Understanding Klinefelter Syndrome

Klinefelter Syndrome – Misinformation And Misdiagnosis

IT should have been a happy time for James Miller. His career was thriving, and he and his wife Samantha (both in their 30s) had just celebrated their second wedding anniversary. But behind the smiles and celebrations, John had some sombre news: he had just been told he had a genetic problem and that he could never father children.

This bombshell came about after investigations for infertility (initially focused on Samantha) culminated with a sperm test that revealed no sperm, and triggered a genetic analysis. The consultation with his doctor was brief, but empathetic: “You have Klinefelter’s – it’s a problem where you have an extra X chromosome. I’m afraid there’s no chance of children – other than that, you will be fine.”

 Human male karyotype

Months passed, along with an almost daily unsatisfying internet trawl of the condition. It was not until the couple sought a fertility specialist (for donor sperm) that he was directed to an andrology specialist. After weeks of assessment and treatment, a sperm harvest was done, with good samples obtained for ICSI (intracytoplasmic sperm injection into the egg) for assisted reproduction.

Samantha is pregnant and they are now expecting their first child – almost three years since the diagnosis. “We were frustrated at first that we lost so much time – but we persisted and thankfully found a doctor specialising in this field. We now want to help educate both patients and other doctors about the condition and what lies ahead for sufferers,” says James.

“James was one of a few cases that pushed us to create a dedicated clinic for men with Klinefelter Syndrome,” explains Dr Tet Yap, consultant at Guy’s Hospital in London and one of the clinicians involved in his care. “The delays to see an appropriate clinician for the condition were unacceptable – imagine being told you have a life-changing diagnosis but not to worry about it.”

SO WHAT IS KLINEFELTER?

Klinefelter syndrome (KS) is one of the most common chromosomal disorders, occurring in 1 to 2 per 1,000 live male births. It is also one of the poorest diagnosed of the genetic conditions – it is estimated only 1 in 4 (25 per cent) of men with KS are ever diagnosed, usually because the signs and symptoms can be mild. However, the syndrome is also the commonest genetic cause of male infertility, accounting for 90 per cent of all genetically-based male infertility.

Genetics counsellor Charlotte Tomlinson from the Klinefelter’s unit at Guy’s (one of the first internationally) describes the condition: “Klinefelter syndrome (sometimes called Klinefelter’s, KS or XXY) is where boys are born with an extra X chromosome. Chromosomes are packages of genes found in every cell in the body; two types of chromosome, called the sex chromosomes, determine the genetic sex of a baby.

These are named either X or Y. Usually, a female baby has two X chromosomes (XX) and a male has one X and one Y (XY). But in Klinefelter syndrome, a boy is born with an extra copy of the X chromosome (XXY). The exact cause of the condition is not known, although there is a slightly increased risk in babies born to older mothers. KS is not an inherited condition, but is the result of an error during the fusion of reproductive cells (egg and sperm) from their parents when forming the embryo.”

WHAT ARE THE SIGNS OF KS?

In men with KS, the testes do not develop and are usually small. This leads to reduced testosterone production which can lead to a series of differences in development: delayed or incomplete puberty, enlargement of breast tissue (gynaecomastia) and reduced facial and body hair.

“One of the most common symptoms in adulthood is infertility,” says Dr Yap. “This is due to a gradual loss of the cells in the testes which are responsible for the production of sperm, and results in semen containing little or no sperm.” Consultant endocrinologist at St Thomas’ Hospital in London Dr Paul Carroll adds, “Many men are diagnosed as adults with KS because of their difficulties procreating.”

Fertility may also be time-limited: “Boys and men who are diagnosed earlier in life should be aware of what this could mean for their fertility in case they want to start a family later in their lives – there is some evidence that early intervention may be better at preserving fertility. This is an active area of research,” explains Dr Yap.

Besides infertility, adults with KS have an increased risk of developing Type 2 diabetes, osteoporosis (fragile bones), blood clots and autoimmune disorders (when your immune system mistakenly “attacks” your body) such as rheumatoid arthritis and systemic lupus erythematosus. This makes it vital that KS sufferers have a lifelong ‘plan’ beyond just fertility. “Life expectancy is usually normal, and many patients live normal lives”, says Dr Yap.

“However, low testosterone in KS men can give a series of symptoms: low energy levels, increased daytime sleepiness, low libido, and difficulty concentrating. These can be treated with testosterone supplementation.”

Guy’s Hospital London

HOPE AND THE FUTURE

“There is no cure for KS. However, there are treatments available for the problems associated with the condition,” explains Paula Allchorne, nurse practitioner in Men’s Health at Barts Hospital and now a part of the Guy’s Klinefelter clinic.

For example, testosterone replacement may help to prevent osteoporosis and improve low mood, concentration levels, energy levels, libido and self-esteem. “However, testosterone therapy does not improve sperm production and, if fertility is important, it should be delayed until after fertility issues have been addressed,” explains Allchorne.

For some men with KS who have no sperm in their semen, it is possible to take sperm directly from the testes with surgery called microTESE (microscopic testicular sperm extraction). “As technique and the work-up of men with KS becomes more refined and individualised, success rates of the sperm harvest are increasing, though they are currently at around 30 per cent,” explains Dr Yap.

An often-missed area of in the KS picture is the psychological support after diagnosis. “Genetic counselling is vitally important after the diagnosis,” says Alison Bridges, vice-chairperson of the Klinefelter Association (KSA) which gives support and information to all affected by KS, “and so is psychological counselling – an often-neglected part of the problem.”

With these issues in mind, new strategies in KS patient care are being pioneered in London and around the world.

The Klinefelter Syndrome Multi-Specialty at Guy’s Hospital is one of the first of its kind in the world – a one-stop clinic that covers all important aspects of the disease, with specialists in genetics, endocrinology, urology, reproductive medicine, psychology and radiology all seeing and counselling patients through the various aspects of the condition.

In addition, a member of the KS Association is on hand to give a personal view on living with KS. “A multispecialty approach like this is essential for conditions like KS”, says James. “Cutting down waiting times by months or years is important – and the anguish of not knowing what KS was is something I would never wish anyone else go through.”

Watch clip from ITV programme: New Clinic to help men with Klinefelter Syndrome

by Jake Lee

For more information please visit:  The Klinefelter Syndrome Clinic or The Klinefelter Syndrome Association

or email: health@theglassmagazine.com