DNA TESTING
Most metabolic
disorders are inherited in an autosomal recessi=
ve
manner. Both parents would have to be gene carriers of the abnormality and =
each
parent would have to pass the affected gene on to the baby for the baby to =
be
affected. Carrier testing may be available to determine if one or both pare=
nts
have one or more abnormal genes.
Some diseases are carried on the X chromosome (X‑linked). Since
males have only one X, they demonstrate the disease. Females have two X
chromosomes. In most (but not all) cases females are usually carriers and a=
re
not affected. 50% of their male children would be affected and 50% of their
female children would be carriers.
The following list is a
compilation of DNA or special laboratory tests that were available at the t=
ime
of the publication of this book. Remember, that if there is a particular
disease that affects your family but is not on the list, then you need to
contact your health care professional and see if the testing has become
available.
ACHONDROPLASIA:
A=
utosomal dominant mode of
inheritance has been described (may approach 50%). Defect in cartilage. Often fatal in=
infants
before one year of age.
Others may live normal life span.
ALPHA-1-ANTITRYPSIN DEFICIENCY:
A= utosomal dominant mode of inhe= ritance has been described (may approach 50%).&nbs= p; The deficiency of alphatrypsin in the bl= ood is believed to be caused by reduced protease activity due to a protease inhibitor. Approximately 30 variants of alpha-1 have been described.&n= bsp; The deficiency can cause liver disease, lung disease or immune probl= ems.
ANGELMAN SYNDROME:
A= utosomal recessive (25% if both parents are gene carriers) mode of inheritance has been described. A specific typ= e of severe mental retardation where a patient may appear or act like a “h= appy puppet” meaning that the patient acts like a puppet. This type of mental retardation is caused by a loss of a portion of chromosome 15.
ASHKENAZIC GENETIC DISEASE (TAY-SACHS, GAUCHERS, CYSTIC FIBROSIS):
&=
nbsp; &nbs=
p; **In the near future=
the Askenazi panel could be expanded to include:
Bloom – Carrier risk is 1 in 100
Canavan – Carrier risk is 1 in 40
Cystic Fibrosis – Carrier risk is 1 in 25
Fanconi Anemia – Carrier risk is 1 in 89
Gaucher – Carrier risk is 1 in 15
Niemann-Pick – Carrier risk is 1 in 100
Specific metabolic diseases. Auto= somal recessive (25% if both parents are gene carriers) mode of inheritance has b= een described.
CANAVAN DISEASE: =
C=
anavan is a fatal metabolic =
blood
disease usually detected
by= 18 months, which is characterized by brain deterioration.
CYSTIC FIBROSIS(CF): CF is the most common inherited disease affecting
the
Caucasian
population with a carrier rate of 1:12. A metabolic disease causing an
abnormal= ity in exocrine glands and susceptibility to respiratory infections.
bl=
ood
disease usually detected by age 6.
A few cases of adult onset has been descr=
ibed.
BARTH SYNDROME:
X-linked
inheritance has been described (50% of males will be affected, 50% of femal=
es
will be carriers).
BECKER MUSCULAR DYSTROPHY:
X-linked inheritance h=
as
been described (50% of males will be affected, 50% of =
feamles
will be carriers). A type of progressive muscular deterioration which is similar=
but
milder than Duchenne Muscular Dystrophy.=
Symptoms usually present in early =
teens
with weakness in the lower limbs. Upper limbs later.&nb=
sp;
20-30 years of age, the patient is usually in a wheel chair.
BLOOM SYNDROME:
Autosomal ressive (25% if both parents are gene carriers) mode of inheritance has been described. Disorder character= ized growth retardation (short stature), feeding problems in infancy, red ness of skin when exposed to sunlight and underdevelo= pment of cheekbones.
CANAVAN DISEASE:
A=
utosomal recessive (25% if both
parents are gene carriers) mode of inheritance has been described. Canavan is a
fatal metabolic blood disease usually detected by 18 months, which is
characterized by brain deterioration.
CHARCOT-MARIE-TOOTH:
A=
utosomal dominant (may approach
50%), autosomal recessive (25% if both parents =
are
gene carriers) and X-linked inheritance has been described (50% of males wi=
ll
be carriers, 50% of feamles will be carriers).<=
span
style=3D'mso-spacerun:yes'> Nerve-muscle
degeneration disease.
Weakness and atrophy of muscles starts in legs and arms. Onset isusually around 12 years of age.
