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48,XXXY Syndrome

Table of Contents

48,XXXY Syndrome

XXXY syndrome; XXXY males; Klinefelter's syndrome (XXXY)

48,XXXY syndrome is a type of chromosome abnormality characterized by the presence of 2 extra X chromosomes in males. It is sometimes referred to as a variant of Klinefelter syndrome, but differs from Klinefelter syndrome in many ways and is more severe.

DNA Helix

Image by National Human Genome Research Institute (NHGRI)

What Is

47,XXY

Image by No machine-readable author provided. The cat~commonswiki assumed (based on copyright claims)./Wikimedia

47,XXY

47,XXY en:karyotype with two X chromosomes and one Y chromosome in the lower right. This is known as en:Klinefelter Syndrome and XXY syndrome. Typically, a human male has one X and one Y chromosome and a female has two X chromosomes.

Image by No machine-readable author provided. The cat~commonswiki assumed (based on copyright claims)./Wikimedia

What Is 48,XXXY Syndrome?

48,XXXY syndrome is a chromosomal condition in boys and men that causes intellectual disability, developmental delays, physical differences, and an inability to father biological children (infertility). Its signs and symptoms vary among affected individuals.

Most boys and men with 48,XXXY syndrome have mild intellectual disability with learning difficulties. Speech and language development is particularly affected. Most affected boys and men can understand what other people say more easily than they themselves can speak. The problems with speech and communication can contribute to behavioral issues, including irritability and outbursts or temper tantrums. Boys and men with 48,XXXY syndrome tend to have anxiety, a short attention span, and impaired social skills.

48,XXXY syndrome is also associated with weak muscle tone (hypotonia) and problems with coordination that delay the development of motor skills, such as sitting, standing, and walking. Affected boys and men tend to be taller than their peers, with an average adult height of over 6 feet.

Other physical differences associated with 48,XXXY syndrome include abnormal fusion of certain bones in the forearm (radioulnar synostosis), an unusually large range of joint movement (hyperextensibility), elbow abnormalities, curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus). Affected individuals may have distinctive facial features, including widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point upward (upslanting palpebral fissures), and skin folds covering the inner corner of the eyes (epicanthal folds). However, some boys and men with 48,XXXY syndrome do not have these differences in their facial features.

48,XXXY syndrome disrupts male sexual development. The penis is shorter than usual, and the testes may be undescended, which means they are abnormally located inside the pelvis or abdomen. The testes are small and do not produce enough testosterone, which is the hormone that directs male sexual development. The shortage of testosterone often leads to incomplete puberty. Starting in adolescence, affected boys and men may have sparse body hair, and some experience breast enlargement (gynecomastia). Their testes typically do not produce sperm, so most men with this condition are infertile.

Source: MedlinePlus Genetics

Is It Common?

How common?

Image by Gerd Altmann

How common?

Image by Gerd Altmann

How Common Is 48,XXXY Syndrome?

48,XXXY syndrome affects between 1 in 17,000 and 1 in 50,000 newborn boys. It is a relatively uncommon sex chromosome disorder, which is a group of conditions caused by changes in the number of sex chromosomes (the X chromosome and the Y chromosome).

Source: MedlinePlus Genetics

Causes

Pregnancy and the X Chromosome

Image by Pregnancy and the X Chromosome

Pregnancy and the X Chromosome

TheVisualMD

Image by Pregnancy and the X Chromosome

What Causes 48,XXXY Syndrome?

48,XXXY syndrome is a sex chromosome disorder in boys and men that results from having two extra X chromosomes in each cell. People typically have 46 chromosomes in each cell, two of which are the sex chromosomes. Females have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY). Boys and men with 48,XXXY syndrome have the usual single Y chromosome, but they have three copies of the X chromosome, for a total of 48 chromosomes in each cell.

Boys and men with 48,XXXY syndrome have extra copies of multiple genes on the X chromosome. The activity of these extra genes affects many aspects of development, including sexual development before birth and at puberty. Researchers are working to determine which genes contribute to the specific developmental and physical differences that occur with 48,XXXY syndrome.

48,XXXY syndrome is sometimes described as a variant of another sex chromosome disorder called Klinefelter syndrome. Boys and men with Klinefelter syndrome have one extra copy of the X chromosome, for a total of 47 chromosomes in each cell (47,XXY). Like 48,XXXY syndrome, Klinefelter syndrome affects male sexual development and can be associated with learning disabilities and problems with speech and language development. However, the features of 48,XXXY syndrome tend to be more severe than those of Klinefelter syndrome and affect more parts of the body. As doctors and researchers have learned more about the differences between these sex chromosome disorders, they have started to consider them as separate conditions.

Source: MedlinePlus Genetics

Inheritance

Human Genome - Infant and DNA

Image by TheVisualMD

Human Genome - Infant and DNA

Human Genome - Inheritance

Image by TheVisualMD

How Is 48,XXXY Syndrome Inherited?

