin, the myelin is
defec-tive
Bile acid formation also requires peroxisomes Bile
is secreted by the liver and stored in the gallbladder It is
released when fat enters the intestines Bile then helps to
break down these fats to prepare them for further
diges-tion Bile acid is produced during the breakdown of
cho-lesterol
Babies with Zellweger syndrome have severe
devel-opmental retardation and impairment of their central
nervous system They lack muscle tone (hypotonia), and
are often blind or deaf They have a distinctive facial
appearance, an enlarged liver, and may have cysts in their
kidneys They will frequently have jaundice in the
new-born period that is more serious and lasts longer than
usual Jaundice is a yellow discoloration of the skin and
eyes caused by too much bilirubin in the blood It may be
a symptom of many disorders including liver disease
Healthy newborns frequently have jaundice that resolves
after a few days
Genetic profile
Zellweger syndrome is an autosomal recessive
con-dition This means that in order to have the condition, an
individual needs to inherit one copy of the gene for
Zellweger syndrome from each parent An individual
who has only one copy of the gene is called a carrier for
the condition and does not have any signs or symptoms
of the condition When two parents are carriers for
Zellweger syndrome, they have a 25% chance, with each
pregnancy, for having an affected child They have a 50%
chance for having a child who is a carrier for the
condi-tion and a 25% chance for having a child who is neither
affected nor a carrier for Zellweger syndrome
Changes or mutations in any of several different
genes involved in the creation of peroxisomes
(peroxi-some biogenesis) can cause Zellweger syndrome There
are many gene mutations that have been identified that
are involved with the creation of functioning
peroxi-(short arm of chromosome 2 at 2p15), peroxisome genesis factor 6 (short arm of chromosome 6 at 6p21),peroxisome assembly factor-1 (long arm of chromosome
bio-8 at bio-8q21), peroxisomal targeting signal 1 receptor (shortarm of chromosome 12 at 12p13), and peroxisome bio-genesis factor 10 (chromosome 1)
The cause of Zellweger syndrome is a failure of theperoxisomes to be able to bring newly created peroxiso-mal proteins into the peroxisomes Instead, the proteinsstay outside of the peroxisomes and are broken down.The peroxisome membranes may be present, but areempty, like the wood frame of an empty house Theseempty peroxisomes have been called peroxisome
“ghosts.”
Demographics
The frequency of this condition is estimated to be 1
in 50,000 There is no reported difference in the dence in any particular sex or ethnic background
inci-Signs and symptoms
The characteristic facial features of Zellweger drome include:
syn-• high forehead
• widely spaced eyes (hypertelorism)
• low, broad, or flat nasal bridge
• “full” cheeks
• small chin (micrognathia)
• forward tilting (anteverted) nostrils
• vertical fold of skin over the inner corner of the eye(epicanthal fold)
• upslanting eyes
• shallow orbital ridges
• minor ear abnormalitiesOther characteristics include, but are not limited to:
• breech presentation at birth (feet first)
Trang 9• gastrointestinal bleeding
• slow growth after birth
• severe mental retardation
• abnormal brain findings
• involuntary, rhythmic movements of the eyes
(nystagmus)
• large space between the bones of the skull (fontanel)
• flat back part of the head (occiput)
• tiny white or yellow spots on the colored part of the
eyes (brushfield spots)
• redundant skin on neck
• congenital cloudy lenses of the eye (cataracts)
• possible heart defects
• a single crease across the palm of the hands (simian
creases)
• fixed, immovable joints (contractures)
• misaligned bones in the front part of the foot/club foot
(talipes equinovarus)
• undescended testicles (cryptorchidism)
• underdeveloped thymus (thymus hypoplasia)
Diagnosis is based on clinical characteristics
com-bined with a series of tests to determine the peroxisomal
function and structure Biochemical abnormalities
include elevated levels of very long chain fatty acids, a
decrease in the levels of a peroxisomal enzyme
dihy-droxyacetone phosphate acyltransferase (DHAPAT), the
presence of abnormal intermediates in bile acid
forma-tion, and a lack of plasmalogens in a blood sample
Absence of peroxisomes in liver biopsy specimen is
con-sidered essential for the diagnosis of Zellweger
syn-drome
Prenatal diagnosis for Zellweger syndrome is
possi-ble through chorionic villus sampling (CVS) and
amnio-centesis Diagnosis may be made by measuring the
synthesis of plasmalogens in cultured CVS or amniotic
fluid cells or by measuring the amount of very long chain
fatty acids Other tests may be useful, including
measur-There are other leukodystrophies, including neonataladrenoleukodystrophy, infantile Refsum disease, and
hyperpipecolic acidemia The milder diseases may bedue to having partial peroxisome function
Treatment and management
In general there is no cure and no treatment forZellweger syndrome
Prognosis
The prognosis for individuals who have Zellwegersyndrome is poor Those with the disease usually onlylive for a few months after birth Rarely do individualswith Zellweger syndrome live longer than one year
Resources BOOKS
Jones, Kenneth Lyons, ed Smith’s Recognizable Patterns of Human Malformation 5th ed Philadelphia: W.B.
Saunders Company, 1997.
ORGANIZATIONS
National Organization for Rare Disorders (NORD) PO Box
8923, New Fairfield, CT 06812-8923 (203) 746-6518 or (800) 999-6673 Fax: (203) 746-6481 ⬍http://www
.rarediseases.org ⬎.
