We are holding a patient meeting for KS / CHH patients at the Royal Free Hospital in London on the 6th August 2016.
Attending the meeting will be two experienced KS clinicians and researchers from the KS clinic at CHUV, Switzerland, Prof Nelly Pitteloud and Dr Andrew Dwyer.
It will be a good chance to meet fellow patients in a relaxed, friendly environment and to ask experienced KS experts any questions you may have. Since KS / CHH are such rare conditions many patients do not get the chance to meet another person with the same condition. It can be a very beneficial experience to be able to meet and talk to fellow patients of different ages.
The meeting is to be held in the seminar room of the Medical School Library on the ground floor of the Royal Free Hospital, Hampstead in North London. The meeting will start at 11am and last until about 5pm.
Letter from Genetic Alliance UK regarding genetic screening for couples with Kallmann syndrome undergoing fertility treatment.
We are doing a piece of work relevant to you, and hoped you might like to be involved.
The Human Fertilisation and Embryology Authority (HFEA) has received an application to licence preimplantation genetic diagnosis (PGD) for Kallmann syndrome. This means that a couple in the UK with a family history of the condition have applied to use PGD to conceive achild who would be free from the disease. You can find out more about the reproductive technique, preimplantation genetic diagnosis, here, and the HFEA call for information on this condition here.
When the HFEA committee makes a decision on whether to licence PGD they make this decision based on whether they think that the condition is ‘sufficiently serious’. We provide statements to the HFEA detailing the effects on an individual from the perspective of patients (rather than the clinical aspects of a condition). To fairly represent the ways that some patients could be affected by the condition, we outline the worst case scenario for those affected.
We hope to provide some patient voice on the issue, and to aid us in this work have developed a survey which we would be really grateful if you could fill in. If you feel it is appropriate we would also encourage you to disseminate the survey to patients with the condition (and their families and carers). We feel that it is really important for patients to have a voice in the process of licensing for this reproductive technique, and your input would be invaluable in this.
The answers from the survey will be used to develop a statement detailing the way that the condition affects those who have the condition from a social and psychosocial point of view. This would then be submitted as evidence to be considered by the licensing committee at the HFEA. We would, of course, be happy to submit this jointly with your organisation.
This is a very interesting area of research I think.
There are basically two types of KS / CHH. One is where the GnRH releasing neurones have been blocked in their migration into the hypothalamus during early development, which normally results in Kallmann Syndrome cases as the olfactory (sense of smell) nerves are blocked as well.
The other type is where the action of the hypothalamus is impaired. The GnRH releasing neurones are in the right place but for some reason they do not fire in the correct manner to allow GnRH to be released correctly (called a pulse generator). This normally results in CHH where the olfactory nerves are unaffected and there is a normal sense of smell.
Whether you get a case of KS or CHH will depend on which gene or genes have been affected and where in the developmental process they have an effect.
An active area of research at the moment is looking in how the genes involved in the action of the hypothalamus operate and how they are influenced by external factors such as nutrition, stress, environment or even sexual activity. This is known as epigenetics,
There are research groups looking to see if the reproductive cycle can be restored by switching on genes that are present but are not active by modifying external factors. It is certainly early days in terms of research but the more reversal cases they find the more chance they have of finding out crucial information which will increase the understanding of KS / CHH.
Reversal is less common in KS cases where there are less GnRH nerve cells inside the hypothalamus but reversal cases have be reported. There is a theory that GnRH neurones continue to grow / move throughout life and if the eventually reach the hypothalamus in sufficient numbers the reproductive cycle can start later in life.
The reversal is always fragile and the hypogonadal state can return in some cases but it does provide a little bit of hope.
It is good to know research is ongoing in this area.
This diagram (with thanks to Prof Nelly Pitteloud, CHUV) shows the schematic layout of the causes of Kallmann syndrome or congenital hypogonadotropic hypogonadism with the migration of GnRH neurones and some of the gene defects that are linked to the two conditions.
Listed are 16 of the currently 25 known genes, defects in which, are known to cause cases of KS or CHH and the location where these genes have an effect.
Seven of the genes (KAL-1, FGFR1, FGF8, PROKR2, PROK2, CHD7, NELF) are involved in the development and migration of the GnRH releasing neurones. These neurones are supposed to migrate along the same channel as the olfactory axons from a structure called the olfactory placode until they meet up with the hypothalamus.
This normally takes place around week 10 to 14 of embryonic development. If one of these genes are affected the passage of both the olfactory axons and GnRH neurones can be blocked which results in the anosmia and GnRH deficiency seen in Kallmann syndrome. The olfactory bulb is not fully formed, which can be observed in an MRI scan and the hypothalamus is unable to release GnRH which prevents puberty and the reproductive cycle from occurring.
The remaining genes listed (DAX1, PC1, LEPR, LEP, KISS1R, FGFR1, PROKR2, PROK2, TACR3, TAC3, GNRH1) are involved in the correct regulation of GnRH secretion from the hypothalamus. Some of the genes listed affect both the migration of the GnRH neurones and the regulation of the GnRH release.
The genes that are involved purely in the regulation of GnRH secretion have no effect on the migration of the GnRH neurones or olfactory axons, so the olfactory bulb is correctly formed which results in a normal sense of smell, this condition is called congenital hypogonadotropic hypogonadism (CCH).
The hypothalamus has to release GnRH in a specific pulsatile manner in order for the pituitary gland to be able to release FSH / LH which will initiate puberty and the reproductive cycle. If this pulsatile release of GnRH is impaired it will prevent the correct release of FSH / LH (known together as the gonadotropins) and the reproductive cycle will break down.
One final gene listed is GNRHR. A defect in this gene prevents the pituitary gland from being able to recognise the GnRH secreted from the hypothalamus so it also prevents the release of LH and FSH from the pituitary gland.
There are more gene defects that can be added to this diagram with over 25 known implicated genes at the time of writing.
Knowledge of which genes are involved in a particular case can give an indication on the possible success rate of fertility treatments using GnRH therapy or gonadotropin therapy. Research is being carried out into the control mechanisms that lead to the control of GnRH from the hypothalamus and what external signals have an influence on the hypothalamus. This might in time lead to the development of medications that can restore the function of the hypothalamus, restore correct pulsatile GnRH release and “reverse” a case of Kallmann syndrome or CHH, which is known to happen in about 20% of cases at present.
On the 23rd March 2016 I had a phone interview for a late night radio show on local BBC radio. They had heard the interview on BBC Radio 2 and wanted to talk to me about Kallmann syndrome. It was a recorded interview rather than live this time.
This is a link to the radio show. The interview starts at about 1 hour 26 mins into the programme.
The link to the programme might not be active for very long. Hopefully this is a link to the audio file of the interview:
Recently I was on the Jeremy Vine show on BBC Radio 2 talking about Kallmann syndrome. It was only a brief interview but I tried to mention as many of the major points as I could. I was on the show as part of a segment on rare medical conditions with the show’s resident doctor, Dr Sarah Jarvis.
This is the link to the show. The interview starts at about 1 hour 9 mins into the show.
This link on the BBC website might only be active for a short time. He is a link to just the interview part:
There was so much else I could have talked about and it was a shame it was such a brief interview. However I am very grateful for the opportunity to raise awareness of the condition and am quite keen to do more in the future if I can.