Klinefelter Syndrome

Original Editor - Shaymaa Merazy
Top Contributors - Kim Jackson

Introduction[edit | edit source]

Klinefelter syndrome is a genetic condition affecting males, and it often isn't diagnosed until adulthood, results when a boy is born with an extra copy of the X chromosome.

Klinefelter syndrome may adversely affect testicular growth, resulting in smaller than normal testicles, which can lead to lower production of testosterone. The effects of Klinefelter syndrome vary, and not everyone has the same signs and symptoms.

Most commonly, affected individuals are taller than average are unable to father biological children (infertile); however, the signs and symptoms of Klinefelter syndrome vary among boys and men with this condition. In some cases, the features of the condition are so mild that the condition is not diagnosed until puberty or adulthood, and researchers believe that up to 75 percent of affected men and boys are never diagnosed[1].

Most men with Klinefelter syndrome produce little or no sperm, but assisted reproductive procedures may make it possible for some men with Klinefelter syndrome to father children.


Causes[edit | edit source]

Klinefelter syndrome occurs as a result of a random error that causes a male to be born with an extra sex chromosome. It isn't an inherited syndrome[3].

Most often, Klinefelter syndrome is caused by a single extra copy of the X chromosome, resulting in a total of 47 chromosomes per cell. Males normally have one X chromosome and one Y chromosome in each cell (46, XY), while females have two X chromosomes (46, XX).[4]

An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes[5]. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result of nondisjunction[4]. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have one extra copy of the X chromosome in each cell (XXY), the most common cause, or more extra X chromosomes in each of the body's cells which is rare and known as "variants of Klinefelter syndrome(48, XXXY, 48, XXYY and 49, XXXXY) and results in a severe form[5].

People with Klinefelter syndrome usually have two X chromosomes and one Y chromosome (47, XXY). Some people with Klinefelter syndrome have the extra X chromosome in only some of their cells; these people are said to have mosaic Klinefelter syndrome with fewer symptoms.

It is estimated that about half of the time, the cell division error occurs during the development of the sperm, while the remainder is due to errors in egg development. Women who have pregnancies after age 35 have a slightly increased chance of having offspring with this syndrome[3][5].

Incidence[edit | edit source]

It is estimated that 1 in every 500 to 1,000 newborn males has an extra X chromosome, making Klinefelter syndrome one of the most common chromosomal disorders seen among newborns. Variants of Klinefelter syndrome (such as 48, XXXY, 49, XXXXY) are much rarer, occurring in 1 in 50,000 to 1 in 85,000 or fewer newborns[5].

Other Medical or Scientific Names[edit | edit source]

  • 47,XXY
  • XXY syndrome or condition
  • XXY trisomy[4]
  • 47, XXY/46, XY or mosaic syndrome (rare variation)
  • Poly-X Klinefelter syndrome, including the following rare variations:
  1. 48, XXYY (or tetrasomy)
  2. 48, XXXY (or tetrasomy)
  3. 49, XXXXY (or pentasomy)[6][3]

Signs and Symptoms[edit | edit source]

The signs and symptoms vary among affected people[4]. Some men with KS have no symptoms of the condition or are only mildly affected. In these cases, they may not even know that they are affected by KS. When present. Whether or not a male with KS has visible symptoms depends on many factors, including how much testosterone his body makes, if he is mosaic (with both XY and XXY cells)[7], and his age[4] when the condition is diagnosed and treated.

