This subject has come up from time to time in this group... and I thought this

abstract was interesting.. suggesting that there is some proof to back up the

thoughts of increased severity...



NOTE: Just because this study was done on 1A, it doesn't mean that it is limited

to only 1A... just that 1A was the sub-type that was subject of this study..



Anyone here find that later generations are affected more severely?







http://www.ncbi.nlm.nih.gov/pubmed/18438698?ordinalpos=1&itool=EntrezSystem2.PEn\

trez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpo\

s=3&log$=relatedarticles&logdbfrom=pubmed





: J Neurol. 2008 Jun;255(6):813-9. Epub 2008 Apr 30



Increased severity over generations of Charcot-Marie-Tooth disease type 1A.

Steiner I, Gotkine M, Steiner-Birmanns B, Biran I, Silverstein S, Abeliovich D,

Argov Z, Wirguin I.

Neurological Sciences Unit, Hadassah University Hospital, Mount Scopus, 24035,

Jerusalem 91240, Israel. isteiner@...



BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant

polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2,

containing the PMP22 gene. This mutation is not modified during inheritance.



OBJECTIVES: We set forth to test the hypothesis that in a subgroup of CMT1A

patients there is clinical anticipation, namely an increase in disease severity

over generations.



METHODS: Thirty-nine CMT1A mutation-positive patients in 16 families and 23

parent-offspring pairs were evaluated. This included 14 families with 2

generations and 2 families with 3 generations. Age of presentation was assessed

by interviewing the patients and clinical severity was measured using the CMT

neuropathy score (CMTNS).



RESULTS: In 21/23 parent-child pairs and 14/16 families, there was an earlier

age of presentation in children of genetically affected parents. The mean age of

onset in the progeny was 12.61 years compared to 41.22 years in the parent

generation, (p < 0.001).Mean severity in the younger generation was slightly

higher than that of the parent generation. When corrected for the age

difference, the trend for a worse phenotype in the younger generation became

statistically significant (p < 0.02,Wilcoxon signed rank test).



CONCLUSIONS: Our findings suggest that in a subgroup of CMT1A patients there is

an increase in clinical severity over generations. The mechanism responsible for

this observation remains unknown. Our findings should be validated on a larger

cohort of CMT1A families.



PMID: 18438698 [PubMed - indexed for MEDLINE





[Non-text portions of this message have been removed]

Not me and not my Mom, etc. Ernie.  Thanks for the sites.



Sal



>

> Anyone here find that later generations are affected more severely?

>

>

>

-you know i am new to this site. i just join another one too. but any

ways, my whole family has it cmt 1a and my sister's daughter and my son

have it worse than us. i was wondering the same thing. but my brothers

child do not have it worse than him.

now my aunts sons have it worse than them, so is it the woman's child have it

worse than the men's child???



but i do have it worse than my dad did.















-- In CMT-Support@yahoogroups.com, "sal2491" <gbsb2002@...> wrote:

>

> Not me and not my Mom, etc. Ernie.  Thanks for the sites.

>

> Sal

>

> >

> > Anyone here find that later generations are affected more severely?

> >

> >

> >

>

Hi,  I don't believe that a woman's child has it worse than a man's child...



Sal



--- In CMT-Support@yahoogroups.com, "tmkwek56" <tkwek@...> wrote:

>

> -you know i am new to this site. i just join another one too. but any

> ways, my whole family has it cmt 1a and my sister's daughter and my son

> have it worse than us. i was wondering the same thing. but my brothers

> child do not have it worse than him.

> now my aunts sons have it worse than them, so is it the woman's child have it

worse than the men's child???

>

> but i do have it worse than my dad did.

>

>

>

>

>

>

>

> -- In CMT-Support@yahoogroups.com, "sal2491" <gbsb2002@> wrote:

> >

> > Not me and not my Mom, etc. Ernie.  Thanks for the sites.

> >

> > Sal

> >

> > >

> > > Anyone here find that later generations are affected more severely?

> > >

> > >

> > >

> >

>

In my opinion Sal, the study was done on too small a base group to be really

useful... but they have to start somewhere with these ideas and theory's.



In our case, there are family 'stories' of my great grandmother being stuck

in bed or a chair from her mid 30's till she passed (but nothing known about

CMT back then)... My mother was worse off than her dad at any given age.. I

am farther progressed than my mom was at any given age.  My youngest son is

farther progressed than I was at his age, but his older sister (not

confirmed yet) is much more mildly affected.. Hard to tell she has it if you

didn't know what you were looking for..  Her daughter (again, not confirmed

but should be changing that situation later this year or early next), is in

pretty bad shape already.  She can barely walk with out AFO's, hip

dysplasia, gross and fine motor delays and she is only 2...



