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Klinefelter Syndrome (XXY Syndrome)
Klinefelter syndrome is a genetic condition in which a boy is born with an extra X chromosome. Instead of the typical XY chromosomes in men, they have XXY, so this condition is also called XXY syndrome.
Men with Klinefelter usually don't know they have it until they run into problems trying to have a child. There's no cure, but doctors can treat it.
You get the extra X chromosome by chance. Either the egg or the sperm that came together to create you had an extra X chromosome. Older women have a slightly higher chance of having a boy with XXY syndrome, but the chance is small.
Men with Klinefelter may have:
Some men show symptoms of Klinefelter in childhood, but others don't know they have it until puberty or adulthood. Many men never realize that they have it because symptoms aren't always present.
Symptoms of Klinefelter vary with age and include:
Babies:
Children:
Teenagers:
Adults:
To diagnose Klinefelter syndrome, your doctor will start with a physical exam and ask questions about your symptoms and general health. They'll probably examine your chest, penis, and testicles and do a few simple tests, such as checking your reflexes.
Your doctor may then run two main tests:
It's never too late to treat Klinefelter, but the earlier you start, the better.
One common treatment is testosterone replacement therapy. It can start at puberty and can spur typical body changes, such as facial hair and a deeper voice. It can also help with penis size and stronger muscles and bones, but it won't affect testicle size or fertility.
Testosterone replacement therapy throughout your life can help prevent some of the long-term problems that come with Klinefelter.
Other treatments include:
If your child has Klinefelter, things that might help include:
Many problems caused by Klinefelter are because of lower testosterone levels. You may have a slightly higher chance of:
Treatment can help boys and men with Klinefelter live happy, healthy lives. Advances in fertility treatments have made it possible for some to father children. In general, life expectancy is normal. Some research has found that life expectancy for men with the condition may be a year or two less than those without it because of other health problems linked to Klinefelter.
For men with Klinefelter syndrome, here are some tips:
Here are some ways that you can support your child with Klinefelter syndrome:
People with Klinefelter syndrome (XXY syndrome) are born with an extra X chromosome, which can affect their development. The condition may caus symptoms such as low muscle strength, less body and facial hair, and learning or social challenges. Treatments, especially when started early, can help improve symptoms. For example, testosterone therapy can support muscle growth, voice changes, and bone health. With medical support and therapy, you can lead a healthy life.
Who discovered Klinefelter syndrome?
Henry Klinefelter, an American physician, discovered Klinefelter syndrome condition in the 1940s, which was named after him.
Klinefelter's Syndrome
Overview of Klinefelter's SyndromeNormally, humans have 46 chromosomes, namely 22 pairs of autosomes and 1 pair of sex chromosomes. In females, both sex chromosomes are X chromosomes (XX), while in males, there is one X and one Y chromosome (XY).
Klinefelter's Syndrome (KS) is a sex chromosomal disorder like Turner's syndrome. While KS individuals have an extra X chromosome making the total number of chromosomes 47 in number, a person with Turner's lacks a X chromosome and has a total of 45 chromosomes.
Klinefelter's Syndrome, which affects 1 in 500 to 1 in 1000 live births, is a sex chromosomal genetic disorder where the affected males have an extra X chromosome. These individuals are also referred to as 'males with XXY syndrome', or as 'XXY males'. This is not an inherited disorder.
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Genetic variation in Klinefelter individuals show three to four extra X chromosomes, extra Y-chromosomes or mosaics.
Although most patients with Klinefelter's Syndrome have only one extra X chromosome in their cells, approximately 10% of the patients have different forms of the disorder. In a few rare cases, the affected individuals have three to four extra X chromosomes (48,XXXY or 49,XXXXY) or extra Y-chromosomes. Such patients are likely to suffer from severe abnormalities, including mental retardation and social behavioral problems. A majority of these patients are confined to mental or penal institutions.