CITRULLINEMIA:
A= utosomal recessive (25% if both parents are gene carriers) mode of inheritance has been described. A metabolic disease caused by a deficiency in the enzyme Citrulline causing vom= iting, mental retardation and ammonia intoxication-like symptoms. Elevated levels of Citrulline can be detected in amniotic fluid at mid-trimester.
COBALAMIN C DISEASE:
A= utosomal recessive (25% if both parents are gene carriers) mode of iinheritance= has been described. Cobalamin Disease if left untreated can lead to severe acidosis, ketonuria, developmental retardation and anemia.
CONGENITAL ADRENAL HYPERPLASIA (21-HY= DROXYLASE DEFICIENCY):
A= utosomal recessive (25% if both parents are gene carriers) mode of inheritance has been described. Occurs in 1:50= 00 births. Female babies = have external genitalia that is m= asculinzed, enlagemnet of clitoris and/or penis and short s= tature. This deficiency affects the releas= e of adrenal steroids (testosterone) that leads to genital ambiguity, abnormal s= alt retention and an endocrine imbalance.
CRI-DU-CHAT “Cry of the Cat”:
Incidence of the disea=
se is
1:50,000 births. A cry resemb=
ling a
cat or kitten leads to the diagnosis.
Mental retardation, small head, cat-like cry
due to a missing piece of the top of chromosome #5.
CYSTIC FIBROSIS (CF):
A=
utosomal recessive (25% of both
parents are gene carriers) mode of inheritance has been described. The most common disease in the Caucasian population =
with
a carriers rate of 1:25. Symptoms are disruption of endocrine
function in pancreas, intestinal glands, bronchial and sweat glands and
susceptibility to lower gastrointestinal problems.
DI GEORGE:
A=
utosomal dominant (may approac=
h 50%) mode of
inheritance has been described. Di
George is caused by a 22q11 rearrangement causing low set ears, cleft palat=
e, micrognathia, abnornalities
of the aortic arch, cardiac problems and susceptibility to infections.
DUCHENNE MUSCULAR DYSTROPHY:
X-linked (50% of males=
will
be affected, 50% of females will be carriers) mode of inheritance has been
described. Progressive
muscle wasting disease, usually resulting in death before age 20.
EHLERS DANLOS SYNDROME:
A=
utosomal dominant (may approach
50%), autosomal recessive (25% if both parents =
are
gene carriers) modes of inheritance has been described. Patients exhibit symptoms of skin,=
joint
and connective tissue abnornalities, easy bruis=
ing,
joint laxity, skin hyperextensibility and colla=
gen
synthesis problems.
EPIDERMOLYSIS BULLOSA:
Autosomal dominant (may approach 50%) mode of inheritance has been described. Abnormal areas of vessel and cystic spaces forme= d in the skin that occur spontaneously or after minor trauma. The condition may vary from mild to severe.
FACTOR VIII (AHG) - ANTI-HEMOPHILIAC
GLOBULIN DEFICIENCY (HEMOPHILIA):
X-linked inheritance (=
50% of
males will be affected, 50% of females will be carriers) has been
described. Decreased
amount of a blood factor (Factor VIII) which plays a role in the clotting of
blood. Bleeding and pa=
in in
the knees, elbows,&nbs=
p;
ankles, hip, loss of cartilage and osteoporosis.
FACTOR IX (CHRISTMAS FACTOR DEFICIENC=
Y):
X-linked inheritance (=
50% of
males will be affected, 50% of females will be carriers) has been
described. Blood factor which=
plays
a role in the clotting of blood. Deficiency of Vitamin K leading to a bleeding disorder.
FACTOR XIII:
X-linked inheritance (=
50% of
males will be affected, 50% of females will be carriers) has been
described. Blood factor which=
plays
a role in the clotting of blood.
Bleeding moderate to severe, delayed heal=
ing
and clotting, scarring and CNS bleeding.
FANCONI ANEMIA Type 1 & 2:
Autosomal recessive (25=
% if
both parents are gene carriers) mode of inheritance has been described. A
disorder characterized by a failure to make new cells in the bone marrow,
possible bone abnormalities and developmental delay.