United Leukodystrophy Foundation 2304 Highland Dr., Sycamore, IL 60178 (815) 895-3211 or (800) 728-5483 Fax: (815) 895-2432 ⬍http://www ulf.org⬎.
in the formation of a new person
Description
Trang 10tilizing the egg The membranes of the egg and sperm
combine, producing one single cell The egg and sperm
prepare to fuse their genetic material
(DNA/chromo-somes) Finally, the genetic material combines to
pro-duce the zygote with one complete set of chromosomes
Most cells in the human body have two pairs of 23
chromosomes, i.e 46 chromosomes total One set of 23
chromosomes is inherited from the mother, and the
complementary set is inherited from the father When
the egg and sperm are formed, the two sets of
chromo-somes divide evenly, from 46 to 23 chromchromo-somes to
pro-duce eggs and sperm with 23 chromosomes each This
ensures that when the egg and sperm fuse during
con-ception, the original number of chromosomes (46) is
restored
The reduction of each parent cell from 46 to 23
chro-mosomes ensures that each parent contributes half of his
or her genetic material to form the zygote and the
off-spring shares 50% of his or her genes with each parent
Duplication of the single zygote occurs through a
com-Approximately six days after fertilization, the ball ofcells attaches to the uterine wall
Sex determination
Men and women each have 22 pairs of non-sex mosomes and two sex chromosomes Men’s sex chromo-somes are X and Y A mature sperm cell that hasundergone the chromosome division process from 46 to
chro-23 chromosomes produces a cell that is either X or Y.Women’s sex chromosomes are X and X The eggs thatwomen produce have only X chromosomes Therefore,the sperm determines whether the zygote is XY or XX,which is the initial step on the biological path to becom-ing a male or female
Developmental periods
The term embryo refers to the developing baby
between the second week after conception and the eighth
week after conception Doctors use the term fetus from
the ninth week after conception to birth A pregnancy isbroken down into three trimesters The first trimesterbegins with the first day of the woman’s last menstrual
period and each trimester is three calendar months.
Twins
Twins may arise in two ways Identical twins arecalled “monozygotic” because both individuals areformed from the same zygote As the zygote divides toform the baby, two separate individuals form instead ofone Fraternal twins are called “dizygotic” because eachindividual develops from a different zygote Two eggs areovulated, and a separate sperm fertilizes each egg.Therefore, identical twins have exactly the same DNA ineach cell and fraternal twins share the same amount ofDNA as brothers and sisters Sometimes it is impossible
to tell monozygotic twins from dizygotic twins based onthe placenta and the fetal membranes If a person wants
to determine whether twins are monozygotic or gotic, DNA studies of blood cells will provide a defini-tive answer
Chromosome—A microscopic thread-like
struc-ture found within each cell of the body and
con-sists of a complex of proteins and DNA Humans
have 46 chromosomes arranged into 23 pairs
Changes in either the total number of
chromo-somes or their shape and size (structure) may lead
to physical or mental abnormalities
Gene—A building block of inheritance, which
contains the instructions for the production of a
particular protein, and is made up of a molecular
sequence found on a section of DNA Each gene is
found at a precise location on a chromosome
Teratogen—Any drug, chemical, maternal disease,
or exposure that can cause physical or functional
defects in an exposed embryo or fetus
Trang 11Abnormalities can also arise when the zygote begins
to divide This type of abnormality is usually severe,
eventually leading to a miscarriage If an abnormality
occurs after the zygote has divided one or more times, the
baby will have some normal cells and some abnormal
cells This situation is referred to as “mosaicism” and
“mosaic” may be used to describe the person’s condition
Molar pregnancies
Molar pregnancies can occur in one of two ways
Sometimes the original cell that duplicates and divides to
form the fetus is completely of paternal origin The
chro-mosomes in a sperm duplicate themselves, then proceed
to divide as if they were a normal zygote These
preg-nancies are completely abnormal and miscarry Another
type of molar pregnancy occurs when two sperm fertilize
one egg The zygote is triploidy and has 69 chromosomes
instead of 46 Although some fetal parts can be seen,
these pregnancies normally miscarry in the first or
sec-ond trimester
Birth defects
The term birth defect describes many different types
of abnormalities, including physical malformations
Abnormalities of anatomical structures may be
signifi-cant or insignifisignifi-cant; minor variations in structure are
common Approximately 3% of newborns have major
malformations The causes are: chromosome
abnormali-ties (6–7%), inherited genetic conditions (7-8%),
envi-ronmental factors (7–10%), and multifactorial causes
(20–25%) The cause of the remaining 50–60% of
mal-formations is unknown Multifactorial refers to causes
with both genetic and environmental components
Environmental factors include exposures to drugs,
chem-icals, or other substances that affect the development of
the fetus while he/she is in the uterus Substances that
cause birth defects are referred to as teratogens
Artificial reproductive technology
Couples may pursue assisted reproductive
technolo-gies for a number of reasons If a couple has artificial
insemination, the sperm is inserted into the uterus when
the woman in ovulating Fertilization then occurs as it
would normally If a couple has in vitro fertilization
(IVF), the egg and sperm are mixed outside the body in
the laboratory The zygote forms in a petri dish if
fertil-ization occurs After a number of cell divisions, the
developing embryo is placed in the woman’s uterus If
the sperm are incapable of fusing with the egg
them-selves, the sperm may be injected into the egg This
addi-In the year 2001, preimplantation diagnosis is
pos-sible for a number of genetic diseases Couples maypursue this if they are at a significant risk for having achild with a disease that could be diagnosed prior tobecoming pregnant through preimplantation diagnosis.The procedure is like that of in vitro fertilization, with
an additional step After fertilization occurs and thezygote has begun to divide, a single cell is removed.Removing the cell does not harm the other cells Thecell that is removed is tested for the genetic disease forwhich the couple is at risk Multiple developingembryos are tested Only the embryos that do not havethe condition are placed in the woman’s uterus to com-plete development
The development of a person from the zygote is afascinating and amazing process It is a difficult area tostudy because scientists cannot manipulate humanembryos to observe the effects, and the development ofthe fetus cannot be directly observed Researchers stillhave many unanswered questions Following a doctor’srecommendations from prior to the pregnancy through-out pregnancy (such as folic acid intake and avoidance
of alcohol and other drugs) increases the chances thatthe development of a zygote into a full-term infant will
be normal However, there are many babies born withsevere birth defects or genetic diseases despite the par-ents’ efforts at doing everything in their power to pre-vent a problem Most birth defects and genetic
A human zygote.(Photo Researchers, Inc.)