It will be interesting to hear what others have to report on the subject..



In any case, thanks for the reply... Hope you have a great weekend my

friend..



Ernie









----- Original Message -----

From: "sal2491" <gbsb2002@...>

To: <CMT-Support@yahoogroups.com>

Sent: Friday, July 03, 2009 5:58 PM

Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A





Not me and not my Mom, etc. Ernie.  Thanks for the sites.



Sal



>

> Anyone here find that later generations are affected more severely?

>

>

>







------------------------------------



Group Owners:   CMT-Support-owner@yahoogroups.com







Yahoo! Groups Links

Hi Ernie,



I'm sure everyone's family is different.  So we only go by what is happening in

our own family.  It will be interesting as we are always learning.  Have a great

weekend!



Sal



--- In CMT-Support@yahoogroups.com, "Ernie's Mail" <EZgoing2@...> wrote:

>

> In my opinion Sal, the study was done on too small a base group to be really

> useful... but they have to start somewhere with these ideas and theory's.

>

> In our case, there are family 'stories' of my great grandmother being stuck

> in bed or a chair from her mid 30's till she passed (but nothing known about

> CMT back then)... My mother was worse off than her dad at any given age.. I

> am farther progressed than my mom was at any given age.  My youngest son is

> farther progressed than I was at his age, but his older sister (not

> confirmed yet) is much more mildly affected.. Hard to tell she has it if you

> didn't know what you were looking for..  Her daughter (again, not confirmed

> but should be changing that situation later this year or early next), is in

> pretty bad shape already.  She can barely walk with out AFO's, hip

> dysplasia, gross and fine motor delays and she is only 2...

>

> It will be interesting to hear what others have to report on the subject..

>

> In any case, thanks for the reply... Hope you have a great weekend my

> friend..

>

> Ernie

>

>

>

>

> ----- Original Message -----

> From: "sal2491" <gbsb2002@...>

> To: <CMT-Support@yahoogroups.com>

> Sent: Friday, July 03, 2009 5:58 PM

> Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A

>

>

> Not me and not my Mom, etc. Ernie.  Thanks for the sites.

>

> Sal

>

> >

> > Anyone here find that later generations are affected more severely?

> >

> >

> >

>

>

>

> ------------------------------------

>

> Group Owners:   CMT-Support-owner@yahoogroups.com

>

>

>

> Yahoo! Groups Links

>

Hi, Ernie and Sal, both my father and I have RLS with our CMT2.  It was

diagnosed in sleep studies.

lj



--- On Fri, 7/3/09, sal2491 <gbsb2002@...> wrote:





From: sal2491 <gbsb2002@...>

Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A

To: CMT-Support@yahoogroups.com

Date: Friday, July 3, 2009, 5:58 PM

















Not me and not my Mom, etc. Ernie. Thanks for the sites.



Sal



>

> Anyone here find that later generations are affected more severely?

>

>

>







































[Non-text portions of this message have been removed]

I think RLS is more prevalent in CMT Type 2's.  Although it can certainly be in

other types as well.



Sal



--- In CMT-Support@yahoogroups.com, Lana Jarvis <fyfer1949@...> wrote:

>

> Hi, Ernie and Sal, both my father and I have RLS with our CMT2.  It was

diagnosed in sleep studies.

> lj

>

> --- On Fri, 7/3/09, sal2491 <gbsb2002@...> wrote:

>

>

> From: sal2491 <gbsb2002@...>

> Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A

> To: CMT-Support@yahoogroups.com

> Date: Friday, July 3, 2009, 5:58 PM

>

>

>

>

>

>

>

>

> Not me and not my Mom, etc. Ernie. Thanks for the sites.

>

> Sal

>

> >

> > Anyone here find that later generations are affected more severely?

> >

> >

> >

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

> [Non-text portions of this message have been removed]

>

>

> >

> > Anyone here find that later generations are affected more severely?

> >

=



In 3 generations,  I am the end of the line it appears and I definitely have

more severe complications than my mother and her mother, her mother's sister and

the generation before them

I'm SO happy for you, Lcq!

 

Does this mean that none of your descendents have it?  I think that's what you

meant..

lj



--- On Sat, 7/18/09, dcq_ilme <dcq_ilme@...> wrote:





From: dcq_ilme <dcq_ilme@...>

Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A

To: CMT-Support@yahoogroups.com

Date: Saturday, July 18, 2009, 4:46 PM





 









>

> >

> > Anyone here find that later generations are affected more severely?

