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Microdeletion Syndrome |
1. Williams Syndrome
Williams syndrome is a rare genetic condition
(estimated to occur in 1/7,500 births) which causes medical
and developmental problems.
Williams syndrome was first recognized as a distinct entity
in 1961. It is present at birth, and affects males and
females equally. It can occur in all ethnic groups and
has been identified in countries throughout the world.
Patients suffer from the following syndromes:
• Characteristic facial appearance
• Heart and blood vessel problems
• Hypercalcemia (elevated blood calcium levels)
• Low birth-weight / low weight gain
• Feeding problems
• Irritability (colic during infancy)
• Dental abnormalities
• Kidney abnormalities
• Hernias
• Hyperacusis (sensitive hearing)
• Musculoskeletal problems
• Overly friendly (excessively social) personality
• Developmental delay, learning disabilities and
attention deficit
• Further reading from the UK
2. Retinoblastoma
Retinoblastoma is a childhood cancer
arising from immature retinal cells in one or both eyes
and can strike from the time a child is in the womb up
to 5 years of age. This cancer is curable if caught early
enough. However, 87% of the children stricken with this
disease worldwide die, mostly in developing countries.
In developed countries, 97% of those who do live have
moderate to severe visual impairment.
Retinoblastoma is a relatively uncommon tumor of childhood
that accounts for about 3% of the cancers in children
under the age of 15. The tumors originate in the retina,
the light sensitive layer of the eye, which enables the
eye to see. When the tumors are present in one eye, it
is referred to as unilateral retinoblastoma, and when
it occurs in both eyes it is referred to as bilateral
retinoblastoma. 60% of the cases involve only one eye
(unilateral); the rest affect both eyes (bilateral). 90%
of retinoblastoma patients have no family history of the
disease and only 10% of newly diagnosed patients have
other family members with retinoblastoma.
Early diagnosis and intervention is critical to the successful
treatment of this disease. Common signs of retinoblastoma
include:
• a white "glow" or "glint"
in the pupil of one or both eyes in dim lighting
• white pupil in a color photo
• crossed or misaligned eyes
3. Prader Willi’s Syndrome
Prader-Willi syndrome (abbreviated PWS)
is a very rare genetic disorder, in which seven genes
(or some subset thereof) on chromosome 15 are missing
or unexpressed (chromosome 15q partial deletion) on the
paternal chromosome.
Prader-Willi syndrome is also frequently associated with
an extreme and insatiable appetite, often resulting in
morbid obesity. There is currently no consensus as to
the cause for this particular symptom, although genetic
abnormalities in chromosome 15 disrupt the normal functioning
of the hypothalamus. Given that the hypothalamus regulates
many basic processes, including appetite, there may well
be a link. However, no organic defect of the hypothalamus
has been discovered on post mortem investigation.
Indications: Newborn with muscular hypotonia, children
with obesity, mental retardation, short stature, hygonadotropic
hypogonadism.
4. Miller Decker/Lis gene
5. Smith-Magenis
Smith-Magenis syndrome is a developmental disorder that
affects many parts of the body. The major features of
this condition include mild to moderate mental retardation,
delayed speech and language skills, distinctive facial
features, sleep disturbances, and behavioral problems.
Most people with Smith-Magenis syndrome have a broad,
square-shaped face with deep-set eyes, full cheeks, and
a prominent lower jaw. The middle of the face and the
bridge of the nose often appear flattened. The mouth tends
to turn downward with a full, outward-curving upper lip.
These facial differences can be subtle in early childhood,
but they usually become more distinctive in later childhood
and adulthood. Dental abnormalities are also common in
affected individuals.
Disrupted sleep patterns are characteristic of Smith-Magenis
syndrome, typically beginning early in life. Affected
people may be very sleepy during the day, but have trouble
falling asleep and awaken several times each night.
People with Smith-Magenis syndrome have affectionate,
engaging personalities, but most also have behavioral
problems. These include frequent temper tantrums and outbursts,
aggression, anxiety, impulsiveness, and difficulty paying
attention. Self-injury, including biting, hitting, head
banging, and skin picking, is very common. Repetitive
self-hugging is a behavioral trait that may be unique
to Smith-Magenis syndrome. People with this condition
also compulsively lick their fingers and flip pages of
books and magazines (a behavior known as "lick and
flip").