Trang 12BOOKS
Agnew, Connie L Twins!: Expert Advice From Two Practicing
Physicians on Pregnancy, Birth, and the First Year New
York: HarperCollins, 1997.
Brasner, Shari E Advice From a Pregnant Obstetrician New
York: Hyperion, 1998.
Nathanielsz, P.W Life in the Womb: The Origin of Health and
Disease Ithaca, NY: Promethean Press, 1999.
Vaughn, Christopher C How Life Begins: The Science of Life in
the Womb New York: Times Books, 1996.
Kowalski, Kathiann “High-tech Conception in the 21st
Century.” Current Health (January 2000): 1–4.
Miller, Annetta, and Joan Raymond “The Infertility
Challenge.” Newsweek (Spring/Summer 1999 Special
.org ⬎.
RESOLVE, The National Infertility Association 1310 Broadway, Somerville, MA 02144-1779 (617) 623-0744 resolveinc@aol.com ⬍http://www.resolve.org⬎.
Trang 13Pedigree charts are a visual tool for documenting
biological relationships in families and the presence of
disorders Using these charts, a medical professional
such as a geneticist or genetic counselor, can analyze the
genetic risk in a family for a particular trait or condition
by tracking which individuals have the disorder and
determining how it is inherited
A standard set of symbols has been established foruse in creating pedigree charts Those found within thebody of several entries in the encyclopedia follow thesymbol guide explained on the next page The exact styleand amount of information presented on the chart variesfor each family and depends on the trait or conditionunder investigation Typically, only data that is directlyrelated to the disorder being analyzed will be included
SYMBOL GUIDE FOR PEDIGREE CHARTS
Trang 14Symbol Guide for Pedigree Charts
Gender not specified
Male adopted into
a family
Female adopted into
a family
Pregnancy P
Four males 4
Three females 3
Identical twin females
Fraternal twin females
Consanguineous relationship Relationship no longer exists
Unknown family history
Female with no children
by choice
Symbol Guide for Pedigree Charts
Trang 15A chromosome map indicates the relative positions
of the genes that code for certain characteristics The
basic format for writing a gene position is the
chromo-some number, arm, band, sub-band, and sub-sub-band, if
known An example is 3p22.5
The chromosome number refers to one of the 22
autosomal chromosomes (numbered 1-22) or one of the
sex-determining chromosomes known as X or Y In the
example, the gene is on chromosome 3
Each chromosome has two arms, separated by a
cen-tromere, the pinched-in area toward the top of the
chro-mosome The short arm, labeled “p”, is above the
centromere and the long arm, “q”, is below it In the case
of the example gene, it is found on the short arm (p) of
chromosome 3, or 3p
The arms are further divided into cytogenetic bands
(regions) numbered 1, 2, 3, etc The numbers start at the
centromere and increase to the end of the arm, known asthe telomere These bands can only be seen when stainedand viewed under a microscope Sub-bands, which arenumbered the same way as bands, may be visible withinbands at greater magnifications Therefore, the exactlocation of the example gene is the short arm (p) of chro-mosome 3, band 2, sub-band region 2, and a sub-subband 5
The following 24 illustrations demonstrate theapproximate gene location for several of the genes relat-ing to disorders mentioned in this encyclopedia.Disorders known to be related to a specific chromosomebut not necessarily at an exact location have been placedbelow the chromosome These chromosome maps are in
no way complete, rather, they provide an introduction tounderstanding relative size differences of human chro-mosomes and where geneticists have located the genesassociated with the source of certain genetic disorders
CHROMOSOME MAP
Trang 1622 21 16 15 14 13 12 11
12 11
13
1 1
33
37
32
34 35 36
24
31
23 22 21 14
2
Spastic cerebral palsy
Chromosome 2
Trang 17hMLH1: Muir-Torre syndrome
HGD: Alkaptonuria (3p) LAR1: Larsen syndrome (3p)
13 12 11 11 12 13
2
1
HD: Huntington disease
MPS: Mucopolysaccharidoses Achondroplasia
RIEG: Rieger syndrome
p q
25
27
31
33 34 35 32 28
24
26
23 22 21
3
1
LQT4: Long QT syndrome 4 alpha-synuclein: Parkinson disease
Chromosome 4
EVC: Ellis-van Creveld
Trang 18Chromosome 5
CSA: Cockayne syndrome
SRD51A: Steroid 4-alpha reductase 1 Cri du chat syndrome
22 23 24 25
21
12 11 11 12 13 14 15 16
1 2
p q
23 24
25 26 27
22 21
SCA1: Spinocerebellar atrophy
COL11A2: Weissenbacher-Zweymuller syndrome
Trang 19GCK: Diabetes
23 22
12
12 13
11 21
11
1 2
p q
23
24
22 21
1
2