In a small proportion of the Klinefelter individuals, a few of the body cells may be normal while the others may have an additional X chromosome. These individuals are referred to as mosaics. Depending on the proportion of the cells that are normal or affected, the symptoms may either be mild, moderate or severe.
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Klinefelter's Syndrome occurs as the result of an error during the formation of an egg or a sperm that results in a person having a XXY combination or 47 chromosomes instead of the normal 46.
Klinefelter's Syndrome is caused by the presence of an additional X chromosome. This error usually occurs when the chromosomes are distributed during the division of the egg or the sperm. In more than half of the cases, the extra X chromosome is contributed by the father.
Very little is known about the role of the mother's age in bringing about this condition. Women who are 35 and older have the greatest risk of having children with Klinefelter's syndrome. Scientists are not sure what other factors increase the risk as the error that produces the extra chromosome occurs at random.
The onset of adolescence in Klinefelter's Syndrome is marked by the lack of testosterone, poor growth of secondary sexual characters, gynecomastia and sterility. Sometimes there is dyslexia, delay in speech and development.
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Growth and Development
Newborns and children with Klinefelter's Syndrome appear completely normal. In the majority of the cases, such individuals are identified when they come to see the doctor for
The presence of small testes, absence of sperms in the ejaculate and reduced levels of the hormone testosterone is indicative of Klinefelter's Syndrome.
Poor development of secondary sexual characteristics such as reduced facial and body hair, poor muscular development and the presence of feminine traits, such as enlarged breasts, in the adult male is suggestive of KS.
A thorough physical examination of an individual with Klinefelter's Syndrome is performed and confirmed by diagnostic tests such as a Karyotype or a Buccal Smear test to look for the extra X chromosome.
Diagnostic tests need to be carried out to confirm the clinical analysis.
Diagnosis of Klinefelter's is confirmed by either of the two tests- a Buccal Smear or a Karyotype analysis.
Hormone testing
They check for abnormal hormone levels that are associated with the XXY syndrome. It is done by using a blood sample.The hormone levels that are checked are estradiol, follicle stimulating hormone, luteinizing hormone and testosterone.
Chromosome/ Karyotype analysis
It is also called Karyo type analysis. It checks for the XXY condition by looking at the number of chromosomes using special stains in a blood sample or in a buccal smear.
Semen examination
It is used to check fertility and measures the amount and quality of seminal fluid. It is also called a sperm count. It is performed by a fertility specialist.
Prenatal Diagnosis
Women who are 35 years and older or who have a family history of genetic conditions might have a chance to detect KS while looking for chromosomal abnormalities as a part of prenatal diagnosis.
Chronic Villus Sampling
It is a diagnostic test to check if all genetic conditions or chromosomes are present,
It is carried out when the woman is between 11 and 13 weeks pregnant. The procedure consists of a fine needle being passed through the stomach of the woman and into the womb to take a sample of the plasma and analyze it. The sample is known as chronic villi. It can be tested to prove if any chromosomal abnormalities are present.
Amniocentesis
It is a test carried out at a later stage when the woman is between 15 to 18 months of a pregnancy. It extracts amniotic fluid through a fine needle from the amniotic sac. The amniotic fluid acts as a security blanket around the unborn baby and it contains some cells that have been shred from the unborn baby, which can be used to examine its chromosomes.
Males diagnosed with Klinefelter syndrome should be seen by a team of specialists. The team may include general practitioners, pediatricians, endocrinologists, urologists, speech therapists, genetic counselors, and psychologists.
Testosterone therapy or replacement of the male sex hormone, testosterone, is the primary treatment for Klinefelter's Syndrome.
There is no cure for Klinefelter's syndrome. Treatment is used to correct some aspects of the condition and provide emotional support. As KS males are unable to produce sufficient quantities of testosterone, supplementation of this hormone is required.
Testosterone Replacement Therapy
It works by increasing the testosterone levels into the normal range. It helps improve bone density and reduces breast growth. But it cannot reverse infertility or increase testicle size. Testosterone is generally administered in the form of gels, injections or tablets.