This condition is not inherited; it occurs as a random event during the formation of reproductive cells (eggs or sperm) in one of an affected person's parents. During cell division, an error called nondisjunction prevents X chromosomes from being distributed normally among reproductive cells as they form. Typically, as cells divide, each egg cell gets a single X chromosome, and each sperm cell gets either an X chromosome or a Y chromosome. However, because of nondisjunction, an egg cell or a sperm cell can also end up with two extra copies of the X chromosome.

If an egg cell with two extra X chromosomes (XXX) is fertilized by a sperm cell with one Y chromosome, the resulting child will have 48,XXXY syndrome. Similarly, if a sperm cell with a Y chromosome and two extra X chromosomes (XXY) fertilizes an egg cell with a single X chromosome, the resulting child will have 48,XXXY syndrome.

Source: MedlinePlus Genetics

Diagnosis

Karyotype Test

Also called: Chromosome Analysis, Chromosome Karyotype, Chromosome Studies, Chromosome Testing, Karyotyping, Karyotype Genetic Test

A karyotype test is a type of genetic testing. It looks at the size, shape, and number of your chromosomes. Chromosomes are parts of cells that contain genes. If the number or structure of your chromosomes is not normal, it can indicate a genetic disease.

Karyotype Test

Also called: Chromosome Analysis, Chromosome Karyotype, Chromosome Studies, Chromosome Testing, Karyotyping, Karyotype Genetic Test

A karyotype test is a type of genetic testing. It looks at the size, shape, and number of your chromosomes. Chromosomes are parts of cells that contain genes. If the number or structure of your chromosomes is not normal, it can indicate a genetic disease.

{"label":"Karyotype Reference Range","scale":"lin","step":0.25,"hideunits":true,"items":[{"flag":"normal","label":{"short":"Normal","long":"Normal","orientation":"horizontal"},"values":{"min":0,"max":1},"text":"A normal human karyotype contains 22 pairs of autosomal chromosomes and one pair of sex chromosomes (allosomes). Normal karyotypes for females contain two X chromosomes and are denoted 46,XX; males have both an X and a Y chromosome denoted 46,XY.","conditions":[]},{"flag":"abnormal","label":{"short":"Abnormal","long":"Abnormal","orientation":"horizontal"},"values":{"min":1,"max":2},"text":"If you have more or fewer chromosomes than 46, or if there is anything unusual about the size or shape of your chromosomes, it can mean you have a\u00a0genetic disease. <br \/>\n<br \/>\nIf you were tested because you have a certain type of cancer or blood disorder, your results can show whether or not your condition is caused by a chromosomal defect.","conditions":["Chromosome abnormalities","Sex chromosome abnormalities","45,X\/46,XY mosaicism","47,XYY syndrome","48,XXXY syndrome","48,XXYY syndrome","49,XXXXY syndrome","Down syndrome (47,XX,+21 or 47,XY,+21)","Edwards syndrome (47,XX,+18 or 47,XY,+18)","Klinefelter syndrome (47,XXY)","Patau syndrome (47,XX,+13 or 47,XY,+13)","Turner syndrome (45,X)"]}],"value":0.5}[{"normal":0},{"abnormal":0}]
Use the slider below to see how your results affect your health.
Your result is Normal.
A normal human karyotype contains 22 pairs of autosomal chromosomes and one pair of sex chromosomes (allosomes). Normal karyotypes for females contain two X chromosomes and are denoted 46,XX; males have both an X and a Y chromosome denoted 46,XY.
Related conditions
A karyotype test is a type of genetic testing. It looks at the size, shape, and number of chromosomes in a sample of cells from your body. Chromosomes are found in the cell nucleus, which is like the command center of a cell. Chromosomes contain your genes. Genes carry information, called DNA, that controls what you look like and how your body works.
You inherit your chromosomes from your parents. Normally, all your cells (except for egg and sperm cells) have a set of the same 46 chromosomes. The chromosomes are grouped into 23 pairs. Each pair has two chromosomes, one coming from each parent. You may develop certain genetic disorders if your cells:
- Are missing whole chromosomes or pieces of chromosomes
- Have extra chromosomes or extra pieces of chromosomes
A karyotype test checks the chromosomes in your cells to:
- See whether you have a full set of 46 chromosomes. Having too many or too few chromosomes can cause serious problems with health, growth, and normal development, such as Down syndrome (extra chromosome 21) and Turner syndrome (missing X chromosome).
- Look for changes in the structure of chromosomes, such as broken, missing, or extra parts. These changes may cause a wide variety of problems depending on which chromosome is affected. But some changes in chromosomes don't cause problems.
Certain chromosome problems are present from birth. Chromosome problems can also develop in certain cells after birth. These problems can cause specific types of cancer.
Other names: genetic testing, chromosome testing, chromosome studies, cytogenetic analysis
A karyotype test looks for unusual changes in chromosomes. It may be used to:
- Check you and/or your family members for specific chromosome problems if you:
  Have a genetic disorder that runs in your family
  Have symptoms that may be from a genetic disorder
- Check an unborn baby for chromosome problems
- Find out if abnormal chromosomes are causing problems having children, including:
  Male or female infertility
  Miscarriages, if you have lost two or more pregnancies before 20 weeks
  Stillbirth
- Help diagnose and/or make treatment decisions for certain types of cancer and blood disorders
You may need a karyotype test if:
- You're planning to have children or are pregnant:
  To learn whether you and/or your partner have abnormal chromosomes that you could pass on to a baby
  To find out why you're having problems getting pregnant or having miscarriages
  To check your unborn baby for genetic disorders, especially if the baby has a high risk for problems. The risk may be high if:
  The pregnant parent is age 35 or older. The overall risk of genetic birth defects is small, but the risk increases after age 35.
  Either parent has a genetic disorder, a family history of a genetic disorder, or another child with a genetic disorder.
  The results of certain prenatal screening tests weren't normal.
- You have a family history of a chromosomal disorder and want to know your risk for developing the disorder.
- You and/or your child have symptoms of a genetic disorder. Each type of genetic disorder has different symptoms. Karyotype testing may be needed to make a diagnosis.
- You've been diagnosed with certain cancers or blood disorders that often involve changes in chromosomes. These changes can affect how your disease will behave and which treatment will work best for you. Karyotype testing may be needed to help diagnose and treat conditions such as:
  Leukemia
  Lymphoma
  Multiple myeloma
  Anemia
For a karyotype test, the type of sample you provide depends on the reason for the test.
To test the chromosomes of an unborn baby, the sample may be gathered using:
- Amniocentesis. This procedure collects a sample of the amniotic fluid that surrounds the unborn baby during pregnancy. The fluid contains cells from the baby that can be tested. Amniocentesis is usually done between week 15 and 20 of pregnancy.
- Chorionic villus sampling (CVS). This procedure collects tissue from the chorionic villi, which are parts of the placenta that usually have the same chromosomes as the unborn baby. (The placenta is the organ that grows in the uterus to provide nutrients and oxygen to the baby.) A CVS is usually done between week 10 and 13 of pregnancy.
To test the chromosomes of adults, children, and babies, the sample may be from:
- A blood test. This is the most common sample used for karyotype tests. A health care professional will use a small needle to remove a blood sample from a vein in your arm.
- A buccal (cheek) swab. A health care professional will insert a swab into your mouth and rub it across the inside of your cheek to gather a sample of cells.
- A bone marrow test. This test may be used if you have a certain type of cancer or blood disorder. Marrow is soft, spongy tissue found inside of bones. Most bone marrow samples are taken from the back of the hip bone.
1. Karyotype Genetic Test: MedlinePlus Lab Test Information [accessed on Nov 05, 2018]
2. https://labtestsonline.org/tests/chromosome-analysis-karyotyping [accessed on Nov 05, 2018]
3. 511035: Chromosome Analysis, Whole Blood (Constitutional) | LabCorp [accessed on Oct 03, 2018]
4. Chromosome Analysis, Blood (14596) [accessed on Oct 03, 2018]