Cohen syndrome
Klippel-Feil syndrome Hereditary spherocytosis
Chromosome 8
MYC: Burkitt lymphoma LGS: Langer-Giedon syndrome WRN: Werner syndrome
11
11
1
p q
22
26 25
21
23 24
Trang 2011 11
1
p q
14 15
24 23
13 12
21 22
BRCA2: Breast cancer
ATP7B: Wilson disease RB1: Retinoblastoma
12 13
11
11
1
p q
21
32 31
13 12
22 23 24
1
3 2
Chromosome 14
PS1(AD3): Alzheimer disease Krabbe disease
Trang 21SOX9: Campomelic dysplasia
LCA1: Leber congenital amaurosis, Type 1
p
q
12 13
11 11
1
p q
24 23
13 12 21 22
ABCC6: Pseudoaxanthoma elasticum (16)
FMF: Familial Mediterranean fever
11
11
1
p q
23
12 21 22
CDMP1: Brachydactyly
11 12 13
11
1
p q
12 13
1
Trang 22PIG-A: Paroxysomal nocternal hemoglobinuria
Chromosome X
Asplenia (x)
KAL: Kallman syndrome (x)
12 13
11
11
1
p q
12 13
Trang 23A-T Children’s Project
668 South Military Trail
Deerfield Beach, FL 33442
Phone: (800) 5-HELP-A-T
Website: http://www.atcp.org
A-T Medical Research Foundation
5241 Round Meadow Road
Fax: (210) 490-7161 or (210) 497-3810 Website: http://www.amda-pompe.org
Agenesis of the Corpus Callosum (ACC) Network
University of Maine Merrill Hall, Room 18, 5749 Orono, ME 04469-5749 Phone: (207) 581-3119 E-mail: um-acc@maine.edu
Aicardi Syndrome Awareness and Support Group
29 Delavan Ave.
Toronto, ON M5P 1T2 Canada
Phone: (416) 481-4095
Aicardi Syndrome Foundation
450 Winterwood Dr.
Roselle, IL 60172 Phone: (800) 373-8518.
Website: http://www.aicardi.com
AIS Support Group (AISSG)
PO Box 269, Banbury Oxon, OX15 6YT United Kingdom Website: http://www.medhelp.org/
Phone: (800) 432-7543 Website: http://www.agbell.org
Allergy and Asthma Network Mothers of Asthmatics, Inc.
2751 Prosperity Ave., Suite 150 Fairfax, VA 22031
Phone: (800) 878-4403 Fax: (703) 573-7794
Alliance of Genetic Support Groups
4301 Connecticut Ave NW, Suite 404 Washington, DC 20008
Phone: (202) 966-5557 Fax: (202) 966-8553 Website: http://www.geneticalliance org
Alpha 1 National Association
8120 Penn Ave South, Suite 549 Minneapolis, MN 55431 Phone: (612) 703-9979 or (800) 521- 3025
E-mail: julie@alpha1 Website: http://www.alpha1.org
Alpha One Foundation
2937 SW 27th Ave., Suite 302, Miami, FL 33133.
Phone: (305) 567-9888 or (877) 7321.
228-E-mail: mserven@alphaone.
Website: http://www.alphaone.org
Alpha to Alpha
RR#5 Box 859 Warsaw, MO 65355 Phone: (660) 438-3045 Website: http://www.alpha2alpha.org
ORGANIZATIONS
The following is an alphabetical compilation of organizations listed in the Resources section of the main body entries.
Although the list is comprehensive, it is by no means exhaustive It is a starting point for further information, as well as otheronline and print sources Many of the organizations listed provide information for multiple disorders and have links to addi-tional related websites E-mail addresses and web addresses listed were provided by the associations; Gale Group is notresponsible for the accuracy of the addresses or the contents of the websites
Trang 24ALS Association of America (ALSA)
27001 Agoura Road, Suite 150
American Academy of Allergy,
Asthma & Immunology
American Academy of Dermatology
PO Box 4014, 930 N Meacham Road
2945 W Farwell Ave.
Chicago, IL 60645-2925 Phone: (773) 761-5298 or (888) 466- 5747
Fax: (773) 761-5298 E-mail: aaksis@aaksis.org Website: http://www.aaksis.org
American Association for Pediatric Ophthalmology and Strabismus
American Association of Kidney Patients
100 S Ashley Dr., Suite 280 Tampa, FL 33602
Phone: (800) 749-2257 Website: http://www.aakp.org
American Association on Mental Retardation (AAMR)
444 North Capitol Street NW, Suite 846
Washington, DC 20001-1512 Phone: (800) 424-3688.
Website: http://www.aamr.org
American Cancer Society
1599 Clifton Road NE Atlanta, GA 30329 Phone: (800) 227-2345 Website: http://www.cancer.org
American Cleft Palate-Craniofacial Association
104 South Estes Dr., Suite 204 Chapel Hill, NC 27514 Phone: (919) 993-9044 Fax: (919) 933-9604
American Council of the Blind
1155 15th Street NW, Suite 720 Washington, DC 20005 Phone: (202) 467-5081 or (800) 424- 8666
Website: http://www.acb.org
American Diabetes Association
1701 N Beauregard Street Alexandria, VA 22311 Phone: (703) 549-1500 or (800) 342- 2383
Website: http://www.diabetes.org
American Epilepsy Society
342 North Main Street West Hartford, CT 06117 Phone: (860) 586-7505 Fax: (860 586-7550 E-mail: info@aesnet Website: http://www.aesnet.org
American Foundation for the Blind
11 Penn Plaza, Suite 300 New York, NY 10001 Phone: (800) 232-5463
American Foundation for Urologic Disease, Inc.
