CYTO311: CYTOGENETICS

TOPIC: CHROMOSOMAL DISORDERS

1ST SEMESTER | S.Y 2024-2025
LECTURER: Ma’am Pamela Sengson-Sevilla, RMT, ASCPi
TOPIC TRISOMY 21: DOWN SYNDROME
SUBTOPIC • 47, +21
SUB SUBTOPIC • Found in 1/700
• Only human autosomal trisomy wherein the
individual survives longer that 1 year
CHROMOSOMAL DISORDERS • Discovered in 1866 by Langdon Down
- Formerly tagged as ‘mongoloid’ or
• Focused on specific conditions or disorders brought
‘mongoloidism’
about by the chromosomal aberrations • Groups concerned here are Group G
AUTOSOMAL MONOSOMY • According to Down Syndrome Association of the
Philippines, Inc. (DSAPI), more than 100,000 Filipino
• The most common example of aneuploidy wherein an families are living with a person with Down syndrome
organism has a chromosome number other than an • Leading cause of mental retardation and heart
exact multiple of haploid set are cases in which a single defects in US
chromosome is either added to or loss from a normal • Wide flat skulls, skin folds in the corner of the eyes,
diploid set. spots on the irises, and thick, furrowed tongues
• In this case, we have a loss of one chromosome, • 40% congenital heart defects
produces a diploid number minus one [2n-1] • In karyotyping, there are 3 on the chromosome 21
[trisomy 21]
• Lethal condition
• Chromosome 14 is involved also on Down syndrome.
- Single copy can contain only the recessive gene, and
When this chromosome is involved, it is called the
that copy may be insufficient to provide adequate
Translocation Down Syndrome
function to sustain the organism → - Robertsonian Translocation: translocation of
Haploinsufficiency chromosome 14 and chromosome 21
o Haploinsufficiency – this may be because of - Robertsonian Translocation can happen in one of
just a single copy [recessive gene that has the two ways:
insufficient or inadequate function to 1. Extra genes in the egg or sperm
sustain the organism] 2. By chance or random
• Aneuploidy during gamete formation produces equal • Chromosome 21 is often tagged as “non-hereditary”
numbers of monosomic and trisomic gametes and since it is associated in random causes
embryos

