Examples of Genetic Disorders

Edward Syndrome

Other name: Trisomy 18

Symptoms: growth deficiency, small head (microcephaly), small jaw/mouth (micrognathia), clenched fists with overlapping fingers, mental retardation, developmental delays, heart defects, underdeveloped lungs, and other skeletal and organ anomalies.

Mortality Rate: 95% of fetuses with Trisomy 18 will not survive to birth. Of those who are live born, only 5-10% will live to be one year old.

Prevalence: 1 in 3000-8000 live births. 80% of people with this condition are female.

Cause: Extra chromosome 18 in each cell (3 copies instead of 2). Trisomy 18 is the second most common trisomy seen in live born individuals. The extra chromosome is likely due to nondisjunction during meiosis.

Link: Trisomy 18 Foundation

Link: SOFT (Support Organization for Trisomy 18, 13, and Related Disorders)

Down Syndrome

Other name: Trisomy 21

Symptoms: People with Down Syndrome have similar facial features including a flattened facial profile, upward slanting eyes, small over-folded ears, and a protruding tongue when they are young. They can also have low muscle tone, a shorter than typical neck, a single crease across the palm of the hand, heart defects, and varying levels of intellectual disability.

Mortality: Many pregnancies with Trisomy 21 (Down Syndrome) will miscarry before birth. However, babies that are live born generally have good survival depending on the severity of heart defects and other medical concerns. Due to research and improved medical care, the life expectancy has increased in recent years. Approximately 80% of children with Down Syndrome will survive to age 10, and 50% will survive to age 50. With good medical care and therapy many people with Down Syndrome will graduate high school and hold a job in the community.

Prevalence: 1 in every 800-1000 live births. Trisomy 21 is the most common trisomy seen in live born individuals.

Cause: Extra copy of chromosome 21 in each cell. The extra chromosome is most likely due to nondisjunction during meiosis. A less common cause of Down Syndrome is a robertsonian translocation (see below).

Link: National Association for Down Syndrome

Robertsonian Translocation

Cause: This is a type of translocation in which two chromosomes break at their centromere and the long pieces of each chromosome join together to produce one structure containing 2 chromosomes. The chromosomes that usually undergo this type of translocation are those whose centromeres are near the end of the chromosome (chromosome numbers 13, 14, 15, 21, and 22). The term acrocentric is used to describe these chromosomes with centromeres near one end. The “short arm” of the chromosome that breaks off at the centromere is lost because it is not stable and does not contain essential information. This type of translocation can occur in either a balanced or an unbalanced form. Symptoms: People who have a balanced form of the translocation show no symptoms. However, their children have a risk of inheriting an unbalanced form of the translocation and having an extra or missing chromosome. For example a child who inherits a chromosome from one parent containing two long arms of chromosome 21 fused together and another single chromosome 21 from the other parent will then have essentially 3 copies of chromosome 21 and have Down Syndrome features.

Mortality: Often fetuses that inherit an unbalanced form will miscarry as the extra or missing information will not be viable with life. The most common live born unbalanced form is 3 copies of chromosome 21 (Down Syndrome).

Prevalence: The prevalence of balanced robertsonian translocations is about 1 in 1000. The two most common robertsonian translocations are between chromosomes 13 and 14 (makes up about 85%) and 14 and 21 (makes up about 10%). The 14;21 translocation is the most clinically significant because it the unbalanced form can cause Down Syndrome.

Link: Robertsonian translocation resource page by Washington State University

Cri-du-chat Syndrome

Other name: 5p- syndrome or 5p deletion syndrome

Symptoms: Abnormal larynx and epiglottis which causes a distinct sounding cry. The name literally means “cry of the cat.” The cry becomes less distinct after the age of 2. Other symptoms include a low birth rate, poor muscle tone, mental retardation, small head (microcephaly). Characteristic facial features at birth include a large nasal bridge, round face, wide-spaced eyes, low-set ears, and a down-turned mouth. As the child gets older the facial features change and a long, narrow face is more commonly observed.

Mortality: Survival to adulthood has been observed but is not common.