1128 North Charles Street Baltimore, MD 21201-5559 Phone: (410)468-1808 Website: http://www.afud.org
American Hair Loss Council
Phone: (888) 873-9719 Website: http://www.ahlc.org
American Heart Association
7272 Greenville Ave.
Dallas, TX 75231-4596 Phone: (214) 373-6300 or (800) 242- 8721
E-mail: inquire@heart Website: http://www.americanheart.org
American Hemochromatosis Society, Inc.
777 E Atlantic Ave., PMB Z-363 Delray Beach, FL 33483-5352
Trang 25American Optometric Association
243 North Lindbergh Boulevard
American Society for Reproductive Medicine
1209 Montgomery Highway Birmingham, AL 35216-2809 Phone: (205) 978-5000 E-mail: asrm@asrm Website: http://www.asrm.org
American Society of Human Genetics
9650 Rockville Pike Bethesda, MD 20814-3998 Phone: (301) 571-1825 Website: http://www.faseb.org/genetics/
ashg/ashgmenu.htm
American Society of Hypertension
515 Madison Ave., Suite 1212 New York, NY 10022 Phone: (212) 644-0600 Website: http://www.ash-us.org
American Syringomelia Project
PO Box 1586 Longview, TX 75606-1586 Phone: (903) 236-7079
American Thyroid Association
PO Box 1836 Falls Church, VA 22041-1836 Phone: (410) 243-4483 Fax: (703) 998-8893 Website: http://www.thyroid.org
Anemia Institute for Research and Education
151 Bloor Street West, Suite 600 Toronto, ON M5S 1S4
Canada Phone: (877) 99-ANEMIA Website: http://www.anemiainstitute net
Angelman Syndrome Foundation
414 Plaza Dr., Suite 209 Westmont, IL 60559-1265
Website: http://www.angelman.org
Anxiety Disorders Association of America
11900 Parklawn Dr., Suite 100 Rockville, MD 20852 Phone: (301) 231-9350 Fax: (301) 231-7392 E-mail: anxdis@adaa.org
Apert Syndrome Support Group
8708 Kathy
St Louis, MO 63126 Phone: (314) 965-3356
Aplastic Anemia Foundation
PO Box 613 Annapolis, MD 21404-0613 Phone: (800) 747-2820 Website: http://www.aplastic.org
Arc (A National Organization on Mental Retardation)
1010 Wayne Ave., Suite 650 Silver Spring, MD 20910 Phone: (800) 433-5255 Website: http://www.tharclink.org
Arc of the United States (formerly Association for Retarded Citizens
of the US)
500 East Border Street, Suite 300 Arlington, TX 76010
Phone: (817) 261-6003 Website: http://thearc.org
Arc’s Fetal Alcohol Syndrome Resource Guide
The Arc’s Publication Desk
3300 Pleasant Valley Lane, Suite C, Arlington, TX 76015
Phone: (888) 368-8009 Website: http://www.thearc.org/misc/ faslist.html
Arthritis Foundation
1330 West Peachtree Street Atlanta, GA 30309 Phone: (800) 283-7800 Website: http://www.arthritis.org
The Arthrogryposis Group (TAG)
1 The Oaks, Gillingham Dorset, SP8 4SW United Kingdom Phone: 01-747-822655 Website: http://tagonline.org.uk
Association for Glycogen Storage Disease (United Kingdom)
Trang 26Association for Macular Diseases,
Ataxia MJD Research Project, Inc.
875 Mahler Road, Suite 161 Burlingame, CA 94010-1621 Phone: (650) 259-3984 Fax: (650) 259-3983 Website: http://www.ataxiamjd.org
Autism Research Institute
4182 Adams Ave.
San Diego, 92116 Fax: (619) 563-6840
Autism Society of America
7910 Woodmont Ave Suite 300 Bethesda, MD 20814-3015 Phone: (301) 657-0881 or (800) 3- AUTISM
Website: http://www.autism-society.org
AVENUES National Support Group for Arthrogryposis Multiplex Congenita
PO Box 5192 Sonora, CA 95370 Phone: (209) 928-3688 E-mail: avenues@sonnet.com Website: http://www.sonnet.com/
avenues
Bachmann-Strauss Dystonia &
Parkinson Foundation, Inc.
Mount Sinai Medical Center, One Gustave L Levy Place, Box 1490 New York, NY 10029
Phone: (212) 241-5614 Website: http://www.dystonia- parkinsons.org
Battens Disease Support and Research Association
2600 Parsons Ave.
Columbus, OH 43207 Phone: (800) 448-4570 Website: http://www.bdsra.org
Beckwith-Wiedemann Support Network
Boys Town National Research Hospital
555 N 30th Street Omaha, NE 68131 Phone: (402) 498-6749 Website: http://www.boystown.org/ Btnrh/Index.htm
Canadian Hemophilia Society
625 President Kennedy, Suite 1210 Montreal, QUE H3A 1K2 Canada
Phone: (514) 848-0503 Fax: (514) 848-9661 E-mail: chs@hemophilia.ca Website: http://www.hemophilia.ca/ english/index.html
Canadian Multiple Endocrine Neoplasia Type 1 Society, Inc (CMEN)
PO Box 100 Meota, SK S0M 1X0 Canada
Phone: (306) 892-2080
Canadian Opitz Family Network
Box 892 Errington, BC V0R 1V0 Canada
Phone: (250) 954-1434 Fax: (250) 954-1465 E-mail: opitz@apollos.net Website: http://www.apollos.net/arena/ opitz/start.html
Canadian Society for Mucopolysaccharide and Related Diseases
PO Box 64714 Unionville, ON L3R-OM9 Canada
Phone: (905) 479-8701 or (800) 1846
667-Website: http://www.mpssociety.ca
Trang 27Education Foundation, Inc.