Symptoms may include:

  • Small, firm testicles that produce a reduced amount of testosterone (primary testicular insufficiency)[1].
  • Delayed or incomplete puberty due to the shortage of testosterone with lack of secondary sexual characteristics resulting in sparse facial, body, or sexual hair[1] a high-pitched voice, and body fat distribution resulting in a rounder, lower half of the body, with more fat deposited in the hips, buttocks, and thigh instead of around the chest and abdomen[5].
  • Breast enlargement (gynecomastia)[1][5] in 30% of cases.
  • Reduced facial and body hair[1].
  • Infertility due to low sperm count[4].
  • Tall stature[1][5].
  • Abnormal body proportions (long legs, short trunk, shoulder equal to hip size).
  • Learning disability[5].
  • Speech delay[1][5].
  • Cryptorchidism (undescended testes)[1][5].
  • Opening (meatus) of the urethra (the tube that carries urine and sperm through the penis to the outside) on the underside of the penis (hypospadias)[1] instead of the tip of the head of the penis[5].
  • Social problems as anxiety, depression, and impaired social skills[1].
  • Intellectual disability[5].
  • Distinctive facial features[5].
  • Reduced muscle mass[1] and osteoporosis(25% of the patients had reduced bone mass up to 15%).
  • Poor coordination[1][5].
  • Hypotonia[1][7].
  • Severe speech difficulties[1].
  • Tendency to have better receptive language skills (the ability to understand speech) than expressive language skills (vocabulary and the production of speech)[1].
  • Behavioral problems[1] such as emotional immaturity and impulsivity and limited problem-solving skills (executive functioning)[1].
  • Heart defects[5].
  • Metabolic syndrome (Nearly half of all men with Klinefelter syndrome)[1][4].
  • Teeth problems[5].
  • Other differences can include abnormal fusion of certain bones in the forearm (radioulnar synostosis), curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus)[1].
  • Many anomalies related mostly to the skeletal system[5], such as cubitus varus, pigeon chest, or iliofemoral articulation degeneration.
  • Slightly increased risk of developing breast cancer(if gynecomastia develops)[5], a rare extragonadal germ cell tumor, lung disease, varicose veins, and osteoporosis as well as some autoimmune disorders such as systemic lupus erythematosus[4], rheumatoid arthritis[1][4], and Sjogren's syndrome[7].
  • Increased risk of developing involuntary trembling (tremors)[1].
  • Autism Spectrum Disorder (10% of all boys and men with Klinefelter Syndrome)[1].
  • Shank varices with ulceration of a significant degree (a consequence of chronic venous insufficiency ) 6 to 13% of cases[7].
Klinefelter's syndrome symptoms.jpg

Diagnostic Procedures[edit | edit source]

Three simple tests can be carried out to provide an accurate diagnosis of this condition[8].

Klinefelter's Syndrome XXY DNA karyotype.jpg
  • Karyotype test can give us information about the number of chromosomes present in the cells.
  • Hormonal analysis can inform us about the existence of a testosterone deficit due to hyperandrogenism, and there is an elevation in FSH and LH levels.
  • Semen analysis can help determine if the patient has azoospermia or could have children with fertility treatment[8].

Management / Interventions[edit | edit source]

When a diagnosis is made, treatment is based on the signs and symptoms present in each person.The first step which gives the opportunity to deal with the negative consequences of the Klinefelter syndrome, initially undertaken by the doctors, is to balance the testosterone deficiency.

Testosterone replacement
[4]: About half of people with SK have low testosterone levels, which may be raised by taking supplemental testosterone which can help affected people develop bigger muscles, a deeper voice, and facial and body hair, and may also increase sexual desire, enlarge the testes, improve mood, self-image, and behavior; it may also protect against osteoporosis and decrease the risks of autoimmune disease and breast cancer[7].

Breast removal or reduction surgery[7].

Educational interventions: As children, many people with Klinefelter syndrome qualify for special services to help them in school. Teachers can also help by using certain methods in the classroom, such as breaking bigger tasks into small steps. Individual education is essential to introduce individual education which may improve the effectiveness of teaching, increasing general activity, and motivation to take action. The Good Start Method can be employed. This method makes use of visual stimuli, such as graphic signs or pictures, or auditory stimuli, such as a song or melody[7].

Psychotherapy in Klinefelter’s syndrome plays a very important role in the quest for orienting on strengthening the neurotic, threatened in the social environment ‘Me’, which helps with the self-acceptance, reduces the feeling of anxiety and facilitates functioning within a family.