Normal reference ranges can vary depending on the laboratory and the method used for testing. You must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

Additional Materials (1)

Chromosome Analysis - karyotyping

Video by Pathology Tests Explained/YouTube

2:36

Chromosome Analysis - karyotyping

Pathology Tests Explained/YouTube

Treatment

Zero / None / Null

Image by Clker-Free-Vector-Images/Pixabay

Zero / None / Null

Image by Clker-Free-Vector-Images/Pixabay

How Might 48,XXXY Syndrome Be Treated?

There is no cure for 48,XXXY syndrome. Treatment depends on the symptoms present in each individual and is best managed by a team of specialists, including cardiologists, orthopedists, speech therapists, neurologists, and endocrinologists. Life expectancy is generally normal in the absence of major complications. Regular medical visits are often needed, in particular to monitor problems with hormone production, infections, and behavior.

Source: Genetic and Rare Diseases (GARD) Information Center

Related HealthJournals

Genetic Testing

Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. Over 2000 tests are available. Genetic testing may be done for many reasons, from newborn baby screening to diagnosing certain diseases. Read about why you might consider testing.

Male Infertility

Infertility is generally defined as not being able to get pregnant after 1 year of unprotected sex. Read about the causes of male infertility, how it is diagnosed, and treatment options available.

Differences of Sex Development

Differences of sex development (DSD) represent a spectrum of congenital conditions in which the chromosomal, gonadal or phenotypic (anatomic) sex is atypical, meaning it doesn't fit the typical definitions of female or male. Some DSDs are more common than others. Learn about some of the more known DSDs.

Klinefelter Syndrome

Klinefelter syndrome (KS) is a condition that occurs in men who have an extra X chromosome. Most commonly, affected individuals are taller than average and are unable to father biological children (infertile). It is among the most common sex chromosome disorders and affects about 1 in 500 newborn boys. Read about the common symptoms and treatments.

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48,XXXY Syndrome

48,XXXY syndrome is a type of chromosome abnormality characterized by the presence of 2 extra X chromosomes in males. It is sometimes referred to as a variant of Klinefelter syndrome, but differs from Klinefelter syndrome in many ways and is more severe.

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