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Thread: Nw article in Cell on spontaneous congenital scoliosis

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    Nw article in Cell on spontaneous congenital scoliosis

    A Mechanism for Gene-Environment Interaction in the Etiology of Congenital Scoliosis

    Cell is a huge journal. I was there looking for a different article and came acorss this.

    Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.
    Last edited by Kevin_Mc; 04-25-2012 at 06:10 PM.

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    And then me might wonder if the tendency to allow sporadic hypoxia in the womb is itself under some genetic control.

    I'm not sure what they think causes transient hypoxia in human (absent choking someone I guess).
    Sharon, mother of identical twin girls with scoliosis

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    Quote Originally Posted by Kevin_Mc View Post
    A Mechanism for Gene-Environment Interaction in the Etiology of Congenital Scoliosis

    "Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction."
    During PGV, Tamzin scoliosis because apparent, swiftly. She had just had her pre-pubescent growth spurt. When first noticed something amiss when she because breathless doing a tempo session on the track. Tamzin's LT at this speed had been excellent all year, now uncharacteristic breathlessness. I.e., hypoxia. This girl trained hard; really hard. With her strength, it quite possible that the hypoxia teamed up with a genetic risk factor and rapidly worsened insidious scoloisis?


    Quote Originally Posted by Pooka
    I'm not sure what they think causes transient hypoxia in human (absent choking someone I guess).
    Running, Sharon, would be one cause.
    07/11: (10yrs) T40, L39, pelvic tilt, rotation T15 & L11
    11/11: Chiari 1 & syrinx, T35, L27, pelvis 0
    05/12: (11yrs) stopped brace, assessed T&L 25 - 30...>14lbs , >8 cm
    12/12: < 25 LC & TC, >14 cms, >20 lbs, neuro symptoms abated, but are there
    05/13: (12yrs) <25, >22cms height, puberty a year ago

    Avoid 'faith' in 'experts'. “In consequence of this error many persons pass for normal, and indeed for highly valuable members of society, who are incurably mad...”

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    Quote Originally Posted by TAMZTOM View Post
    During PGV, Tamzin scoliosis because apparent, swiftly. She had just had her pre-pubescent growth spurt. When first noticed something amiss when she because breathless doing a tempo session on the track. Tamzin's LT at this speed had been excellent all year, now uncharacteristic breathlessness. I.e., hypoxia. This girl trained hard; really hard. With her strength, it quite possible that the hypoxia teamed up with a genetic risk factor and rapidly worsened insidious scoloisis?
    Tom, this article has to do with congenital scoliosis (malformed vertebra) being triggered in the womb by hypoxia during critical periods of vertebral body formation. It has zero to do with idiopathic scoliosis because that doesn't involve malformed vertebra. It also has zero to do with issues after gestation ends.

    Running, Sharon, would be one cause.
    So then pregnant mothers should NOT run!

    They should look for whether women who run and train hard during pregnancy have more kids with congenital scoliosis. That would be a test.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
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    Quote Originally Posted by hdugger View Post
    I think it's only not having oxygen during critical gestational periods - I don't it matters after the child is born.
    Got it, thanks for reminding me that my brain shut off hours ago.

    Quote Originally Posted by SHARON
    So then pregnant mothers should NOT run! They should look for whether women who run and train hard during pregnancy have more kids with congenital scoliosis. That would be a test.
    Just to debate that...cos such mental activity is a drug :-(...that the mother was knackered doesn't necessitate the baby snuggler being deprived of oxygen. I though the little buggers were first in the queue for everything, food, oxygen, etc...it's the pregnant mother who starve.

    Night. I'm rambling.
    07/11: (10yrs) T40, L39, pelvic tilt, rotation T15 & L11
    11/11: Chiari 1 & syrinx, T35, L27, pelvis 0
    05/12: (11yrs) stopped brace, assessed T&L 25 - 30...>14lbs , >8 cm
    12/12: < 25 LC & TC, >14 cms, >20 lbs, neuro symptoms abated, but are there
    05/13: (12yrs) <25, >22cms height, puberty a year ago

    Avoid 'faith' in 'experts'. “In consequence of this error many persons pass for normal, and indeed for highly valuable members of society, who are incurably mad...”

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    Quote Originally Posted by Pooka1 View Post
    And then me might wonder if the tendency to allow sporadic hypoxia in the womb is itself under some genetic control.

    I'm not sure what they think causes transient hypoxia in human (absent choking someone I guess).
    I haven't read the other posts yet, but I'm wondering if maternal smoking would contribute to this in a predisposed embryo. Some of the stuff I've read about what happens to an embryo/fetus when a mother takes a drag off of a cigarette is just shockingly scary.
    Last edited by rohrer01; 04-28-2012 at 11:39 PM. Reason: bad grammar
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    Quote Originally Posted by TAMZTOM View Post
    Just to debate that...cos such mental activity is a drug :-(...that the mother was knackered doesn't necessitate the baby snuggler being deprived of oxygen. I though the little buggers were first in the queue for everything, food, oxygen, etc...it's the pregnant mother who starve.
    That might work for nutrients because the mother's body can start breaking down muscle or even organ tissue to deliver nutrients to the fetus. But it can't work for oxygen because there is no way for her body to make it. The only source of oxygen is the atmosphere. And the body has no mechanism to store oxygen.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
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    "We are all African."

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    Quote Originally Posted by Pooka1 View Post
    That might work for nutrients because the mother's body can start breaking down muscle or even organ tissue to deliver nutrients to the fetus. But it can't work for oxygen because there is no way for her body to make it. The only source of oxygen is the atmosphere. And the body has no mechanism to store oxygen.
    I think that's probably correct, as I've never heard of a decrease in the amount of congenital scoliosis in recent years. In the 1940's, 50's, and 60's, a lot of women in the U.S. smoked throughout their pregnancies.

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    Quote Originally Posted by LindaRacine View Post
    I think that's probably correct, as I've never heard of a decrease in the amount of congenital scoliosis in recent years. In the 1940's, 50's, and 60's, a lot of women in the U.S. smoked throughout their pregnancies.

    --Linda
    Yes that's a good point. If hypoxia goes up with smoking, and less women smoke, then the rate of congenital cases should be less now compared to a few decades ago. I don't know if anyone is tracking that.

    I am still back to wondering what could cause transient hypoxia in the womb? If it isn't smoking and it isn't running (two of the most obvious candidates) then it must be something about the woman's physiology which fails to deliver the oxygen. That sounds like straight genetics to me. And it needn't necessarily show understandable inheritance patterns if it is a spontaneous mutation. Identical twinning is considered to be a spontaneous mutation of a type and actually a birth defect by some. Or it might just be due to a complex pattern of inheritance like idiopathic scoliosis which is considered polygenetic and multifactorial. I wonder what the prevalence and incidence is of congenital scoliosis versus something like identical twinning. The rate of identical twinning is very stable worldwide and through time as far as I know. I wonder if congenital scoliosis is also.

    Like the prominent scoliosis researcher, Jack Cheng states, "It's all genetics."
    Last edited by Pooka1; 04-29-2012 at 04:56 PM.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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