> >

=



In 3 generations, I am the end of the line it appears and I definitely have more

severe complications than my mother and her mother, her mother's sister and the

generation before them







































[Non-text portions of this message have been removed]

My condition is as bad or worse as my 85yo father.  I'm 59.

lj



--- On Fri, 7/3/09, Ernie's Mail <EZgoing2@...> wrote:





From: Ernie's Mail <EZgoing2@...>

Subject: Re: [CMT-Support] Re: Increased severity over generations of CMT 1A

To: CMT-Support@yahoogroups.com

Date: Friday, July 3, 2009, 9:35 PM

















In my opinion Sal, the study was done on too small a base group to be really

useful... but they have to start somewhere with these ideas and theory's.



In our case, there are family 'stories' of my great grandmother being stuck

in bed or a chair from her mid 30's till she passed (but nothing known about

CMT back then)... My mother was worse off than her dad at any given age.. I

am farther progressed than my mom was at any given age. My youngest son is

farther progressed than I was at his age, but his older sister (not

confirmed yet) is much more mildly affected.. Hard to tell she has it if you

didn't know what you were looking for.. Her daughter (again, not confirmed

but should be changing that situation later this year or early next), is in

pretty bad shape already. She can barely walk with out AFO's, hip

dysplasia, gross and fine motor delays and she is only 2...



It will be interesting to hear what others have to report on the subject..



In any case, thanks for the reply... Hope you have a great weekend my

friend..



Ernie



----- Original Message -----

From: "sal2491" <gbsb2002@yahoo. com>

To: <CMT-Support@ yahoogroups. com>

Sent: Friday, July 03, 2009 5:58 PM

Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A



Not me and not my Mom, etc. Ernie. Thanks for the sites.



Sal



>

> Anyone here find that later generations are affected more severely?

>

>

>



------------ --------- --------- ------



Group Owners: CMT-Support- owner@yahoogroup s.com



Yahoo! Groups Links







































[Non-text portions of this message have been removed]

My mother is 68 and is just now experiencing the problems I was having at 36

yrs of age.  My son is 19 and he is having bad problems already.  So I have

noticed that, in my family, each generation seems to be effected at an

earlier age but I know that each case is different.



-------Original Message-------



From: Lana Jarvis

Date: 7/11/2009 3:47:32 PM

To: CMT-Support@yahoogroups.com

Subject: Re: [CMT-Support] Re: Increased severity over generations of CMT 1A









My condition is as bad or worse as my 85yo father.  I'm 59.

lj



--- On Fri, 7/3/09, Ernie's Mail <EZgoing2@...> wrote:



From: Ernie's Mail <EZgoing2@...>

Subject: Re: [CMT-Support] Re: Increased severity over generations of CMT 1A

To: CMT-Support@yahoogroups.com

Date: Friday, July 3, 2009, 9:35 PM



In my opinion Sal, the study was done on too small a base group to be really



useful... but they have to start somewhere with these ideas and theory's.



In our case, there are family 'stories' of my great grandmother being stuck

in bed or a chair from her mid 30's till she passed (but nothing known about



CMT back then)... My mother was worse off than her dad at any given age.. I

am farther progressed than my mom was at any given age. My youngest son is

farther progressed than I was at his age, but his older sister (not

confirmed yet) is much more mildly affected.. Hard to tell she has it if you



didn't know what you were looking for.. Her daughter (again, not confirmed

but should be changing that situation later this year or early next), is in

pretty bad shape already. She can barely walk with out AFO's, hip

dysplasia, gross and fine motor delays and she is only 2...



It will be interesting to hear what others have to report on the subject..



In any case, thanks for the reply... Hope you have a great weekend my

friend..



Ernie



----- Original Message -----

From: "sal2491" <gbsb2002@yahoo. com>

To: <CMT-Support@ yahoogroups. com>

Sent: Friday, July 03, 2009 5:58 PM

Subject: [CMT-Support] Re: Increased severity over generations of CMT 1A



Not me and not my Mom, etc. Ernie. Thanks for the sites.



Sal



>

> Anyone here find that later generations are affected more severely?

>

>

>



------------ --------- --------- ------



Group Owners: CMT-Support- owner@yahoogroup s.com



Yahoo! Groups Links



[Non-text portions of this message have been removed]











[Non-text portions of this message have been removed]