Re: Type I or type II? Recent developments.

November 11, 2005

Jeroen,

Thank you so much for posting this information on the board. I had

researched the gene mutation and pretty much came up with the same

facts. What I needed to hear from somone was that I needn't have

both of 's ovaries removed now to preserve her options later.

Of course may choose adoption, egg donation or freezing her

own tissue now for later conception. She feels she is too young to

understand the ramifications of all these options when she doesn't

even know the wishes of a father who isn't in the picture yet. I

was glad to hear that using hormone replacement therapy may not be

the horror that we are being told in the media. I am also worried

about radical treatments that the doctor's are proposing when the

technology is so new. What would really like to do is monitor

her ovarian activity by periodic blood tests and possible

ultrasounds. Even with the overwhelming incidences of POF in her

family, the experts claim that the severity of the symptons from

BPES can vary significantly from family memeber to family member.

Premature doesn't really have an age attached, it just means failure

prior to the average for all women. 's first doctor seemed a

little sugery happy. We have discussed the issue and we are going

to seek a physician that will take the least invasive tactic to

preserve her options. Thanks to all the members that have posted

messages telling me about your particular circumstance. It is

reassuring to hear of women who have at least one child. Good luck

to all of you. Hopefully infertility will not strike you or your

children but having the knowledge early in life will help you decide

the course of action to take.

's Mom

Kathy

>

> 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.

>

November 13, 2005

Dear Jeroen,

Thank you so much for the clarification. My daughter was tested by an endocronologist in New York City when she was two. They said she had healthy eggs. We thought we were in the clear, but we didn't know what to look for and the doctor was not familiar with the disease. I only understand now, that we need to test for POF not infertility. Now we will have to send our daughters blood to Belgium to be tested. She is only 4 now, but is it good to prepare and keep up to date on the latest developments.

I really appreciate your input.

Pam

November 14, 2005

Good to know, I will look into it.

November 14, 2005

Hi Kathy,

I'm glad to hear that you appreciated the information. I wish you

and all the best.

Jeroen

> >

> > 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.

> >

>

November 14, 2005

Hi Pam,

It's nice to hear that I clarified some things. Indeed it's not

infertility which has to be looked for but POF. However it's not

necessary to send a blood sample to Belgium. Most countries have a

specialized laboratory. In both Belgium and Holland for example,

there's one of such a laboratory. Only one because it's a rare

disorder so they send al the blood samples of the country to this

one laboratory (It would be to expensive for every laboratory to

have the testing material and almost never having to use it).

Belgium and Holland are both small countries so I can imagine that

in the U.S. there are more of these specialized laboratories.

Good luck to you.

Greetings,

Jeroen

>

> Dear Jeroen,

>

> Thank you so much for the clarification. My daughter was tested

by an

> endocronologist in New York City when she was two. They said she

had healthy eggs.

> We thought we were in the clear, but we didn't know what to look

for and the

> doctor was not familiar with the disease. I only understand now,

that we need

> to test for POF not infertility. Now we will have to send our

daughters

> blood to Belgium to be tested. She is only 4 now, but is it good

to prepare and

> keep up to date on the latest developments.

>

> I really appreciate your input.

>

> Pam

>

November 15, 2005

Thank you Jeroen for your recent medical information. I think I may

have started the recent discussions on infertility and POF. I'm

( they are a few sarah's on this site so I'll say D, I'm

28 years old and was planning to have children in a few years after

travelling a little more. I was surfing the web about whether i

could pass BPES onto any children and found out 50% chance but also

found this group, which has been a great source of comfort as I do

not know anyone else with BPES and infact only found out the correct

term from this group and checking medical records two weeks ago. My

parents had only ever been told it was ptosis. I have now been

referred to the research centre in Newcastle Upon Tyne to find out

about POF but this could take two to three months for an

appointment.

I would like to say hi to Clare and her daughter Emy, who live in

the UK, you were the first to welcome me to the group and I was so

touched my your comforting words about having children and passing

BPES onto any children. I feel very positive about having children

of my own now after reading everyones comments and looking at all

the beautiful children in the photos and I'm not worried any longer

about having a child with BPES as he or she will be just like me. I

continue to live in hope that I can have a child.

Take care to everyone,

D