Lec Notes: Introduction to Chromosomal Disorders

Prepared by: Roy P. Maribojoc MD MPH

Chromosomal anomaly or disorder is a result of a missing, extra, or irregular portion of

chromosomal DNA. It can be from an abnormal number of chromosomes or a structural defect
in one or more chromosomes.

Two main groups of Chromosomal Disorders

1. Numerical disorder
It occurs when an individual is missing either a chromosome from a pair (monosomy) or
has an extra or more than two chromosomes of a pair (trisomy, tetrasomy, etc.). In
humans an example of a condition caused by a numerical anomaly is Down Syndrome
also known as Trisomy 21 (an individual with Down Syndrome has three copies of
chromosome 21, rather than two). An example of monosomy is Turner Syndrome,
where the individual is born with only one sex chromosome, an X.
2. Structural disorder
When the chromosome's structure is altered, this can take several
forms: o Deletions: A portion of the chromosome is missing or deleted
o Duplications: A portion of the chromosome is duplicated, resulting in extra
genetic material.
o Inversions: A portion of the chromosome has broken off, turned upside down
and reattached, therefore the genetic material is inverted.
o Insertions: A portion of one chromosome has been deleted from its normal place
and inserted into another chromosome.
o Translocations: A portion of one chromosome is transferred to another
chromosome.
Examples of common chromosomal disorder in humans:
1. Cri Du Chat Syndrome
Cause: Cri Du Chat ("Cry of the cat") Syndrome is caused by missing portions of chromosome 5.
Primarily Affects: Both males and females, with females having a slightly higher frequency.
Symptoms: Symptoms of Cri Du Chat Syndrome include a high pitched cry in infants which is
similar to that of cats, mental retardation, small head, small jaw, low birth weight, slow growth,
abnormally shaped or low-set ears, slow or incomplete development of motor skills, wide set
eyes, webbing or fusing of fingers or toes, downward slanted eyes, low muscle tone, separated
abdominal muscles, etc.
Key Statistics:
Relatively rare genetic condition; estimated incidence of between around 1:25,000 to
1:50,000 births
2. Klinefelter Syndrome
Cause: Males with Klinefelter's Syndrome receive an extra X chromosome, thus giving them 47
rather than the normal 46 chromosomes (an extra sex chromosome).
Primarily Affects: Males. It is the most common sex chromosome disorder in males.
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Symptoms: Reduced fertility, neurophysiological impairments in terms of execution, smaller
testicles, gynecomastia (increased breast tissue), rounded body, etc.
Key Statistics:
• 47XXY, the most common of the sex chromosome variations, is said to occur in 1 out of 500
males.
• Thousands of 47XXY individuals in the United States alone. Many remain undiagnosed.

3. Turner Syndrome
Cause: Turner Syndrome is caused by the absence of entire X chromosome for
females. Primarily Affects: Females
Symptoms: Low-set ears, webbed neck, broad chest, non-working ovaries, hypothyroidism,
diabetes, vision problems, neuro/cognitive deficiency, congenital heart disease, etc. Key
Statistics:
• Turner Syndrome occurs in approximately 1 of every 2,000 female births and in as many as 10%
of all miscarriages.

4. Down Syndrome
Cause: In most cases, Down syndrome occurs when there is an extra copy of chromosome 21.
This form of Down syndrome is called Trisomy 21.
Primarily Affects: Equal frequency for males and females.
Symptoms: Symptoms of Down Syndrome include small ears, small mouth, upward slanting
eyes, flattened nose, decreased muscle tone at birth, wide hands, delayed mental
development, eye problems, hearing problems, hypothyroidism, hip problems, sleep apnea,
etc.
Key Statistics:
• There are more than 400,000 people living with Down syndrome in the United States. • Life
expectancy for people with Down syndrome has increased dramatically in recent decades - from
25 in 1983 to 60 today.
• The incidence of births of children with Down syndrome increases with the age of the mother.

5. Edwards Syndrome
Cause: Edwards Syndrome is also known as Trisomy 18. A person has a third copy of genetic
material from chromosome number 18, instead of usual two copies.
Primarily Affects: Appears to affect females three to four times more than males. Symptoms:
Low-set ears, mental deficiency, small head, small jaw, unusually shaped chest, low birth
weight, crossed legs (as a preferred position), congenital heart disease, kidney problems, cleft
or hole in iris, etc.
Key Statistics:
• Occurs in about 1:3000 live births.

• Small number of babies (<10%) live at least one year.

6. Patau Syndrome
 Cause: Patau Syndrome occurs when a person has three copies of genetic material from
chromosome 13, instead of the usual two copies. Thus, it is also known as Trisomy 13. Primarily
Affects: Females slightly more than males, or males and females equally.

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Symptoms: Cleft lip, decreased muscle tone, severe mental retardation, small eyes, small head,
undescended testicles, low-set ears, seizures, close-set eyes, skeletal abnormalities, clenched
hands, umbilical hernia, extra fingers or toes, etc.
Key Statistics:
• Occurs in approximately 1 in 10,000 live born infants.

7. Prader-Willi Syndrome
Cause: Seven genes are deleted or unexpressed on chromosome number
15 Primarily Affects: Equal frequency of males and females.
Symptoms: In utero: reduced movement, often-occurring abnormal fetal positions. At birth:
lethargy, feeding difficulties, hypotonia. In infancy: excessive sleeping, scoliosis. In childhood:
sleep disorders, excessive weight gain, speech delay, hyperphagia (over-eating). In
adolescence: delayed puberty, obesity, extreme flexibility. In adulthood: infertility, extreme
flexibility, hypotonia, decreased pubic hair. Adults with Prader-Willi Syndrome also often have
increased amount of central fat, narrow foreheads, almond-shaped eyes, and delayed motor
development.
Key Statistics:
• Prevalence estimates have ranged from 1:8,000 to 1:25,000 with the most likely figure being
1:15,000.

8. Angelman Syndrome
Cause: Angelman Syndrome is caused by the deletion of genetic material on maternally
inherited chromosome 15. It is often counted as a "sister disorder" to Prader-Willi Syndrome
due top to occurrence in same genetic area.
Primarily Affects: Equal frequency for males and females.
Symptoms: Angelman Syndrome is a neuro-genetic disorder. Symptoms include seizures, jerky
movements, speech impairments, small head size, hyperactivity, motor difficulties, etc. Key
Statistics:
• Prevalence of Angelman's Syndrome among children and young adults is between 1/10,000 and
1/20,000

9. Fragile X Syndrome
Cause: In Fragile X Syndrome, expansion of a single trinucleotide gene sequence (CGG) on the X
chromosome occurs. This results in a failure to express the protein coded by the FMR1 gene.
Primarily Affects: Males more severely than females.
Researchers: Dr. Randi J. Hagerman, Dr. Paul Hagerman.
Symptoms: Mental retardation, tendency to avoid eye contact, speech and language delays,
hyperactive/impulsive behavior, long face, large body size, flat feet, soft skin, oversized testes
in males who have reached puberty, large forehead or ears, prominent jaw, etc. Key Statistics:
• Fragile X syndrome is the most common inherited cause of mental impairment. The syndrome
occurs in approximately 1 in 3600 males and 1 in 4000 to 6000 females.