It builds a more muscular body and promotes facial hair growth. It can be considered once puberty begins. Testosterone therapy must be initiated early in adolescence. The hormone is usually given through intramuscular injections, once in every 10 - 14 days.
It is common for the patients to have mood fluctuations or altered physical abilities during the treatment period. The dosage is started at 50 mg, which may be increased after a specified period.
Medications
Breast Reduction Surgery
Some males with Klinefelter's syndrome may develop excessive amount of breast tissue. Cosmetic surgery can be done to remove the extra tissue.
Speech-Language Therapy
Some but not all children with KS have language development and learning delays. They will have difficulty processing what they hear and might be slow in learning to talk, learn, read and write. A qualified Speech Language Therapist works with a patient on a one to one basis to improve communication skills.
Behavioral Therapy
Boys with Klinefelter's syndrome should be given a comprehensive psycho-educational evaluation (IPE) to plan appropriate educational resources and classroom placement. It will assess their learning strengths and weaknesses. Behavioral therapy can also teach social skills and productive ways to handle frustration, shyness and anger. They can help identify relationship problems and develop communication skills.
Infertility Treatment for Klinefelter's Syndrome PatientsIn Vitro Fertilization (IVF)
If you have Klinefelter's syndrome and are considering having children then you will have to visit the infertility specialist. Men with Klinefelter's syndrome mosaicism (46, XY/47,XXY) can be fertile. If you have viable sperm in your testes then it will be extracted and used for in-vitro fertilization(IVF)
Intra-Cytoplasmic Sperm Injection (ICSI)
ICSI involves an individual sperm directly injected into an egg. The egg containing the sperm is then placed inside the womb.
Physical Therapy
It will help patients improve their physical strength and mental coordination. A variety of exercises such as traction, stretches and massage are done during the therapy sessions. It is recommended for boys with hypotonia and delayed gross motor skills.
Parents of XXY males have also mentioned that taking part in physical activities at low key levels such as karate, swimming, tennis and golf were helpful in improving motor skills, coordination and confidence.
Occupational Therapy
It is advised for boys with motor dyspraxia, the therapist helps the child to learn skills to help him perform basic daily activities. The earlier the treatment begins the better the outcomes.
An individual with Klinefelter's Syndrome is more prone to developing cancer and immune system-related disorders.
A person with KS has an increased susceptibility to many conditions and these include:
There is an increased risk of developing immune system-related disorders such as rheumatoid arthritis, thyroid disease or systemic lupus erythematosis.
Early medical intervention and a supportive social climate promotes the well-being and overall prognosis of individuals with Klinefelter's Syndrome
Klinefelter's Syndrome, being a genetic disorder, is not curable. It can, however, be effectively managed with timely medical intervention and social support, enabling these individuals to live a near-normal life.
Parents and teachers should take every step to help the adolescent KS individuals to develop self-esteem and self-confidence. A warm and stimulating family and school environment early in life promotes the emotional growth of these individuals. Early diagnosis, support and appropriate counseling contribute towards improving the overall prognosis.
