Klinefelter Syndrome

Symptoms vary significantly between individuals—in some cases, there is noticeable impairment, while in others, they are subtle enough to be missed. Beginning with infancy, symptoms include:

• More passive infants than usual 
• Delayed ability to talk 
• Delayed ability to sit up and crawl (this is caused by weaker muscles and bone density)

In early childhood:

• Learning disabilities such as reading, writing and spelling difficulties 
• Lower attention span and difficulty concentrating
• Low energy levels 

In teenage years and adulthood:

• Delayed onset of puberty 
• Lack of facial hair 
• Taller than peers and the family norm 
• Poor muscle tone and muscle growth 
• Greater formation of breast tissue (gynecomastia) 
• Wider hips than average 
• Low sex drive 
• Inability to have children (infertility) 
• Increased belly fat
• Involuntary trembling (tremors)

Other symptoms of the syndrome may include:

• Cryptorchidism (undescended testes)
• Micropenis
• Dysmorphism (noticeably different facial features)
• Hypospadias (the opening of the urethra can be on the underside of the penis, rather than at the tip)
• Radioulnar synostosis (malformation in the forearm)
• Flat feet
• Curved little finger (clinodactyly)
• Cardiac anomalies
• Behavioural problems

As mentioned above, there is an increased risk of getting metabolic syndrome, a higher likelihood of male breast cancer, osteoporosis (thinning and weakening of bones), autoimmune disorders such as systemic lupus and rheumatoid arthritis. Blood vessel disease, heart and lung disease are also more likely to develop. Other developmental disorders include dyslexia and dyspraxia (difficulty coordinating one's movements). 

There is also comorbidity with mental health issues such as depression, anxiety, and ADHD (attention deficit hyperactive disorder). About 10% will also have autism spectrum disorder.

Please note that these symptoms and complications have been included to be comprehensive—in most cases, symptoms will be mind and assistive birth practices will help men live otherwise normal lives.

Klinefelter syndrome occurs when there is an extra copy of the X chromosome. As mentioned above, this is not an inherited disorder, so the risk of having a child with Klinefelter syndrome doesn't increase if the father has it. The extra X chromosome can develop naturally, due to random mutations either in the egg or sperm cells and get incorporated into the embryo. 

There may be different variations of chromosomal mutations but these are rare. If only some cells have an extra X chromosome, it is known as mosaic Klinefelter syndrome—this condition is less severe. On the other hand, there may be cases when there is more than one extra X chromosome in the cells, and these variants are more severe. 

1 in around 650 males is born with the disorder but it is very often undiagnosed as symptoms are mild. There is a slightly higher chance of this happening if the mother is over 35 years of age.

Since Klinefelter syndrome is not a deadly disorder and symptoms are often mild, many men will only get a diagnosis if and when they are unable to reproduce. Changes may be noticed over time and this history will be helpful in coming to a diagnosis. Testing involves many methods:

• Physical examination of the genital area and full body for developmental abnormalities.
• A full discussion of symptoms and onset of difficulties.
• Sex hormone testing will reveal if there is a low level of testosterone in the blood.
• Chromosome analysis, known as karyotype analysis, will reveal the number of chromosomes, and if there is an extra X chromosome. This is usually a confirmatory test.
• Amniocentesis: Some parents choose to have the fetus tested for possible genetic defects if there is a family history. Klinefelter syndrome can be picked up if this test is conducted.

There is no cure for Klinefelter syndrome since the gene mutation cannot be reversed. However, there are multiple therapies that can alleviate symptoms and prevent complications. If treatment is given on time, and depending on the degree of gene mutation, most men with Klinefelter syndrome will live a largely symptom-free and normal life. Treatments include:

• Testosterone replacement therapy (TRT): This involves taking medicines or injections containing testosterone to make up for the deficit in the body. TRT is usually begun at the onset of puberty and can help with the development of a deep voice, growing facial hair, increase muscle tone and mass as well as bone density and increase overall energy levels. There is also evidence that TRT can assist with developmental issues and behavioural problems. Furthermore, TRT can reduce the likelihood of osteoporosis in the adult years as well.
  TRT will not have an effect on infertility, however.
• Fertility treatment: This will be useful for those trying to reproduce. Intracytoplasmic sperm injection (ICSI) is a process by which sperm is removed from the testicle and transferred directly to the egg. For others, artificial insemination by a donor is an option as well. 
• Physiotherapy and speech therapy: Since those with Klinefelter syndrome may have low muscle mass, physiotherapy can help develop muscle strength, movement and utility. Speech therapists can help develop clearer speech as well.
• Breast reduction surgery: For those with greater breast tissue than normal, this surgery can give a more typical appearance to male breast tissue. It can also be done preventively for those who are concerned about breast cancer.
• Counselling: Unfortunately, those with Klinefelter syndrome are more likely to be depressed and feel isolated from their peers. They may be subject to bullying in school and neglected in adulthood. Psychotherapy can help those who develop mental health issues by developing more confidence and navigating their challenges. Further, occupational therapy can assist in performing daily chores and even build careers and develop key professional skills in those who need this support.