3962 Van Dyke Street
White Bear Lake, MN 55110
Center for Neurologic Study
9850 Genesee Ave., Suite 320
Center for Study of Multiple Birth
334 E Superior Street, Suite 464
Chicago, IL 60611
Phone: (312) 266-9093
Website: http://www.multiplebirth.com
Centers for Disease Control
Office of Genetics and Disease
Fax: (610) 499-9267 E-mail: cmtassoc@aol.com Website: http://www.charcot-marie- tooth.org
CHARGE Family Support Group
82 Gwendolen Ave.
London, E13 ORD United Kingdom Phone: 020-8552-6961 Website: http://www.widerworld.co.uk/
charge
CHARGE Syndrome Foundation
2004 Parkade Boulevard Columbia, MO 65202-3121 Phone: (800) 442-7604 Website: http://www.chargesyndrome org
CHASER (Congenital Heart Anomalies Support, Education, and Resources)
2112 North Wilkins Road Swanton, OH 43558 Phone: (419) 825-5575 Website: http://www.csun.edu/
~hfmth006/chaser
Cherub Association of Families &
Friends of Limb Disorder Children
8401 Powers Road Batavia, NY 14020 Phone: (716) 762-9997
Children Living with Inherited Metabolic Diseases
The Quadrangle, Crewe Hall, Weston Road, Crewe
Cheshire, CW1-6UR United Kingdom Phone: 127 025 0221 Fax: 0870-7700-327 Website: http://www.climb.uk
Children’s Blood Foundation
333 East 38th Street, Room 830 New York, NY 10016-2745 Phone: (212) 297-4336 E-mail: cfg@nyh.med.cornell.edu
Children’s Brain Disease Foundation
7701 95th Street Pleasant Prairie, WI 53158 Phone: (847) 433-498 Website: http://www.cbbf.org
Children’s Craniofacial Association
PO Box 280297 Dallas, TX 75243-4522 Phone: (972) 994-9902 or (800) 535- 3643
E-mail: contactcca@ccakids.com Website: http://www.ccakids.com
Children’s Gaucher Research Fund
PO Box 2123 Granite Bay, CA 95746-2123 Phone: (916) 797-3700 Fax: (916) 797-3707 Website: http://www.childrensgaucher org
Children’s Mitochondrial Disease Network
Mayfield House, 30 Heber Walk, Chester Way,
Northwich, CW9 5JB United Kingdom Phone: 01606 44733 Website: http://www.emdn-mitonet.co uk
Choroideremia Research Foundation
23 E Brundreth Street Springfield, MA 01109 Website: http://www.choroideremia.org
Chromosome 18 Registry and Research Society
6302 Fox Head San Antonio, TX 78247 Phone: (210) 567-4968 Website: http://www.chromosome18 org
Chromosome Deletion Outreach, Inc.
PO Box 724 Boca Raton, FL 33429-0724 Phone: (561) 391-5098 or (888) 236- 6880
Fax: (561) 395-4252 E-mail: cdo@worldnet.att.net Website: http://members.aol.com/
Trang 28Coalition for Heritable Disorders of
Congenital Heart Anomalies
Support, Education, and
Congenital Heart Disease
Information and Resources
Council of Regional Networks for Genetic Services
Genetic Services Program, Wadsworth Center Labs & Research
PO Box 509, Room E299, Empire State Plaza
Albany, NY 12201-0509 Phone: (518) 474-7148 Website: http://www.cc.emory.edu/
PEDIATRICS/corn/corn.htm
Craniosynostosis and Parents Support (CAPS)
2965-A Quarters Quantico, VA 22134 Phone: (877) 686-CAPS or (703) 445- 1078
Website: http://www.caps2000.org/
Creutzfeldt-Jakob Disease Foundation, Inc.
PO Box 611625 Miami, FL 33261-1625 Fax: (954) 436-7591 Website: http://www.cjdfoundation.org
Cri du Chat Society
Dept of Human Genetics, Box 33, MCV Station,
Richmond VA 23298 Phone: (804) 786-9632
Cri du Chat Syndrome Support Group
Website: http://www.cridchat.u-net.com
Crouzon Support Network
PO Box 1272 Edmonds, WA 98020 E-mail: penny@crouzon Website: http://www.crouzon.org
Crouzon’s/Meniere’s Parent Support Network
Cystic Fibrosis Foundation
6931 Arlington Road Bethesda, MD 20814 Phone: (301) 951-4422 Website: http://www.cff.org
Cystinosis Foundation
2516 Stockbridge Dr.
Oakland, CA 94611 Phone: (800) 392-8458 Website: http://www cystinosisfoundation.org
Cystinosis Research Network
8 Sylvester Road Burlington, MA 01803 Phone: (866) CURE NOW Fax: (781) 229-6030 Website: http://www.cystinosis.org
Dandy-Walker Syndrome Network
5030 142nd Path West Apple Valley, MN 55124 Phone: (612) 423-4008
DB-LINK, Teaching Research
345 N Monmouth Ave.
Monmouth, OR 97361.