An Overview Of X-Linked Disorders And X Chromosome Aneuploidies
Numerical disorders of the X chromosomeX-Linked disordersDiagnosis of X chromosome disordersManagement and support for X chromosome disorders ReferencesFurther reading
Numerical disorders of the X chromosomeChromosomal abnormalities can include two basic categories: numerical or structural. A structural abnormality can include an alteration to the structure of the chromosome, as the name suggests. However, a numerical abnormality means that an individual is either missing one of the chromosomes from its pair or that the individual has more than two chromosomes.1
The number of chromosomes in the human cell includes 46, with 23 pairs, one set being inherited from the egg provided by the biological mother and the other set of 23 chromosomes being inherited from the sperm provided by the biological father.1
The first 22 pairs are known as autosomes, whereas the final pair are called "sex chromosomes," which determine an individual's sex, with a female having two X chromosomes (XX) and a male having both an X and Y chromosome (XY).1,2
Numerical abnormalities are more common than structural abnormalities, with these mutations in sex chromosomes having different implications compared to autosomes.2
Image Credit: Anusorn Nakdee/Shutterstock.Com
Having an abnormal number of chromosomes in a cell instead of 46 is known as aneuploidy. Sex chromosome aneuploidies can lead to diseases such as (i) Klinefelter's syndrome, (ii) Triple X syndrome (Trisomy X), and (iii) Turner syndrome.2
Klinefelter's syndromeKlinefelter's syndrome consists of an abnormally higher number of chromosomes than the usual 46 total chromosome number, consisting of 47 chromosomes in more than 90% of cases, which have XXY chromosomes. However, other karyotypes can include, but are not limited to, 48 chromosomes (XXXY) and 49 chromosomes (XXXXY).2
This disease affects males, with the incidence being reported as being between 1 in 500 cases and impacting 1:1,000 male births. Klinefelter's syndrome can result in being taller than average, having long extremities, delayed and incomplete puberty, small testes and testicular atrophy, infertility, enlarged breast tissue, and an increased risk of breast cancer.2
Additionally, these males also display less facial and bodily hair and developmental delay, including having learning disabilities as well as having delayed speech and language development.2
The prognosis of these males is also variable depending on the severity of the clinical manifestations and treatment; however, it is still fairly good, with a slightly reduced lifespan.2
Triple X syndrome (Trisomy X)Another chromosomal alteration impacting sex chromosomes includes Triple X syndrome or Trisomy X, which impacts 1 in 1,000 females from birth due to having 47 chromosomes in total, with an extra X chromosome (XXX).2
Females with this chromosomal abnormality grow to be taller than the average height, as well as other potential effects such as delayed development of speech, language, and motor skills, weak muscle tone, seizures, behavioral and emotional challenges, and kidney abnormalities. However, some cases of this syndrome may appear to be phenotypically normal.2
Like Klinefelter's syndrome, the prognosis of Triple X syndrome is also variable, depending on its severity and treatment, but it is fairly good overall.2
Turner syndromeTurner syndrome is known to be the most common sex chromosomal abnormality in females, as well as the most common genetic cause of primary amenorrhea, which includes the absence of menstruation in girls by the age of 15.2
Illustration of Turner Syndrome, a genetic condition characterized by the loss or abnormality of one X chromosome, leading to specific physical traits and health challenges. Image Credit: Pepermpron/Shutterstock.ComThis abnormality results in 45 chromosomes in total in 45% of cases due to the majority of zygotes being unable to survive the external world after being born. However, other cases can also include different total chromosomal numbers, including 46 and 47 chromosomes.2
The incidence of this disorder includes approximately 1 in 2,000 to 1 in 2,500 live females at birth, with significant effects such as reduced height and short stature. Additionally, this disorder can cause females to have low posterior hairline, absence of menstruation, infertility, skeletal abnormalities, congenital kidney or heart disease, and lymphedema.2
Turner syndrome also consists of an overall good prognosis; however, this is variable depending on the severity of clinical manifestations and treatment.2
X-Linked disorders Hemophilia BX-linked inheritance is determined by a gene on the X chromosome, with X-linked recessive disorders typically manifesting only in males, while X-linked dominant disorders affect both sexes.3