FLUORESCENT I= N-SITU HYBRIDIZATION:
Us=
e of
special stains to identify specific chromosomes or pieces of chromosomes ei=
ther
preconceptionally or prenatally.<=
span
style=3D'font-size:10.0pt;mso-bidi-font-size:12.0pt'>
FRAGILE-X SYNDROME:
X-linked inheritance (=
50% of
males will be affected, 50% of females will be carriers) has been
described. Mental
retardation in males, identified by a tendency of a small piece near the bo=
ttom
of the X chromosome which seems to separate from the rest of the X chromoso=
me
under special culture conditions.&n=
bsp;
Characteristics include long face, prominent jaw, long ears, promine=
nt
forehead, connective tissue disorders, hyperextension
of fingers, large testes and hyperactivity.
**Fragile X is the most common reason for male mental
retardation. When there is fa=
mily
history of male mental retardation on the female side of the family conside=
ration
should be given to performing Fragile X DNA (FMR: Fragile X Mental Retardation) test=
ing on
the female at risk. This test
measures the number of CGG repeats and can help detect women at risk for ha=
ving
a male child with mental retardation due to Fragile X.
If the affected male is available for testing; consider
chromosome testing, Fragile X testing and genetic evaluation if it has not =
yet
been performed.**
FRIEDRICH ATAXIA:
A=
utosomal recessive (25% if both
parents are gene carriers) hmode of inheritance=
has
been described. Progressive l=
imb
and gait ataxia usually between 8-16 years but before age 25. Symptoms include weakness of legs,
scoliosis, skeletal and cardiac abnormalities, heart problems with the loss=
of
the ability to walk within 15 years of diagnosis and death bewteen age 40-50.
GAUCHERS DISEASE:
Autosomal recessive (25% if both parents are gene carrier= s) mode of inheritance has been described.&nb= sp; Also called “glucosylceramide lipidoses” is characterized by the accumulation= of glucosylceramide.&nb= sp; Symptoms usually occur in childhood and affected individuals usually reach adulthood. Adult onset = of Gaucher’s has a normal life expectancy. Symptoms include hepatosplenomegaly and bony lesions.
GLYCEROL = KINASE DEFICIENCY:
X-linked
inheritance (50% of males will be affected, 50% of females will be carriers)
has been described. Symptoms
include elevated urinary excretion of glycerol, poor growth, mental retarda=
tion
and osteoporosis with fractures.
HOMOCYSTINURIA:
Autosomal recessive (25% if both parents are gene carrier= s) mode of inhyeitance has been described. Characterized by tall stature, scoliosis, pectus excavatu= m, myopia, dislocated lenses, arachnodactyly, ment= al retardation, vascualr thromobosis. Patient usually responds to Vitamin B6 therapy.
HUNTINGTO= N’S CHOREA:
Autsomal dominant (may approach 50%) mode of inheritance=
has
been described. Pr=
ogressive
brain deterioration which may not present until the 30’s, 40’s =
or
50’s. Disorder of ba=
sal
ganglia causing motor, cognitive and behavioral dysfunction. Other symptoms include restlessnes=
s,
clumsiness, altered speech/handwriting, a personality change and enlargemen=
t of
the lateral ventricles of the brain.
HURLER SY= NDROME:
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described.
Diagnosis is usually made during the 1st year of life, de=
ath
by age 14. Characterized
by gross facial features, enlarged skull, small stature, corneal opacities,=
valvular heart defects, thick skin, joint contracture=
s,
hernias and progressive mental degeneration. Prenatal diagnosis can be made by
measuring iduronidase activity and incorporatio=
n of labelled sulphate in glycosaminoglycans of amniotic cells.
HURLER-SC= HEIE DISEASE:
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described.
This is a milder form of Hurler.&nb=
sp;
Diagnosis by age 6, coarse facial features, corneal clouding, joint
contractures, heart murmurs, normal intelligence and outlook is good if the=
re
are no cardiac abnormalities.
KALLMAN SYNDROME:
Autosomal
dominant (may approach 50%), autosomal recessive (25% if both parents are g=
ene
carriers) and X-linked (50% of males will be affected, 50% of females will =
be
carriers) modes inheritance has been described. Characterized by anosmia,
hypogonadotrophic hypogonadism, mental deficiency, hypotelorism and renal
agenesis.
KENNEDY D= ISEASE:
X-linked
(50% of males will be affected, 50% of females will be carriers) inheritance
has been described. Muscle wa=
sting
disease, neuroendorcine syndrome of the spinal
muscular atrophies, associated with testicular atrophy and gynaecomastia
and proximal muscle selectivity.