AUTOSOMAL TRISOMY
• 2n + 1
• Most are lethal
• Varies by chromosome
• 50% of cases of chromosomal abnormalities that causes
fetal death are because of autosomal trisomy
• Examples:
- Trisomy 13: Patau syndrome (47, +13)
- Trisomy 18: Edwards syndrome (47, +18)
- Trisomy 21: Down Syndrome (47, +21)
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 • Shows the relationship between the incidence of • Affected individuals are male with low fertility and
Down Syndrome births and maternal age may have mental dysfunction
• It states that there is an dramatic increase in the • 60% due to maternal nondisjunction
number of down syndrome birth as the maternal age • Features:
of the mother increases - Generally tall
- Mas increase ‘yung births ng down syndrome in - Long arms and legs
ages of 35 years old [in other references] - Large hands and feet
- Child bearing age nowadays: between 30 and 40 - External genitalia and internal ducts, but their
TRISOMY 18: EDWARDS SYNDROME testes are rudimentary [fail to produce sperm]
• 47, +18 • Since they have an additional X chromosome, the
• 1/11,000 births feminine sexual development is not entirely
• Can survive up to term; less than 1 year survival time suppressed.
• Average survival time is 2-4 months • They have:
• Affected infants small at birth grow slowly and are - Enlarged breasts [gynecomastia]
mentally retarded [intellectually disabled] - Rounded hips
• Malformation of heart, hands, and feet - Intersexuality
TRISOMY 13: PATAU SYNDROME JACOB’S SYNDROME
• 47, +13 • 47, XYY
• 1/15,000 births • 1/1000 births
• Lethal; mean survival time is 1 month • Discovered in 1965 by Patricia Jacobs
• Facial malformations [cleft palate or cleft lip], eye - Went to Scottish Prison
defects, extra fingers or toes, and large protruding - 9 out of 315 prisoners of males have this kind of
heels syndrome
• Severe malformations of brain, nervous system, and - 7 out of those 9 have subnormal intelligence and
heart all have suffered from personality disorders
TURNER’S SYNDROME • Above average in height
• 45, X • No established link with possible antisocial behavior
• 1/10,000 births • Boys with XYY syndrome may have some or all of
• Affected individuals: Females; these physical symptoms to some degree:
• Short stature [under 5 ft], wide chest; rudimentary - Taller than average height
ovaries [poorly developed or non-functional]; and - Low muscle tone, or muscle weakness
[hypotonia]
abnormal sexual development
- Very curved pinky finger
• individuals having this syndrome does not have metal
- Widely spaced eyes
dysfunction or minimal dysfunction
- Cystic acne during adolescence [most serious
• puffiness of hands and feet
type of acne; causes painful fluid-filled bumps
• abnormalities of the aorta
across the surface]
• Single X chromosome: two X chromosomes are
TRISOMY X [TRIPLO-X]
required for normal female sexual development
• 47, XXX
• Features:
• 1/1000 births
- Short stature [under 5 ft], cognitive impairment,
• Above average in height
difficulty in learning new things and
concentrating in decisions • No noticeable effects or have only mild symptoms
- Skinfolds are evident on the back of their neck • Girls with XXX syndrome may have some or all of
- Underdeveloped breasts these symptoms to some degree:
- Chest is like shield-like [very broad] - Delayed development of speech and language
KLINFELTER SYNDROME skills, as well as motor skills
- Learning disabilities
• 47, XXY
- Behavioral problems
• 1/1000 births
- Psychological problems
• Features do not develop until after puberty
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 ANGELMAN SYNDROME
• Rare genetic and neurological disorder characterized
AMTERNAL AGE EFFECTS by severe developmental delay and learning
• Trisomy 21 disabilities;
• Trisomy 13 • 15q11.2
- Maternal segment is deleted; paternal segment
• Trisomy 18
remains undeleted
• XXX and XXY
• Developmental delays, including no crawling or
• The risk for aneuploidy increases with maternal age babbling at 6 to 12 months
primarily owing to meiotic nondisjunction errors • Intellectual disability
associated with reduced recombination or crossing over • No speech or minimal speech
prior to the first meiotic division • Difficulty walking, moving, or balancing well
• For trisomy 21, it is more linked to random events • Frequent smiling and laughter
• Happy, excitable personality
• Trouble going to sleep and staying asleep
CRI DU CHAT SYNDROME 1P36 DELETION SYNDROME
• Cri du chat syndrome is a rare genetic disorder due to [MONOSOMY 1P36]
chromosome deletion on chromosome 5. • Individuals having this condition may have temper
- 5p15.2 tantrums, tendency of biting themselves, they usually
- Missing portion is small, it is better to refer it as have small head, deep set eyes with straight
“segmental deletion” eyebrows, and the middle of their face appears
• First reported by Jerome LeJeune in 1963, wherein he sunken [termed as mid-face hypoplasia], their nose is
describes the crying of the baby as eerie, similar to often broad and flat
the meowing of the cat • A congenital genetic disorder characterized by
- This feature may be linked to underdevelopment moderate to severe intellectual disability, delayed
of glottis and larynx which is typical to this growth, hypotonia, seizures, limited speech ability,
syndrome malformations, hearing and vision impairment, and
- Other features may include anatomical distinct facial features
malformations, including but not limited to, • 1 in every 5,000 to 10,000 births
gastrointestinal complication, cardiac
complications
• Its name is a French term (“cat-cry” or “cry of the PHILADELPHIA CHROMOSOME
cat”) referring to the characteristic cat-like cry of • Chromosomal abnormalities can also occur in cancer
affected children cells or individuals that has normal genetics
PRADER WILLI SYNDROME
• Example: leukemic white blood cell from patient with
• Prader-Willi syndrome is a rare genetic disorder that
chronic myeloid leukemia [has specific bcrabl gene]
results in a number of physical, mental, and
behavioral problems • A translocation mutation commonly associated with
• The paternal segment is deleted; maternal segment chronic myelogenous leukemia and less often with
remains undeleted acute lymphoblastic leukemia
- Linked to this region → Chromosome 15q11.2
• Constant sense of hunger – starts to 2 years old
• Hyperphagia
• Obesity
• Underdeveloped genitals
• Behavioral problems
• Hypopigmentation
• Cognitive impairment

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• Abelson gene in 9q34 → breakpoint is the cluster region
of the chromosome 22
• t (9,22) (q34; q11.2)
• Normally, the ABL gene is a protein kinase that acts
within a signal transduction pathway [transfers growth
factors signal to the environment and nucleus]
• Since there is a translocation, new gene will code for
another protein [abnormal protein: bcr-abl → abnormal
signal transduction molecule which stimulate the cells
to accumulate without signals
• From the normal abl protein, wherein it is a kinase that
acts on a signal transduction to the nucleus

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