CHROMOSOME ABNORMALITIES

By Rui Ting Zheng

Rica Jane P. Laysa

BACKGROUND As a rule, the cells of all organisms contain a

constant number of chromosomes that have maintained a constant structure throughout development.

Major exceptions to this rule include gametes produced by meiosis (egg and sperm cells contain a reduced number of chromosomes), and cell types in which a change in chromosome number or structure is necessary for function (immune cells generate a large antibody repertoire using chromosome rearrangement). These exceptions occur only in specialized cell types, and reflect changes made to the original chromosomal content of an individual organism which is set at fertilization.

Environmental Risk Factors

Radiation

Smoking

Fertility drugs

Alcohol consumption

Oral contraceptive

There are 2 basic types of Chromosome Abnormalities

1. change in the structure of chromosomes (structural abnormality)

2. change in the number of chromosomes (numerical abnormality)

Numerical and Structural Abnormality are not mutually exclusive, they may be present at the same time.

Numerical Abnormality Euploidy

  An exact multiple of the haploid chromosome

complement. Diploid (2N) Ployploid: Triploid (3N)

Tetraploid (4N)

Pentaploid (5N)

Autoploid

Alloploid

Aneuploidy

The variation involves addition or deletion of one or more chromosomes, but not in the complete set.

Monosomy (2N-1) Disomy (2n) Trisomy (2N+1) Tetrasomy (2N+2) Pentasomy (2N+3)

Sex Chromosome Aneuploidies MALE

Klinefelter Syndrome ( 47, XXY )

Human males who have extra X chromosome

It occurs in about 1 out of 500 - 1,000 newborn boys. Characteristics :

- Small testicles and penis

- Abnormal body proportions (long legs, short trunk, shoulder equal to hip size)

- Abnormally large breasts (gynecomastia)

- Infertility

- Sexual problems

- Less than normal amount of pubic, armpit, and facial hair

- Tall height

Jacobs Syndrome ( 47, XYY )

Human males who have extra X-chromosome. It occurs in 1 in 1000 male births.

Characteristics :

- Male criminals

- Antisocial / Uncontrolled temper

- Tall and Thin

- Have acne

- Speech and Reading problems.

- Learning problems at school

- Delayed emotional maturity

FEMALE Metafemale Syndrome ( 47, XXX )

Human woman who has an extra chromosome.

It affects one in every 1500 female births. Characteristics :

- bionic woman

- taller and thiner

- normal in barr bodies

- Behavioral problems

- Clumsiness and poor co-ordination

- Wide-set eyes

- Reduced muscle tone

- Ovarian failure

Turner Syndrome ( 45, X )

Human woman who lack one sex chromosome.

It occurs in 1 out of 2000-5000 females. Characteristics : - Short stature

- Webbed neck

- Lymphedema (swelling) of the hands and feet

- Low-set ears

- Low hairline

- non-working ovaries

Structural Abnormality1. Deletions – “ delete”

- Loss of the segment of chromosome

(shorter)

- Breaks of the chromosome caused by

hazards.

1.1 Terminal Deletion - a deletion that occurs towards the end of a chromosome.

1.2 Intercalary Deletion - a deletion that occurs from the interior of a chromosome.

Examples of large-scale chromosomal deletions: A, terminal; B, Intercalary.

2. Duplications - A portion of the chromosome is duplicated, resulting in extra genetic material.

2.1 Tandem Duplication

The duplicating segment gets incorporated next to normal corresponding segment. e.g., ABC · DEDEFG

2.2 Reverse Tandem Duplication

The duplicating segment gets incorporated next to normal corresponding segment.

e.g., ABCCBDEF

2.3 Displaced Homobrachial Duplication

e.g., ABC · DEFDE

2.4 Displaced Heterobrachial Duplication

e.g., ABCDED · EF

3. Inversion – rotation of the segment of thechromosome to a full 180°.

3.1 Paracentric

Does not involed the centromere

e.g., ABC · EDF

3.2 Pericentric

Involed the centromere

e.g., ED · CBAF

4. Translocation – exchange of the genetic marterial between a non-homozygous.

4.1 Reciprocal Translocation

e.g., ABC · DEF ABC · 4 5 F

1 2 3 · 4 5 6 1 2 3 · D E 6

There are two types of reciprocal translocations :

Balanced - in an even exchange of material with no genetic information extra or missing, and ideally full functionality and unbalanced.

  Unbalanced - where the exchange of chromosome material is unequal resulting in extra or missing genes.