LANGER-GI= EDION SYNDROME:
Autosomal
dominant (may approach 50%) inheritance has been described. Deletion of chromosome #8 characte=
rized
by heavy eyebrows, blubous nose, thin upper lip, microcephaly, large and po=
orly
developed ears (often deaf), sparse scalp hair, mental retardation, speech
delay, short stature and loose skin.
LESCH-NYH= AN DISEASE:
X-linked
inheritance (50% of males will be affected, 50% of females will be carriers)
has been described. Character=
ized
by neurological disorders in females, mental retardation, self-mutilation. Presents at 4-6 months since child=
can
not hold up head, motor and physical development delay. Prenatal diagnosis: motor uric acid to creatinine
in morning urine samples.
LIMB-GIRD= LE MUSCULAR DYSTROPHY:
Autosomal dominant (may app=
roach
50%) and autosomal recessive (25% if both parents are gene carriers) inheritance has been described.
LOU
GEHRIG’S DISEASE – AMYOTROPHIC LATERAL SCLEROSIS (ALS):
Autosomal dominant (may approach 50%), and autosomal recessive (25% if both parents are gene car=
riers)
inheritance has been described.
ALS is usually detected in adults (adult-onset). The disease causes progressive mus=
cle
deterioration and is considered a muscle-wasting diseas=
e Death can occur within 2-3 =
years
of symptoms. However, 10-20% =
of ALS
patients may survive 10 or more years.
MEDIUM CH=
AIN
ACYL-CoA DEHYROGENASE (MCAD):
Autosomal recessive (25% if both parents are gene carrier=
s)
mode of inheritance has been described.&nb=
sp;
Characterized by Reye-like syndrome episodes,
METHYLMAL= ONIC ACIDURIA (MMA)
Autosomal recessive (25% if both parents are gene carrier=
s)
mode of inheritance has been described.&nb=
sp;
Characterized by ketoacidos=
is,
hyperammonaemia, hepatomeg=
aly,
encephalopathy, muscle weakness, mental retardation, recurrent bacterial and
viral infections, osteoporosis, low white blood count and low platelets.
MILLER-DI= EKER:
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described.
Incomplete brain development often associated with an abnormality in=
the
upper half of chromosome #17.
Characterized by smooth brain surface with large ventricles, seizure=
s,
IUGR ( intrauterine growth retardation), loss of
muscle tone, small head and facial dysmorphism.=
MYOTONIC DYSTROPHY:
Autosomal dominant (may approach 50%) inheritance has been
described. Characterized by f=
acial
muscles, sternomastoids, distal limb muscle
weaknesses and wasting, delayed motor development and mental retardation.
NEUROFIBR= OMATOSIS:
Autosomal dominant (may approach 50%) inheritance has been
described. De=
velopment
of benign or occassionally malignant tumors alo=
ng the
course of the nerves with occassional seizures.=
Multiple skin lesions
(cafe-au lait spots) are present.
NIEMANN-P= ICK:
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described. Characterized by an abnormal accumulation of shpinogomyelin. Type I: Failure to thrive, hepatomegaly,
psychomotor deterioration and death by age 4. Type II: No neurological involvement, prolo=
nged
survival. Type III & IV:<=
span
style=3D'mso-spacerun:yes'> Death by adolescence.
NORRIE= 217;S DISEASE:
X-linked
inheritance (50% of males will be affected, 50% of females will be cariers) has been described. Characterized =
by
blindness, possible deafness or possible developmental delay. X-linked inheritance.
ORNITHINE TRANSCARBAMYLASE:
X-linked
inheritance (50% of males will be affected, 50% of females will be carriers)
has been described. Mutation =
of the
ornithine transcabamylase<=
/span>
gene leads to partial deficiency in females and complete deficiency in
males. Ch=
aracterized
by a defective OTC gene causing chronic ammonia intoxication and mental
deterioration.
OSTEOGENE= SIS IMPERFECTA:
Autosomal dominant (may approach 50%) and autosomal
recessive (25% if both parents are gene carriers) inheritance has been
described. Hereditary skeleta=
l condition
that leads to increased risk for fractures and skeletal deformity.
PATERNITY
STUDIES - AMNIOTIC FLUID:
Retrieval
and use of fetal cells suspended in the amniotic fluid to compare with a
mother’s white blood cells and those of a presumed father to determine
paternity.
PHENYLKET=
ONURIA
(PKU):
Autosomal recessive (25% if both parents are gene carreirs) minheritance ha=
s been
described. PKU is caused by an
enzyme deficiency that is characterized by mental retardation, eczema, hypopigmentation and neurological symptoms if not tre=
ated.