Phone: (800) 438-9376.
Website: http://www.tr.wou.edu/dblink/ about.htm
Deafness Research Foundation
575 Fifth Ave., 11th Floor New York, NY 10017 Phone: (800) 535-3323 E-mail: drf@drf
Diabetes Action Research and Education Foundation
426 C Street NE Washington, DC 20002 Website: http://www.daref.org
Dubowitz Syndrome Nationwide Support Group Network
Trang 29Dystrophic Epidermolysis Bullosa
Research Association of America
Dystrophic Epidermolysis Bullosa
Research Association of United
Kingdom, (DebRA)
13 Wellington Business Park
Dukes Ride, Crowthorne
Elhers-Danlos National Foundation
6399 Wilshire Boulevard, Suite 203 Los Angeles, CA 90048
Phone: (323) 651-3038 Fax: (323) 651-1366 Website: http://www.ednf.org
Ellis-Van Creveld Foundation
Farthingdale Farm, Hackmans Lane, Purleigh
Chelmsford, CM3 6RW United Kingdom Phone: 01-621-829675 Website: http://www.cafamily.uk/
Direct/e24.html
Endocrine Society
4350 East West Highway, Suite 500 Bethesda, MD 20814-4410 Phone: (301) 941-0200 Fax: (301) 941-0259 E-mail: endostaff@endo-society.
Epilepsy Foundation of America
4351 Garden City Dr., Suite 406 Landover, MD 20785-2267 Phone: (301) 459-3700 or (800) 332- 1000
Website: http://www epilepsyfoundation.org
European Chromosome 11q Network
Attn: Annet van Betuw Else Mauhsstraat 7
6708 NJ Wageningen Netherlands
Phone: (+31) 317-42 33 45 Fax: (+31) 317-42 69 80 Website: http://www.11q.org
European Long QT Syndrome Information Center
Ronnerweg 2 Nidau, 2560 Switzerland Phone: 04(132) 331-5835 E-mail: jmettler@bielnews.ch Website: http://www.bielnews.ch/
cyberhouse/qt/qt.html
Eye Bank Association of America
1015 18th Street NW, Suite 1010 Washington, DC 20036
Phone: (202) 775-4999 Website: http://www.restoresight.org/
Eye Cancer Network
Concordia, MO 64020 Phone: (660) 463-1355 Website: http://www.cpgnet.com/fsig nsf
FACES The National Craniofacial Assocation
PO Box 11082 Chattanooga, TN 37401 Phone: (423) 266-1632 or (800) 332- 2373
E-mail: faces@faces-cranio.
Website: http://www.faces-cranio.org/
FacioScapuloHumeral Society, Inc.
3 Westwood Road Lexington, MA 02420 Phone: (781) 860-0501 E-mail: carol.perez@fshsociety Website: http://www.fshsociety.org
Families with Moyamoya Support Network
4900 McGowen Street SE Cedar Rapids, IA 54203
Family Village
University of Wisconsin-Madison, Waisman Center
1500 Highland Ave.
Madison, WI 53705-2280 E-mail: familyvillage@waisman.wisc edu
Website: http://www.familyvillage.wisc edu/index.html
Fanconi Anemia Research Fund
1801 Willamette Street, Suite 200 Eugene, OR 97401-4030 Phone: (800) 828-4891 Website: http://www.fanconi.org
Fatty Oxidation Disorders (FOD) Family Support Group
Deb Lee Gould, MEd, Director, FOD
Trang 30Food and Drug Administration
Department of Health and Human
Footsteps Institute for Rare Diseases
624 Martin Luther King Way
Tacoma, WA 98405
Phone: (253) 383-0985 or (888)
640-4673
E-mail: rwrfsi@aol.com
Forbes Norris ALS Research Center
Caifornia Pacific Medical Center
2324 Sacramento Street
San Francisco, CA 94115
Phone: (415) 923-3604
Fax: (415) 673-5184
Forward Face, Inc.
317 East 34th Street, Room 901
New York, NY 10016
Phone: (212) 684-5860 or (800)
393-3223
Foundation Fighting Blindness
Executive Plaza 1, Suite 800, 11350
McCormick Road
Hunt Valley, MD 21031
Phone: (888) 394-3937
Website: http://www.blindness.org
Foundation for Blood Research
PO Box 190, 69 US Route One
Foundation for Osteoporosis Research and Education
300 27th Street Oakland, CA 94612 Phone: (888) 266-3015 Website: http://www.fore.org
Freeman-Sheldon Parent Support Group
509 East Northmont Way Salt Lake City, UT 84103-3324 Phone: (801) 364-7060
Friedreich’s Ataxia Research Alliance
2001 Jefferson Davis Highway #209 Arlington, VA 22202
Phone: (703) 413-4468 Website: http://www.frda.org
Genetic Alliance
4301 Connecticut Ave NW, #404 Washington, DC 20008-2304 Phone: (202) 966-5557 Helpline: (800) 336-GENE Fax: (888) 394-3937 E-mail: info@geneticalliance Website: http://www.geneticalliance org
Glanzmann’s Thrombasthenia Support Group
28 Duke Road, Newton Hyde, SK14 4JB United Kingdom Phone: 0161-368-0219
Glaucoma Foundation
Phone: (207) 594-5008 Fax: (207) 594-8802 E-mail: shurd@prodigy.net Website: http://www.ginasthma.com
