Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group What are the chances...?

Hi...

Does anyone know the scientific percentage of hereditary probability? We have a one year old son. I've heard conflicting stories as to the statistical probability of him having it also. I've heard anywhere between 10-50%- noting that firstborns are more likely to have it.

Can anyone else say with more certainty? I have thought about getting him DNA tested... but we agreed we'd rather not know or put him in a position to know. If that makes any sense.

My husband's father died of AS (it attacked his heart), my husband Caleb has AS and so does his only sibling, a younger sister. I've thought about it and it just doesn't sound like very good odds to me! Of course that terrifies me to think of our precious child going through this pain. No parent wants their child to be in pain.

What has proved true for your families? Do your parents, siblings, children have this disease?

So glad to be here!!!
janae

The good news is children are statistically most likely to have a disease free life.

Patterns of inheritance have been for AS have been studied. This is the way I understand it. The chance of inheritance varies depending on if you are (1)HLAB27positive or negative-; (2) if you are from a family with others affected, (especially if there are any female relatives with AS); (3) if you have associated inflammatory bowel disease such as ulcerative colitis.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10568571&dopt=Abstract
Calin A, Brophy S, Blake D.
Impact of sex on inheritance of ankylosing spondylitis: a cohort study.
Lancet. 1999 Nov 13;354(9191):1687-90.
PMID: 10568571

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11053066&dopt=Abstract
Brown MA, Laval SH, Brophy S, Calin A.
Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis.
Ann Rheum Dis. 2000 Nov;59(11):883-6.
PMID: 11053066
"RESULTS: The recurrence risks in different degrees of relatives were: monozygotic (MZ) twins 63% (17/27), first degree relatives 8.2% (441/5390), second degree relatives 1.0% (8/834), and third degree relatives 0. 7% (7/997). Parent-child recurrence risk (7.9%, 37/466) was not significantly different from the sibling recurrence risk (8.2%, 404/4924), excluding a significant dominance genetic component to susceptibility."

Here is my understanding (based on the Lancet article above mostly):
For relatives of B27 women with AS, the chance of children having AS is highest, on the order of 40% according to the Lancet article cited above, so if you come from a family with both men and women affected, that would be a higher risk family.

Families with only men affected, or with no one else affected, have lower risk, the children of B27 men in this kind of family is on the order of 8%. Assuming that the father has only one copy of the B27 gene and the mother doesn’t carry the B27 gene, which would be the usual case, statistically 50% of children would be B27 , therefore the risk of a B27 child for developing the disease would be on the order of 16%. This means that any child would have a 92% chance of being without disease, and any B27 child would have a 84% chance of being without disease. The odds would be greatly in your favor of having a disease free child.

If you are B27 negative, without associated bowel disease, these are often isolated sporadic cases. If you have a sporadic B27 negative case without bowel disease, your child would have very low risk of disease.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6232703&dopt=Abstract

If you are B27 negative with associated bowel disease, then there could be familial inheritance, and your child would have some risk (I don’t know of a calculated numerical value for that risk).
Information on inheritance patterns in B27 negative cases:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=107868&dopt=Abstract

Recently, an association of HLAB35 with patient with spondyloarthropathy associated with inflammatory bowel disease [enteropathic arthritis] has been found:

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10857795&dopt=Abstract
Said-Nahal R, Miceli-Richard C, Berthelot JM, Duche A, Dernis-Labous E, Le
Blevec G, Saraux A, Perdriger A, Guis S, Claudepierre P, Sibilia J, Amor B,
Dougados M, Breban M.
The familial form of spondylarthropathy: a clinical study of 115 multiplex
families. Groupe Francais d'Etude Genetique des Spondylarthropathies.
Arthritis Rheum. 2000 Jun;43(6):1356-65.
PMID: 10857795; UI: 20313938
"… Inflammatory bowel disease and HLA-B35 were overrepresented in the 7 families containing HLA-B27-negative patients."

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10648455&dopt=Abstract
Orchard TR, Thiyagaraja S, Welsh KI, Wordsworth BP, Hill Gaston JS, Jewell DP.
Clinical phenotype is related to HLA genotype in the peripheral arthropathies of
inflammatory bowel disease.
Gastroenterology. 2000 Feb;118(2):274-8.
PMID: 10648455; UI: 20115501
"… RESULTS: Type 1 arthropathy [IBD associated arthropathy with a pattern of joint involvement consistent with spondyloarthropathy] was associated with HLA-DRB1*0103 (DR103; a rare subtype of DR1) in 33% (P < 0.0001; relative risk [RR], 12.1), B*35 in 30% (P = 0.01; RR, 2.2), and B*27 in 26% (P = 0. 001; RR, 4.0).

