For new people who have recently joined the group in the past 4 months.

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Hi to all the new people in the group.Just over a year ago Jeroen - who has a degree in medicine - posted thismessage in connection with a strand of conversation.It is very nicely written and easy to understand - so I thought I would postit again so that new people in the group can benefit from it.RegardsShireen MohandesLondon, England> Sent: 11 November 2005 14:13> blepharophimosis > Subject: blepharophimosis Type I or type II? Recent developments.> > Hi everybody,> > I read the recent posts about type I and type II BPES and > infertility. I noticed that there are a lot of questions and > uncertainties. Maybe I can clarify one and other. I have a > degree in medicine and although I am now specializing in > psychiatry, I am familiar with general medicine matters. > Moreover, recently I spoke with Dr. Debaere, who's a world > expert on genetic research in BPES.> > First I'd like to explain something about genetics. Humans > have 46 chromosomes. We have 2 Sex chromosomes, XX (female) > or XY (male), and 44 autosomal chromosomes. Each parent > Passes 23 chromosomes (22 autosomal and 1 sex chromosome) so > you get 23 chromosome "couples". > Chromosomes consist of DNA. Specific regions on chromosomes > are called genes. There are a lot of genes (eye-colour, > hair-colour, ... > etc). In our cells there is a sophisticated system that can > translate the information which is encoded in the DNA, the > building material of genes, and form proteins. So a gene > actually stands for a specific protein (like there is a gene > for insulin). How do genetic disorders arise? Genetic > disorders arise when there is a mutation (change) in the DNA > within a specific gene region. This alters the gene and, > thus, alters the protein which is formed. This is important. > For example insulin which is different from normal insulin > might not be able to lower blood sugar levels. Once a genetic > disorder has arisen, which can happen spontaneously, it can > be passed from parents to children. Genetic disorders can be > "dominant" or "recessive". When a genetic disorder is > dominant only one of the two genes in the gene couple (the > one from father or the one from mother) has to be altered to > give rise to the disorder. > When a genetic disorder is recessive both the father and the > mother need to pass an altered gene to give rise to the disorder.> > What about BPES? BPES is an autosomal dominant genetic > disorder. The gene is called FOXL2 and is located on > chromosome 3. Chromosome 3 is an autosomal chromosome and the > fact that the disorder is dominant means that you only need > to have one altered gene to get the disorder. The different > types (I and II) of BPES were first described in 1983 > (Zlotogora). Type I includes the four major features > (blepharophimosis, ptosis, epicanthus inversus and> telecanthus) and female infertility caused by premature > ovarian failure (POF). Type II includes only the four major > features. The difference between Type I and II is the > position on which the DNA, and thus the gene, is mutated > (altered). There are several (at least> 21) known mutations of the FOXL2 gene. Depending on the > location these mutations give rise to a shortened protein or > an extended protein. The ones that give rise to a shortened > protein cause type I and the ones that give rise to an > extended protein cause type II. > For some mutations it's not clear which type they cause. > During a genetic investigation, which takes about three > months, they try to find a known mutation to see if they are > able to tell which type of BPES the affected person has.> > What about the management of POF? Management of POF needs to > address the two major medical issues: hormone replacement > therapy (HRT) and infertility. > > HRT: Oestrogen and progesterone replacement therapy is > usually indicated. No comparative data are available to guide > estrogen use in young women as most studies on HRT involve > post-menopausal women, but the advantages often outweigh the > possible side-effects.> > Infertility: No effective treatment for infertility exists. > Adoption and oocyte (egg) donation are among the available > options. However, more recently there are some new therapies > under investigation. > Ovarian tissue and oocyte cryopreservation (freezing in) hold > promise for fertility preservation in the women most likely > to undergo ovarian failure. Adolescent girls with BPES who > have a risk of developing POF could be candidates for ovarian > (not necessarily the complete ovary so it's not necessary to > cause surgical> menopause) cryopreservation. This cryopreserved ovarian > tissue can be used in two ways: retransplanting and in vitro > stimulation. The first live birth after retransplantation was > reported in 2004 (this was not a woman with BPES). Note that > these techniques are not (yet) applied on a large scale. > Women with POF often reach menopause when they are 25-30 years old. > In the old days, when women conceived at a younger age, this > was not necessarily a problem. Nowadays most women start a > career and think of children at an older age which makes POF > more of an issue. > Endocrinologic and gynecologic follow-up are advised in > affected females in whom the BPES type is unknown or in whom > BPES type I is suspected based on a positive family history > or suggestive FOXL2 mutation.> > I myself had a blood sample taken one and a half month ago. > We are planning to have more kids and we just want to know > which type I have to be as prepared ad possible. I do not > have the result yet. It takes about three months.> > I hope I was of any help. If some things are unclear please > ask questions.> > Greetings,> Jeroen.__