4.2 Non-reciprocal ( Insertion )The insertion of a segment from one chromosome into another non- homologous chromosome.

e.g., ABC · 4 5DEF

1 2 3 · 6

AUTOSAMAL ABBERATIONS Cri du chat

Also known as chromosome 5p deletion syndrome is a rare genetic disorder due to a missing part of chromosome 5.

The condition affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio.

Characteristics :

- cat-like cry of affected infant.

- excessive drooling.

- feeding problems because of difficulty swallowing and

sucking.

- low birth weight and poor growth.

- severe cognitive, speech, and motor delays.

- behavioral problems such as hyperactivity, aggression,

tantrums, and repetitive movements.

- unusual facial features which may change over time.

- constipation.

Down syndrome

Also known as trisomy 21, is a chromosomal

condition caused by the presence of all or part of an

extra 21st chromosome. Characteristics :

- oblique eyes feature - mental retardation

- stunted growth

- atypical fingerprints

- separation of the abdominal muscles

- flexible ligaments

- Hypotonia

- brachycephaly

- smaller genitalia

- shortened extremities

- oval palate

- low-set and rounded ear

Wolf–Hirschhorn syndrome Also known as chromosome deletion Dillan 4p syndrome.

It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosom.

Characteristics :

- short philtrum,

microcephaly, micrognathia,

prominent glabella

ocular hypertelorism

dysplastic ears,

periauricular tags.

- growth and mental retardation

- muscle hypotonia

- seizures

- congenital heart defects.

Jacobsen syndrome

Also known as 11q deletion disorder, is a rare congenital disorder resulting from deletion of a terminal region of chromosome 11 that includes band 11q24.1.

Characteristics :

- bleeding disorder

- heart defects

- Mild to severe intellectual disabilities

- Low-platelets (thrombocytopenia)

- Facial/skeletal (dysplasia)

- Wide-set eyes caused by trigonocephaly

- Folding of the skin near the eye (epicanthus)

- Short, upturned nose (anteverted nostrils)

- Thin lips that curve inward

- Displaced receding chin (retrognathia)

- Low-set, misshapen ears

Pallister–Killian syndrome

Also tetrasomy 12p mosaicism or Pallister mosaic aneuploidy syndrome, it occurs due to the presence of the anomalous extra isochromosome 12p.

Characteristics : - hypotonia

- hypopigmentation, hyperpigmentation

- developmental disability

- epilepsy

- foreheads

- sparse hair on the temple

- a wide space between the eyes

- Visual impairments and deafness

Patau syndrome

Also known as trisomy 13 and trisomy D, is a chromosomal abnormality, a syndrome in which a patient has additional chromosome 13 due to a nondisjunction of chromosomes during meiosis.

Characteristics : - Polydactyly (extra digits)

- Microcephaly

- Low-set ears

- Overlapping of fingers over thumb

- Polydactyly (extra digits)

- Cleft palate

- Abnormal genitalia

- Omphalocele (abdominal defect)

Cat eye syndrome A rare condition caused by the short arm (p) and a small section of

the long arm (q) of human Chromosome 22 being present three (trisomic) or four times (tetrasomic) instead of the usual two times.

Characteristics : - Anal atresia (abnormal obstruction of the anus)

- Unilateral or bilateral iris coloboma (absence of tissue from the colored part of the eyes)

- Palpebral fissures (downward slanting openings between the upper and lower eyelids)

- Preauricular pits/tags (small depressions/growths of skin on the outer ears)

- Cardiac defects (such as TAPVR)

- Kidney problems (missing, extra, or underdeveloped kidneys)

- Short stature

- Scoliosis/Skeletal problems

- Mental retardation

- Hernias

- Rarer malformations can affect almost any organ

Edwards syndrome Also known as Trisomy 18 (T18) or Trisomy E) is

a genetic disorder caused by the presence of all or part of an extra18th chromosome.

Characteristics :

- kidney malformations

- structural heart defects

- upturned nose

- low-set,malformed ears

- intestines protruding outside the body (omphalocele)

- small head (microcephaly) accompanied by a prominent back portion of the head (occiput)

- clenched hands;underdeveloped thumbs and or nails

Isodicentric 15 Also called idic(15), partial tetrasomy 15q, or inverted

duplication 15 (inv dup 15), is a chromosome abnormality in which a child is born with extra genetic material from chromosome 15.

Characteristics : - have delays in language development and motor skills

- low muscle tone (hypotonia)

- seizures

- short stature

- mental retardation

- epicanthal folds (skin folds at the inner corners of the eyes)

- a flattened nasal bridge, button nose

- a high arched palate (roof of the mouth)

- have features of autism, such as problems with communication, social interactions, and repetitive and stereotyped behaviors

THE END