Klinefelter Syndrome

 

Klinefelter Syndrome:

Klinefelter Syndrome (KS) 47,XXY results from 2 or more X chromosomes in a phenotypic male. The clinical phenotype of KS was first described in males with tall stature, small testes, gynecomastia, and azoospermia, with the genetic etiology of supernumerary X chromosomes identified in 1959. Extra X chromosomes lead to testicular hyalinization, fibrosis, and testicular hypofunction, resulting in genital abnormalities, usually hypogonadism, and infertility. Neurocognitive differences associated with KS began to be recognized in the middle and later of the 20th century. Often, androgen replacement and neuropsychological and adaptive therapies are beneficial in the medical management of KS. However, deficits in clinical care do exist as there are gaps or delays in diagnosis, lack of standardization of care, and access to treatment is not always available or affordable. This activity reviews the evaluation and treatment of Klinefelter syndrome and the role of the interprofessional team in managing condition.

 

Signs and symptoms:

The Klinefelter syndrome has different manifestations and these will vary from one patient to another. Among the primary features are infertility and small, poorly functioning testicles. Often, symptoms may be subtle and many people do not realize they are affected. Whereas some other times symptoms are more prominent and may include weaker muscles, greater height, poor motor coordination, less body hair, gynecomastia (breast growth), and low libido. In the majority of the cases, these symptoms are noticed only at puberty.

Prenatal:

An estimated 60% of pregnancies with fetus having Klinefelter syndrome spontaneously abort. Generally, the severity of the malformations is proportional to the umber of extra X chromosomes present in the karyotype. For example, patients with 49 chromosomes (XXXXY) have a lower IQ and more severe physical manifestations than those with 48 chromosomes (XXXY).

 

Physical manifestations:

As babies and children, those with XXY chromosomes may have weaker muscles and reduced strength. They may sit up, crawl, and walk later than other infants. In average KS children will start walking at 18 months of age. They also have less muscle control and coordination than other children of their age.

During puberty, they show less muscular body, less facial and body hair, and broader hips. This is a direct consequences of the low levels of testosterone produced KS subjects. Delays in motor development may occur, which can be addressed through occupational and physical therapies. As teens, males with XXY may develop breast tissue, have weaker bones, and a lower energy level than others. Testicles of those affected are usually less than 2 cm in length (and always shorter than 3.5 cm), 1 cm in width, and 4 ml in volume. Those with XXY chromosomes may also have microorchidism (i.e., small testicles).

              By adulthood, they tend to become taller than average; with proportionally longer arms and legs, less-muscular bodies, more belly fat, wider hips, narrower shoulders. Some will show little to no sign of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia(increased breast tissue). Gynecomastia is present in approximately a third of affected individuals, a slightly higher percentage than in the XY population. Approximately 10% of males with XXY chromosomes have gynecomastia noticeable enough that they may choose to have surgery. Those affected are often infertile, or have reduced fertility. Advanced reproductive assistance is sometimes possible in order to produce an offspring since approximately 50% of males with Klinefelter syndrome can produce sperm.

Diagnosis:

The standard diagnostic method is the analysis of the chromosomes' karyotype on lymphocytes. A small blood sample is sufficient as test material. In the past, the observation of the Barr body was common practice, as well. To investigate the presence of a possible mosaicism, analysis of the karyotype using cells from the oral mucosa is performed. Physical characteristics of a Klinefelter syndrome can be tall stature, low body hair, and occasionally an enlargement of the breast. Usually, a small testicle volume of 1 - 5 ml per testicle (standard value: 12-30 ml) occurs. During puberty and adulthood, low testosterone levels with increased levels of the syndrome. A spermiogram can also be part of the further investigation. Often, an azoospermia is present, or rarely an oligospermia. Furthermore, Klinefelter syndrome can be diagnosed as a coincidental prenatal finding in the context of invasive prenatal diagnosis (amniocentesis, chorionic villus sampling). Approximately 10 % of KS cases are found by prenatal diagnosis.

The symptoms of KS are often variable, so a karyotype analysis should be ordered when small testes, infertility, gynecomastia, long arms/legs, developmental delay, speech/language deficits, learning disabilities/academic issues, and /or behavioural issues are present in an individual .

Treatment:

As the genetic variation is irreversible, no causal therapy is available. From the onset of puberty, the existing testosterone deficiency can be compensated by appropriate hormone-replacement therapy. Testosterone preparations are available in the form of syringes, patches, or gel. If gynecomastia is present, the surgical removal of the breast may be considered for both the psychological reasons and to reduce the risk of breast cancer.

The use of behavioral therapy can mitigate any language disorders, difficulties at school, and socialization. An approach by occupational therapy is useful in children, especially those who have dyspraxia.