Other signs and symptoms of Smith-Magenis syndrome include
short stature, abnormal curvature of the spine (scoliosis),
reduced sensitivity to pain and temperature, and a hoarse
voice. Some people with this disorder have ear abnormalities
that lead to hearing loss. Affected individuals may have
eye abnormalities that cause nearsightedness (myopia)
and other vision problems. Although less common, heart
and kidney defects also have been reported in people with
Smith-Magenis syndrome.
Smith-Magenis syndrome is related to chromosome 17.
Mutations in the RAI1 gene cause Smith-Magenis syndrome.
6. Di George Syndrome-Tuple 1 probe
DiGeorge syndrome is a rare congenital (i.e. present at
birth) disease whose symptoms vary greatly between individuals
but commonly include a history of recurrent infection,
heart defects, and characteristic facial features.
DiGeorge syndrome is caused by a large deletion from chromosome
22, produced by an error in recombination at meiosis (the
process that creates germ cells and ensures genetic variation
in the offspring). This deletion means that several genes
from this region are not present in DiGeorge syndrome
patients. It appears that the variation in the symptoms
of the disease is related to the amount of genetic material
lost in the chromosomal deletion.
Although researchers now know that the DGS gene is required
for the normal development of the thymus and related glands,
counteracting the loss of DGS is difficult. Some effects,
for example the cardiac problems and some of the speech
impairments, can be treated either surgically or therapeutically,
but the loss of immune system T-cells (produced by the
thymus) is more challenging and requires further research
on recombination and immune function
Infants with DiGeorge syndrome often have distinct facial
features, including:
• Wide-set eyes
• Low-set ears, with a notched ear fold
• Small jaw
• A narrow, short groove in the upper lip
Other signs and symptoms of DiGeorge syndrome include:
• Cleft palate
• Recurrent infections, such as chronic runny nose or
multiple bouts of pneumonia, oral thrush (candidiasis),
diaper rash or diarrhea
• Cramp-like spasms of the baby's hands and fingers, or
twitches or spasms of the muscles in the baby's face,
throat or arms (tetany)
• Developmental delays, most often speech delay
• Slow mental development
• Lack of appetite
• Poor weight gain
• Failure to thrive
7. Di George Syndrome-N25 probe
DiGeorge syndrome is a rare congenital (i.e. present at
birth) disease whose symptoms vary greatly between individuals
but commonly include a history of recurrent infection,
heart defects, and characteristic facial features.
DiGeorge syndrome is caused by a large deletion from chromosome
22, produced by an error in recombination at meiosis (the
process that creates germ cells and ensures genetic variation
in the offspring). This deletion means that several genes
from this region are not present in DiGeorge syndrome
patients. It appears that the variation in the symptoms
of the disease is related to the amount of genetic material
lost in the chromosomal deletion.
Although researchers now know that the DGS gene is required
for the normal development of the thymus and related glands,
counteracting the loss of DGS is difficult. Some effects,
for example the cardiac problems and some of the speech
impairments, can be treated either surgically or therapeutically,
but the loss of immune system T-cells (produced by the
thymus) is more challenging and requires further research
on recombination and immune function.
Infants with DiGeorge syndrome often have distinct facial
features, including:
• Wide-set eyes
• Low-set ears, with a notched ear fold
• Small jaw
• A narrow, short groove in the upper lip
Other signs and symptoms of DiGeorge syndrome include:
• Cleft palate
• Recurrent infections, such as chronic runny nose or
multiple bouts of pneumonia, oral thrush (candidiasis),
diaper rash or diarrhea
• Cramp-like spasms of the baby's hands and fingers, or
twitches or spasms of the muscles in the baby's face,
throat or arms (tetany)
• Developmental delays, most often speech delay
• Slow mental development
• Lack of appetite
• Poor weight gain
• Failure to thrive
Leukemias
1. Bcr/Abl dual probe (CML):
Chronic myelogenous leukemia (CML) is an uncommon type
of cancer of the blood cells. It's considered chronic
leukemia because it usually progresses more slowly than
acute leukemia, sometimes over the course of years.
Any type of cancer can be frightening, of course. And
unfortunately, CML is not a solid tumor that can be surgically
removed. But the good news is that the prognosis for people
with chronic myelogenous leukemia may be improving because
of new medications to treat the condition. Although a
bone marrow transplant may still be an option, many people
with chronic myelogenous leukemia are able to manage their
condition long term with the use of chemotherapy-like
pills.