Prevalence: 1 out of 50,000 live births

Cause: A deletion of genetic material on the short arm of chromosome number 5.

Link: 5P- Society

Patau Syndrome

Other name: Trisomy 13

Symptoms: Severe mental retardation, multiple physical differences, and many medical problems. Common features include : heart defects, small heads (microcephaly), cleft lip and/or palate, small eyes that are close together, extra fingers (polydactyly), skeletal abnormalities, low muscle tone, skeletal abnormalities, and holoprosencephaly (only one hemisphere of the brain).

Mortality: Only about 5% of Trisomy 13 fetuses will be live born. Of those that make it to birth, about 95% will pass away during the first year. The average survival time for those that are live born is about 7 days.

Prevalence: 1 out of 10,000

Cause: 3 copies of chromosome 13 in each cell, typically caused by nondisjunction during meiosis.

Link: SOFT (Support Organization for Trisomy 18, 13, and Related Disorders)

Klinefelter Syndrome

Other name: XXY

Symptoms: People with a XXY karyotype are males with an extra X chromosome. These individuals are typically tall, with long arms and legs, have hypogonadism (small testes), decreased body hair, low muscle tone, and cannot reproduce. About 1/3 of these men will develop breast tissue (gynecomastia) and have an increased risk for breast cancer. There is also a risk for learning disabilities and social problems.

Mortality: No decrease in lifespan

Prevalence: 1 out of 500-1000 male births

Cause: Male with an extra X chromosome. The extra X typically is due to nondisjunction during meiosis.

Link: American Association for Klinefelter Syndrome Information and Support

Chronic Myelogenous Leukemia (CML)

Definition: CML is a cancer of the bone marrow caused by rapid growth of blood-forming cells. This syndrome makes up 7-20% of all leukemia cases.

Symptoms: Symptoms are usually vague and non-specific, including fatigue, weakness, fever, swollen spleen, bleeding, and bruising. Lab tests often show an increase in white blood cells and decrease in red blood cells and platelets.

Prevalence: 1-2 out of 100,000

Cause: A chromosome reciprocal translocation occurs between chromosomes 9 and 22. This essentially means that a large piece of chromosome 22 and a small piece of chromosome 9 have broken off and switched places. The result is called the “philadelphia chromosome.” Although no information is lost or added during the translocation, one of the genes moved from chromosome 9 to chromosome 22 is the ABL proto-oncogene
It is important to note that this is not a translocation you are born with, but rather it is one that can develop overtime in somatic cells (non-reproductive cells) such as bone marrow cells.

Link: The Leukemia and Lymphoma Society

Triple X Syndrome

Other name: Trisomy X

Symptoms: Usually no major physical differences. Sometimes these women cannot reproduce, have irregular menstrual cycles, and are at risk for mild learning disabilities.

Mortality: No decrease in lifespan

Prevalence: 1 out of 1000 females

Cause: 3 copies of the X chromosome in each cell typically due to nondisjuction during meiosis.

Link: Information from Genetics Home Reference

22q11.2 Deletion Syndrome

Other name: Velocardiofacial Syndrome (VCFS); DiGeorge Syndrome

Symptoms: Individuals with this deletion typically have heart defects, distinctive facial appearance, underdeveloped or absent thymus and parathyroid glands, and cleft palate and/or cleft lip. The immune system T-cells are made in the thymus, so these patients commonly have weak immune systems. These patients also commonly have low calcium levels because it is the parathyroid gland that regulates body calcium levels. Most will have some level of learning disability.

Mortality: Usually live into adulthood unless there are severe heart or immune system problems.

Prevalence: 1 out of 4000 live births

Cause: A small deletion on the long arm of chromosome 22. In more than 90% of cases the deletion is a new mutation meaning that the patient is the first person in the family to have the deletion and it was not inherited.

Link: 22q11.2 Deletion Syndrome Foundation

XYY Karyotype

Symptoms: Usually none physical differences are caused by an extra Y chromosome. Sometimes these boys/men are taller than average and have an increased risk of learning disabilities and minor behavior problems.

Mortality: No decrease in lifespan.