Several forms of therapy such as physical, speech, occupational, behavioral, mental health, and family therapy can often help reduce or eliminate some of the symptoms of Klinefelter syndrome. A multidisciplinary team is needed[7].

Physiotherapy[edit | edit source]

For the shank ulceration:

  • compressotherapy .
  • lymphatic massage .
  • Ultrasounds in the water bath of 34°C temperature .
  • Magnotherapy:magnetic field of low frequency for all chronic wounds.
  • Low level laser[7]

For the peripheral circulation treatment High voltage electrotherapy may also be used[7]:

For negative attitudes and anxiety:

  • Classic massage by supportive agents such as aroma oils[7].

For osteoporosis :

  • balance training.
  • breathing exercise.
  • Later exercises improving the deep stabilization.
  • Exercises improve maintaining balance.
  • Various forms of sensorimotor training.

It is recommended to exercise large groups of muscles, such as abdominal muscles, back muscles, muscles of the pectoral and pelvic girdle as well as exercises performed in a water environment which are a deloading factor[7].

For anomalies related to the skeletal system:

  • Preventive treatment.
  • Correction of the resultant changes at later stage .
  • Total conditioning exercises to improve the locomotor system.
  • Strengthening excercises.
  • Endurance exercises.
  • Resistance exercises; overload cannot exceed 50% of the maximal strength and the exercises should be performed with no isometric work.

The training should not be monotonous.

The exercises need to be modified, preferably every day, so that they give satisfaction and are a form of relaxation.

The exercises should be a form of whole body rehabilitation[7].

For psychomotor development:

Breathing exercises: a form of rehabilitation that affects multidimensionally and effectively not only the respiratory system but also cardiovascular and nervous systems, improving the quality of functioning of the musculoskeletal-ligamentous system[7].

Occupational Therapy[edit | edit source]

The final element of rehabilitation, which acts on many levels. It is necessary in some cases of men suffering from this disease, since their sense of social rejection. It should facilitate them joining in everyday social life. In the case of those men, the professional work adjusted to their disability is essential[7].

References[edit | edit source]

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 Genetic Testing Registry. Klinefelter-syndrome, XXY. Available from: https://www.ncbi.nlm.nih.gov/gtr/conditions/C0022735/ (accessed 5 October 2020).
  2. Klinefelter Syndrome - Usmle step 1 Genetic diseases. Available from:https://www.youtube.com/watch?v=R-jqm7KXd0s&feature=youtu.be. (Last accessed 06/10/2020)
  3. 3.0 3.1 3.2 Genetic Conditions. Klinefelter Syndrome. Available from: https://medlineplus.gov/genetics/condition/klinefelter-syndrome/ (accessed 5 October 2020).
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 Patient Care & Health Information,Diseases & Condition. Klinefelter Syndrome. Available from: https://www.mayoclinic.org/diseases-conditions/klinefelter-syndrome/symptoms-causes/syc-20353949/ (accessed 5 October 2020).
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 U.S. Department of Health & Human Services. Klinefelter-syndrome. Available from: https://rarediseases.info.nih.gov/diseases/8705/klinefelter-syndrome (accessed 5 October 2020).
  6. US Department of Health and Human Services. Klinefelter-syndrome(KS). Available from: https://www.nichd.nih.gov/health/topics/klinefelter/ (accessed 3 October 2020).
  7. 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 Myśliwiec A, Knapik H, Pasek A, Kuszewski M, Saulicz M, Ryngier P, Wolny T. Rehabilitation of patients with the Klinefelter’s Synndrome-review of available literature. Journal of Health Sciences. 2011;1(2):089-99.
  8. 8.0 8.1 Ferradas ER, de Pablo JL, Salvador Z, Fernández S. Klinefelter Syndrome (XXY Syndrome)–Symptoms, Causes & Fertility.(2020) Available from:https://www.invitra.com/en/klinefelter-syndrome/diagnosis-of-klinefelter-syndrome/ accessed on (5 October 2020)