Edited by Evelyn on 04/08/02 10:41 AM (server time).

I have four son's None of them have developed symptoms of the diease. Range in age 28 to 19. Although I did not know what I had by the time I had reached their age I had many of the symptoms. 10% of the population carry the gene 3% of those develop AS.

Birth order and risk for AS:

the following report introduced this question:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11145041&dopt=Abstract
Baudoin P, van der Horst-Bruinsma IE, Dekker-Saeys AJ, Weinreich S, Bezemer
PD, Dijkmans BA.
Increased risk of developing ankylosing spondylitis among first-born children.
Arthritis Rheum. 2000 Dec;43(12):2818-22.
PMID: 11145041
"RESULTS: The number of first-born children with AS was significantly higher than would be expected in case of an equal risk between first-born and later-born children (26 versus 20 for families with 2 children [P = 0.029] and 63 versus 47.6 for all families [P = 0.004])… CONCLUSION: Low birth order is a risk factor for AS in humans."

This recent analysis of a larger patient pool suggests there is NO increased risk based on birth order:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11908567&dopt=Abstract
Brophy S, Taylor G, Calin A.
Birth order and ankylosing spondylitis: no increased risk of developing
ankylosing spondylitis among first-born children.
J Rheumatol. 2002 Mar;29(3):527-9.
PMID: 11908567
"CONCLUSION: There was no statistically significant effect of birth order based on our data. Findings suggesting a birth order effect may be skewed, as it is possible that those parents who do have AS will be less likely to have a large family and yet it is their offspring who will be at greatest risk of developing disease. This will affect the data, as those children born into a large family (i.e., high birth order children) will be at a lower risk of AS than any child born into a small but family-history-positive unit."

Edited by Evelyn on 04/08/02 10:45 AM (server time).

Dear Smed, other genes that relatives share with each other IN ADDITION to HLAB27 result in increased risk for B27 positive close relatives of people with AS over and above the risk in the general HLA B27 positive population

http://www.emedicine.com/med/topic2700.htm
Approximately 1-2% of all people who are positive for HLA-B27 develop AS. This increases to 15-20% if they have a first-degree relative with AS.

Edited by Evelyn on 04/08/02 11:41 AM (server time).

Hi Janae

As you can see Evelyn's answers are wonderfully comprehensive. I wrestled with my fear of AS for my children but not much I can do about it.

My maternal grandmother had AS and it was brutally bad case. My mother has it also. I am the child on my tier of that family tree that has it. No other sibling or cousin has it. Me being one of 8 on that tier made my personal odds of having AS 12.5%.


stevec-they also serve who stand and wait

Hi janae;
I was diagnosed in mid january of this year and my rheumy told me it was highly likely that my children ( I have two) would/could have AS. I worried about this and read a lot, but finally decided that I would NOT have them tested as yet. At least not until I have some reason to believe they may be developing AS. I now know that the risk is very small and so why burden them with the awful thought that every ache or pain could be a chronic debilitating disease? So, for now, just watching....
BTW, I am the only person in my family that has been diagnosed. My sister has some hip complaints and she is planning on getting tested sometime soon. I am not aware of any AS in my family background.
Darla

"Starting today, your kindness will lead you to success" from a recent fortune cookie

Evelyn's post has great information. But I wouldn't worry. If your child would develop symptoms, then is soon enough to worry. And you'll know, it won't be years and years of pain that no one knows what it is. Neither of my parents had AS, nor any of their sibs. But my paternal grandmother and maternal grandfather may have had AS. Among my sibs, 2 out of 5 have been dx'd with AS, the oldest and the youngest girls. And there is a possibility that a brother has it, too. But I'm still not overly concerned about my children. I figure it will be a bridge that we will cross when we come to it. Odds are about the same that they will get run over by a train.


Hugs,

Cindy

My family was hit pretty hard with AS which came down through my mother's side of the family. Looking at five complete generations on her side of the family, one of every three relatives has/had developed AS.

My biggest wish is that the statistics will not get any worse. My biggest fear is that they probably could.

George

Breb Assyl

Janae,
I don't know the breakdowns of statistics for this. In my family there are 10 of us kids. 3 have been diagnosed with AS. ( my oldest brother, 30 years ago at the age 14, my sister last year.. and myself this year) Two other brothers have similar problems as the three of us do, but have not been tested. I also worry about my two boys (13 and 5) I am hoping that some day with all of the new studies that seem to be cropping up, that they will come up with something so all of our children and their children will never have to worry about dealing with this disease.

Take care,

Pam

"Just like moons and like suns, with the certainty of tides. Just like hopes springing high, Still I'll rise." Maya Angelou