Hemophilia B is an example of an X-linked disorder. It is a rare hematological disorder that causes spontaneous or prolonged hemorrhages as a result of a deficiency in the clotting IX factor. This disorder impacts less than 5,000 people in the U.S. And can manifest from birth to childhood.4
Hypophosphatemic ricketsAnother X-linked disorder example includes hypophosphatemia (XLH), which most commonly causes hypophosphatemic rickets and impacts 1 in 20,000 people.5
What is X-linked Recessive Inheritance?Play
Hypophosphatemia occurs when there are genetic defects in the sodium-phosphate cotransporters in the kidneys or their regulators, which can impair the reabsorption of filtered phosphate. Persisting impairment of this function in children can lead to rickets, which can cause dysfunction in mineralizing growing bones due to phosphate being required with calcium to form hydroxyapatite for the mineralization of bones.5
The most common cause of rickets is usually nutritional vitamin D deficiency or reduced calcium intake. However, hypophosphatemic rickets is a genetic disorder.5
Mohr-Tranebjaerg syndromeMohr-Tranebjaerg Syndrome (MTS) is a rare X-linked neurodegenerative disorder that causes early-onset hearing loss, gradual and progressive dystonia (uncontrolled muscle spasms), and optic atrophy. This disorder is caused by mutations in the nuclear TIMM8A gene, which plays a role in the mitochondrial transport of metabolites. Its association with multiple systems has also led to frequent occurrences of psychiatric disorders in these patients, such as dementia and mental retardation.6
Interestingly, less than 100 cases of MTS have been reported since its first description in a family in 1960.6
Opitz-Kaveggia syndromeOpitz-Kaveggia Syndrome or FG Syndrome 1 (FGS1) comprises characteristics such as developmental delay, facial abnormalities including a large head and down slanting eyes, and poor muscle tone from birth. FGS1 can also impact other bodily systems, such as genitourinary, gastrointestinal, and musculoskeletal systems.7
The prevalence of this disorder is unknown; however, it is caused by a mutation in the MED12 gene, which leads to the complete or partial absence of the corpus callosum that connects the two hemispheres of the brain.7
Diagnosis of X chromosome disordersTwo main methods can be used to diagnose these X chromosome disorders: (i) karyotyping and (ii) fluorescent in-situ hybridization (FISH).2
KaryotypingKaryotyping is considered to be the most definitive method for identifying chromosomal abnormalities, with this process requiring cells to be inoculated and cultured for 10 to 11 days, with diagnosis rates including 97.8% for chorionic villus sampling and 99.4% for amniocentesis. This method is considered to be the "gold standard" for diagnosing fetal aneuploidies in amniotic fluid samples.2
However, there are disadvantages to this method, such as requiring cells to be in the metaphase stage of the cell cycle, which does not always occur with sufficient quality for accurate quantification of chromosomes. Additionally, the time scale of karyotyping is 1-2 weeks.2
Fluorescent in-situ hybridizationThe second type of testing method includes FISH, which uses fluorescent-labeled DNA probes to assess the complementary DNA sequence of interest in the genome by hybridization, investigating its presence, location, and copy number. This method is relatively fast when identifying structural chromosomal abnormalities with small regions of DNA.2
FISH technology has also advanced other techniques, leading to powerful analytical tools such as spectral karyotyping, multicolor FISH, and comparative genomic hybridization.2
Early detection of chromosomal disorders is significant as approximately 0.4% to 0.9% of newborns are born with chromosomal abnormalities, with an estimated half having an abnormal phenotype.2
Knowledge of these chromosomal abnormalities is essential for informed choice and prevention strategies, as well as effective management of symptoms, including genetic counseling.2
Management and support for X chromosome disordersThere are various management strategies available for X chromosome disorders, including hormone therapy, with support also being available for how to manage any side effects.8
Additionally, a survey of adolescents and young adults with Klinefelter's syndrome found approximately one-third of the sample experienced psychological challenges, including depression, anxiety, low self-esteem, and mood instability.8
Genetic counseling and specialized medical care can be useful to support families and patients who are struggling with their diagnosis, including seeing behavioral specialists and psychiatrists.8
Specialty referral to reproductive gynecological care specialists can also be helpful for those concerned about fertility when patients are of age. However, for some infertile patients, discussing infertility at an age-appropriate time is also significant and may require extra support from healthcare professionals.8
References
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