Dr Muhammad Arshad and Prof Michael Fitzgerald write about the causes of and the treatment options for Klinefelter’s syndrome, a trisomy disorder that is found in approximately one in 700 male births.
Klinefelter’s syndrome (KS) is the most common cause of hypogonadism and the second most common trisomy disorder. It was named after Dr Harry Klinefelter in 1942, who first described a group of symptoms (enlarged breasts, small testes, inability to produce sperm, sparse facial and body hair) in males with the extra X chromosome.
KS is found in approximately one of 700 male births. A normal human karyotype consists of 46 chromosomes with an XX for females and an XY for males. KS is a chromosomal abnormality characterised by the presence of an extra copy of X chromosome, leading to 47 XXY chromosomes.
The extra X chromosome is retained because of a nondisjunction event during meiosis or mosaicism 47, XXY.
h4. Characteristics
Physical development:
Babies with KS have weak muscles with reduced strength and may sit up, crawl and walk later than other infants. After age four, they tend to be taller and have less muscle control and co-ordination than other boys their age.
During puberty, testosterone production is very low, which leads to abnormal body build (long legs, short obese trunk), tall stature, having less muscular body, overweight, feminine distribution of pubic hair, sparse facial and body hair, larger breasts (gynaecomastia), weaker bones and broader hips than other boys. Testicles of boys with KS are of normal size at birth. Teenagers have small penis, prostate gland and testicles which remain only 2cm from pole to pole (micro-orchidism). Few sperm are developed in the testicles, and do not produce enough testosterone.
Men with KS have sexual dysfunction (impotence, lack of libido), but usually make little or no sperm and between 95-99 per cent are infertile.
Language development:
Males with KS (25-85 per cent) exhibit delayed language milestones, such as learning to talk late, expressive dysphasia, dyslexia, processing what they hear and show low IQ with moderate to severe mental retardation.
Personality and social development: Babies with KS tend to be quiet and undemanding. During the teenage years, they are usually shy, quieter, less active and more obedient than other boys. They may struggle in school and sports, and may have problems fitting in. Yet during adulthood, many patients with KS can go on to have normal social relationships.
Psychiatric symptoms: A few men show aggressive behaviour due to frustration, and there is an increased incidence of ADHD and depression.
Cardiovascular system:
There is increased incidence of mitral valve prolapse, chronic leg ulcers and cardiovascular disease due to increased cholesterol levels.
Immunological system:
Incidence of autoimmune diseases like lupus, diabetes mellitus, rheumatoid arthritis and thyroid are increased.
Oral problems: Taurodontism (enlarged tooth size with reduced root size) and early tooth decay may occur.
Complications
Patients with KS have a 50 times greater risk of extragonadal germ cell tumours in the mediastinum, with respiratory symptoms, and 20-30 times the risk of breast cancer.
Differential diagnosis
Hypogonadism affects about five in every 1,000 men and its symptoms are: loss of libido, impotence, reduced facial hair, tiredness, reduced muscle power, increased fat, breast development, azospermia, infertility, osteoporosis, dry skin, depression and heart disease.
Prenatal screening and diagnosis
Prenatal screening includes amniocentesis (fluid surrounding the foetus is withdrawn to check for chromosomal abnormalities) and chorionic villus sampling (foetal cells taken from placenta). Diagnosis should measure low serum testosterone, urinary 17-ketosteroid levels, high serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels. Testosterone concentrations in the blood are at their highest between 8-10am and lowest at about 10pm (normal range 10-35nmol/l).
Management
Prompt recognition and management significantly improves the patient’s quality of life. The 47 XXY chromosome pattern cannot be changed as the genetic variation is irreversible, but its symptoms can be altered or treated in a number of ways, including testosterone treatment and other therapies.
Other supports can include speech therapy, education support special services, psychological therapies, regular breast checks and finally, physiotherapy (for muscle development and motor function). Surgery can correct gynaecomastia.
Genetic counselling for termination for pregnancy, adoption and infertility treatment such as intracytoplasmic sperm injection has now been developed to enable some patients to have biological children.
Lifelong testosterone replacement therapy may be indicated when serum concentrations are low, and should be initiated as soon as possible.
Boys with KS should be treated with testosterone, from 11-12 years of age, which increases masculinity, strength, libido, bone mineral density and body hair. It reduces the risk of breast cancer and osteoporosis later in life.
* Dr Muhammad Arshad, Hawkes Bay Hospital, New Zealand and Prof Michael Fitzgerald, Henry Marsh Professor, TCD.
About Gary Culliton
Loading ...