Prevalence: 1 out of 1000 males

Cause: Males that have an extra Y chromosome in each cell.

Link: Information from the Genetics Home Reference

Fragile X Syndrome

Symptoms: Range of learning disorders, distinctive facial appearance with large ears and a long face, prominent jaws, behavioral challenges, as well as speech and language problems.

Prevalence: 1 out of 4,000 males; 1 out of 8,000 females

Cause: A mutation in the FMR1 gene located on the X chromosome. Within this gene, there is a region containing the DNA sequence “CGG” repeated multiple times (called a tri-nucleotide repeat). Normally the sequence is repeated no more than 55 times in the gene. However, Fragile X Syndrome occurs when a person has more than 200 “CGG” repeats in the FMR1 gene. This gene normally functions to make a protein needed for brain development.

Inheritance: Fragile X Syndrome is inherited in an X-linked pattern. Males only have only one X chromosome and therefore only have one copy of the FMR1 gene. A mutation (more than 200 repeats) in their one copy causes Fragile X Syndrome. Females have two X chromosomes and therefore have two copies of the FMR1 gene. If a female has a mutation on one of her copies, the other unchanged copy can compensate. Females with a change in one of their FMR1 genes are considered “carriers” for Fragile X Syndrome. Some carrier females can show symptoms of the syndrome but are typically more mildly affected than males. Another unique aspect to the inheritance of this disorder is the fact that the number of repeats can increase from one generation to the next particularly when it is passed through the mother. This process of repeat expansion which often leads to a more severe disease is called anticipation.
A person who has more than 55 repeats, but less than 200, is considered a “pre-mutation carrier.” These individuals do not have Fragile X Syndrome themselves but are at risk of having children affected with the disorder since the number of repeats could expand in the next generation. These pre-mutation carriers are themselves also at risk for some other physical problems such as pre-mature ovarian failure in women and tremor/ataxia syndrome in men.

Mortality: No decrease in lifespan

Link: National Fragile X Foundation

Link: Information from Genetics Home Reference

Turner Syndrome

Other name: Monosomy X

Symptoms: People with Turner Syndrome are females and typically have short stature, a webbed neck, heart defects, kidney problems, swelling of the hands and feet, and characteristic facial features. They also typically have loss of ovarian function and do not undergo puberty. Therefore it is uncommon for these women to have children of their own.

Mortality: Life expectancy depends on the presence of any serious medical conditions (ex. heart defects). For most the lifespan is typical.

Prevalence: 1 out of 2500 girls

Cause: Females with only one X chromosome. This typically occurs due to nondisjunction during meiosis.

Link: Turner Syndrome Society of the United States

3 inversion/Normal phenotype

Other name: 3p25q21

Symptoms: None

Cause: A small inversion of the genetic material on chromosome 3. An inversion occurs when a chromosome breaks in two places and the information between the two breakpoints reverses directions before rejoining. This is considered a pericentric inversion because the inversion includes the centromere of chromosome 3, with the breakpoints on either side. No genetic information is lost during the inversion; simply the order of the information is changed. Inversions can occur at any point along a chromosome and the severity of the symptoms associated with it depends on the genes involved and the size of the inversion. The name 3p25q21 tells you where on the chromosome the inversion has occurred. In this case it is chromosome number 3 and the inversion spans between the short arm (p) at location 25 and the long arm (q) at location 21.

9 inversion/Normal phenotype

Other name: 9p11q12

Symptoms: None

Cause: A small inversion in the DNA on chromosome 9 and the most commonly observed inversion in humans. An inversion occurs when a chromosome breaks in two places and the information between the two breakpoints reverses directions before rejoining. This is considered a pericentric inversion because the inversion includes the centromere of chromosome 9, with the breakpoints on either side. No genetic information is lost during the inversion; simply the order of the information is changed. Inversions can occur at any point along a chromosome and the severity of the symptoms associated with it depends on the genes involved and the size of the inversion. The name 9p11q12 tells you where on the chromosome the inversion has occurred. In this case it is chromosome number 9 and the inversion spans between the short arm (p) at location 11 and the long arm (q) at location 12.