The presence of the Philadelphia chromosome (Ph') has
important diagnostic and prognostic implications in a
number of Haematological disorders. The abnormality is
characteristic of Chronic Myeloid Leukaemia (CML), found
in around 90% of cases but also represents a significant
abnormality in 30% of adult and 2 to 10% of childhood
Acute Lymphoblastic Leukaemia, (ALL) cases. This rearrangement
is also seen in rare cases of Acute Myelogenous Leukemia
(AML).
As a result of the Philadelphia translocation, t(9;22)(q34;q11),
The 3' sequences of the ABL(Abelson) proto-oncogene at
9q34 are joined to the 5' sequences of the BCR (Breakpoint
cluster region) gene at 22q11, giving rise to the BCR/ABL
hybrid or ‘fusion’ gene.
2. Translocation 8/21 probe (AML)
Acute myelogenous leukemia (AML) is a fast-growing cancer
of the blood and bone marrow. In AML, the bone marrow
makes many unformed cells called blasts. Blasts normally
develop into white blood cells that fight infection. However,
the blasts are abnormal in AML. They do not develop and
cannot fight infections. The bone marrow may also make
abnormal red blood cells and platelets. The number of
abnormal cells (or leukemia cells) grows quickly. They
crowd out the normal red blood cells, white blood cells
and platelets the body needs.
Acute leukemia with a particular chromosomal abnormality
often shows unique biological and clinical characteristics.
In these cases, the translocation (8;21)(q22;q22) (t(8;21))
is one of the most common karyotypic abnormalities in
acute myeloid leukemia (AML) and is closely associated
with the AML-M2 subtype. This type of AML has a high complete
remission (CR) rate with standard chemotherapy, and a
prolonged survival when sequential high-dose cytarabine
is administered. AML is frequently associated with a loss
of the sex chromosome Y in males and inactive X in females;
3.4% of the cases are variant translocations. However,
the influence of these variant translocations or additional
chromosomal abnormalities on the characteristics of t(8;21)
AML is still unclear.
3. Transloc. 15/17 probe (Ac Promyelocytic leukemia)
Chromosomal translocations leading to chimeric oncoproteins
are important in leukemogenesis. acute promyelocytic leukemia
(APL) is found to be associated with the t(15;17) translocation
which is identified for further analysis.
4. Breast cancer Her 2 gene amplification
Breast carcinoma is a common disease, with an estimated
183,000 new cases expected in the USA during 2000. Whereas
early stage patients have high likelihood of cure, only
20–40% of patients with metastatic breast carcinoma
respond to presently available chemotherapy. A need exists
to identify the underlying biological subsets of morphologically
similar carcinomas in order to develop customized therapies
for patients who require chemotherapy. The HER-2 receptor
tyrosine kinase is overexpressed in 15–30% of breast
carcinomas, and is associated with a worse prognosis stage-for-stage.
Humanized monoclonal antibody therapy appears to benefit
this subset of patients by improving their response rate
and survival following anthracycline- or taxane-based
chemotherapeutic regimens. Both HER-2 gene amplification
and protein overexpression correlate with clinical outcomes,
and screening for HER-2 gene amplification appears to
be the more informative test.
5. Small cell cancer of lung-EGFR mutation
Lung cancer is the leading cause of cancer-related mortality
in the United States. Non-small cell lung cancer (NSCLC)
accounts for >87% of all cases in lung cancer. More
than two-thirds of patients with NSCLC present with locally
advanced or systemic disease. Systemic chemotherapy has
been shown to prolong survival compared with best supportive
care in metastatic NSCLC. However, a plateau has been
reached with the use of cytotoxic chemotherapy in advanced
NSCLC. In the effort to develop more specific and effective
therapies, several molecular targets of potential importance
have been identified in NSCLC. In particular, the epidermal
growth factor receptor (EGFR) is commonly overexpressed
in NSCLC, and overexpression of EGFR has been associated
with poor prognosis.
6. Tasnlocation 8/14 (Burkitts, others)
Burkitt lymphoma (or "Burkitt's
tumor", or "Malignant lymphoma, Burkitt's type")
is a cancer of the lymphatic system (in particular, B
lymphocytes). Almost by definition, Burkitt lymphoma are
associated with c-myc gene translocation. The most common
variant is t(8;14)(q24;q32) while rarer variants include
t(2;8)(p12;q24) and t(8;22)(q24;q11). A three-way translocation,
t(8;14;18), has also been identified. It is curable.
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