POLYCYSTIC
KIDNEY DISEASE:
Autosomal dominant (may approach 50%) and autosomal
recessive (25% if both parents are gene carriers) inheritance has been
described. Presence
of many and/or large cysts in one or both kidneys and/or liver.
PRADER-WI= LLI:
Chromosomal inheritance. A condition of
developmental delay and compulsive overeating leading to obesity.
PROPRIONI= C CoA:
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described. Characterized by vomiting, lthargy,
ketosis, neutropenia, thrombocytopenia, develop=
mental
retardation and intolerance to protein. Patients with this disorder have p=
uffy
cheeks and an abnormal upper lip.
RECOMBINA=
NT 8
–
Chromosomal
inheritance. Increased risk f=
or
recombinant abnormalities of chromosome #8.
RETINITIS PIGMENTOSA:
Autosomal dominant (may= approach 50%), autosomal recessive (25% if both parents = are gene carriers) and X-linked inheritance (50% of males will be affected, 50%= of females will be carriers) has been described.
Degeneration of the back of the eye (retina) which
causes reduced vision and night blindness and usually progresses to complete
loss of vision.
RETINOBLA= STOMA:
Autosomal dominant (may approach 50%) due to a deletion in
chromosome 13q has been described.&=
nbsp;
Development
of a cancer in the back of the eye. M=
ost
commonly presents in infancy, rare after age 6. 30% have both eyes affected. If not treated, could spread to the
brain, lymph nodes, CNS ans skeleton within 12 =
months
of presentation.
SICKLE CE= LL DISEASE (BLACK ANCESTRY):
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described.&nbs=
p;
Blood
disease causing anemia and blood clotting. <=
/span>Increased susceptibility to bacterial infections, poor immune
response due to sickled red blood cells.=
SMITH-LEM= LI OPITZ:
Autosomal
recessive (25% if both parents are gene carriers) inheritance has been
described. Characterized by
microcephaly, mental retardation, hypotonia, incomplete development of male
geneitalia, short stature and possible pyloric stenosis.
SMITH-MAG= ENIS SYNDROME:
Autosomal
dominant (may approach 50%) inheritance has been described A disorder caused by a chromosome
interstitoial deletion of 17p in patients.=
Characterized by brachycephaly, midface hypoplasia, horase voice, sp=
eech
delay, possible hearing loss, psychomotor and growth retardation and behavi=
oral
problems.
SPINAL MU=
SCULAR
ATROPHY (SMA):
Autosomal dom=
inant
(may approach 50%) and autosomal recessive (25%=
if
both parents are gene carriers) modes of inheritance has been described.
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described. Tay Sachs is a fatal metabolic blood disease usually
detected by age 6. A few case=
s of
adult onset has been described
THALASSEM=
IA
(ITALIAN/ASIAN ANCESTRY):
Autosomal recessive (25% if both parents are gene carrier=
s)
inheritance has been described. Deficient synthesis of one or more of the normal blood globin chains.
Blood disroder rangi=
ng from
minor to severe.
TREACHER COLLINS:
Autosomal
dominant (may approah 50%) mode of inheritance has been described. Characterized by hemifacial micros=
omia,
hypoplasia and asymetry involving mandible and ear, eye anomalies,
cardiovascular malformations and skeletal defects.
WILLIAMS SYNDROME:
Autosomal
dominant (may approach 50%) mode of inheritance has been described due to a
chromosome abnormality.
Characterized by delayed motor and perceptual development,
hypercalcemia, elfin face, mental retardation and aortic stenosis. *A new chromosomal probe is availa=
ble.
WOLF-HIRS= CHORN:
Autosomal dominant (may approach 50% mode of inheritance =
has been decsribed. Growth and mental retardation, sma=
ll
head, “Greek warrior helmet” appearing face, cleft lips and/or
cleft palate and/or heart defects. A small piece of the short arm of chromo=
some
#4 is usually absent.
**Some
of these tests listed above can only be performed on the mother and/or fath=
er
of the baby, but not on amniocytes (baby’s
amniotic fluid cells). Some of these tests are more reliable if performed on
the child after he/she is born, but many parents think that it is too late =
to
find out about a problem after the delivery. The information from these tes=
ts
may tell you if the fetus or patient is:
1. Affected with a disease =
of
trait.
2. A carrier of the disease=
or
trait.
3. Free from acquiring the
disease or trait.