Goldenhar Parent Support Network
Attn: Kayci Rush
3619 Chicago Ave.
Minneapolis, MN 55407-2603 Phone: (612) 823-3529
Goldenhar Syndrome Research & Information Fund
PO Box 61643
St Petersburg, FL 3371 Phone: (813) 522-5772 Website: http://www.goldenhar.com
Goldenhar Syndrome Support Network
9325 163 Street Edmonton, ALB T5R 2P4 Canada
Guardians of Hydrocephalus Research Foundation
2618 Avenue Z Brooklyn, NY 11235-2023 Phone: (718) 743-4473 or (800) 458- 865
Fax: (718) 743-1171 E-mail: guardians1@juno.com
Haemophelia Society—
von Willebrand Support Services
Chesterfield House, 385 Euston Road
Trang 31Deaf-Blind Youths and Adults
111 Middle Neck Road
Human Growth Foundation
997 Glen Cove Ave.
Hydrocephalus Association
870 Market Street, Suite 705 San Francisco, CA 94102 Phone: (415) 732-7040 or (888) 598- 3789
Fax: (415) 732-7044.
E-mail: hydroassoc@aol.com Website: http://www.hydroassoc.org
Hydrocephalus Foundation, Inc.
(HyFI)
910 Rear Broadway Saugus, MA 01906 Phone: (781) 942-1161 E-mail: HyFI1@netscape.net Website: http://www.hydrocephalus.org
Hydrocephalus Support Group, Inc.
PO Box 4236 Chesterfield, MO 63006-4236 Phone: (314) 532-8228 E-mail: hydrobuff@postnet.com
Hypospadias Association of America
4950 S Yosemite Street, Box F2-156 Greenwood Village, CO 80111 E-mail: hypospadiasassn@yahoo.com Website: http://www.hypospadias.net
Immune Deficiency Foundation
40 W Chesapeake Ave., Suite 308 Towson, MD 21204
Phone: (800) 296-4433 Fax: (410) 321-9165 Website: http://www.primaryimmune org
IMPACC (Intestinal Multiple Polyposis and Colorectal Cancer)
PO Box 11 Conyngham, PA 18219 Phone: (570) 788-1818
Inherited High Cholesterol Foundation
University of Utah School of Medicine
410 Chipeta Way, Room 167 Salt Lake City, UT 84104 Phone: (888) 244-2465
International Center for Fabry Disease
Department of Human Genetics
International Center for Skeletal Dysplasia
Saint Joseph’s Hospital
7620 York Road Towson, MD 21204 Phone: (410) 337-1250
International Cohen Syndrome Support Group
7 Woods Court, Brackley Northants, NN13-6HP United Kingdom Phone: (012) 80-704515
International Colour Vision Society: Forschungsstelle fuer
Experimentelle Ophthalmologie
Roentgenweg 11 Tuebingen, D-72076 Germany
Website: http://orlab.optom.unsw.edu au/ICVS
International Joseph Disease Foundation, Inc.
PO Box 2550 Livermore, CA 94551-2550 Phone: (925) 461-7550 Fax: (925) 371-1288 Website: http://www.ijdf.net
International Lesch-Nyhan Disease Association
114 Winchester Way Shamong, NJ 08088-9398 Phone: (215) 677-4206
International Myopia Prevention Association
RD No 5, Box 171 Ligonier, PA 15658 Phone: (412) 238-2101
Trang 32Johns Hopkins Hospital
600 North Wolfe Street, Blalock 1008
International Progeria Registry
IBR Department of Human Genetics
1050 Forest Hill Road
International Society for
Mannosidosis and Related
Diseases
3210 Batavia Ave.
Dublin 18 Ireland Phone: (01) 235 0900 E-mail: irss@indigo.ie
Iron Disorders Institute, Inc.
PO Box 3021 Greenville, SC 29602 Phone: (864) 241-0111 E-mail: irondis@aol.com Website: http://www.irondisorders.org
Iron Overload Diseases Association, Inc.
433 Westwind Dr.
North Palm Beach, FL 33408 Phone: (561) 840-8512 E-mail: iod@ironoverload
Ivemark Syndrome Association
52 Keward Ave., Wells Somerset, BAS-1TS United Kingdom Phone: 1-(74)967-2603
JNCL Research Fund
PO Box 766 Mundelein, IL 60060 Website: http://www.jnclresearch.org
Joubert Syndrome Foundation Corporation
Attn: Stephanie Frazer
384 Devon Drive Mandeville, LA 70448
Juvenile Diabetes Foundation International (JDF)
120 Wall Street New York, NY 10005 Phone: (212) 785-9500 x708 or (800) 533-2873
Klinefelter Syndrome and Associates, Inc.
PO Box 119 Roseville, CA 95678-0119 Phone: (916) 773-2999 or (888) 999- 9428
Fax: (916) 773-1449 E-mail: ksinfo@genetic Website: http://www.genetic.org/ks
Klinefelter’s Organization
PO Box 60 Orpington, BR68ZQ United Kingdom Website: http://hometown.aol.com/ KSCUK/index.htm
Klippel-Trenaunay Support Group
5404 Dundee Road Edina, MN 55436 Phone: (612) 925-2596
Lactic Acidosis Support Trust
1A Whitley Close, Middlewich Cheshire, CW10 0NQ United Kingdom Phone: (016) 068-37198
Langer-Giedion Syndrome Association
89 Ingham Ave.
Toronto, ON M4K 2W8 Canada
Phone: (416) 465-3029 E-mail: kinross@istar.ca