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Author Topic: How is XLH inherited?  (Read 3627 times)


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How is XLH inherited?
« on: January 24, 2015, 08:58:33 PM »
Technically, XLH refers to hypophosphatemia that is "X-linked" (i.e., the relevant genetic defect is on the X chromosome), and the genetic transmission is explained below. Note, however, that "autosomal dominant" version (the relevant genetic defect may not be on the X chromosome) is informally referred to as XLH, but the genetic transmission is slightly different. The only way to know for sure which version a patient has is through genetic testing. Whether the defect is on the X chromosome or elsewhere does not appear to affect the symptomatology, although there is no scientific research on the topic.

There's a good explanation of the genetic transmission of x-linked conditions (both dominant and recessive; keep in mind that XLH is a DOMINANT condition) here (and click on the illustrations if you're a visual learner): http://ghr.nlm.nih.gov/handbook/inheritance/inheritancepatterns

You can find information about autosomal transmission there as well. Again, it is believed that in MOST autosomal cases, the condition is DOMINANT, although a vanishingly small number of RECESSIVE cases have been identified.

A genetics counselor explained how XLH is transmitted at West Coast XLH Day in 2015. Here's the video of that presentation:

The simple version (for true XLH) is:

A woman has a 50/50 chance of transmitting the defective gene to each of her children, who will then have XLH. If she has four children, regardless of their gender, the odds are that two would have XLH and two would not. (Of course, that's just a statistical average, and actual outcomes may be different.)

A man will transmit the defective gene to ALL of his DAUGHTERS ONLY (and none of his sons). Thus, if he has four children, and two are girls and two are boys, then both girls will have XLH and neither boy will have XLH.

The gender of the child shouldn't matter for autosomal cases, so a father with autosomal hypophosphatemia may have a daughter withOUT XLH.

One frequently repeated myth is that someone can be a "carrier" for XLH without having the condition him/herself. That is only true of recessive conditions, and XLH (including most autosomal versions) are DOMINANT. That means that if the person has the genetic defect, and is capable of passing it on to the next generation, he/she will also have hypophosphatemia.

This misconception arises from two common situations with XLH:
1. the symptoms are variable, so a mildly affected parent (especially women who tend to have less severe symptoms at least during childhood and early adulthood) may not be aware he/she has it until his/her child is diagnosed with XLH and doctors then check the parents' blood levels for phosphorus wasting.

2. A substantial number of XLH patients are "spontaneous" cases. This just means that the defect first occurred in that patient's DNA during conception, much like any birth defect happens. There's a natural, human tendency to want to explain the spontaneous mutation, to look for someone in the family who might have had been a carrier. Unless that person was one of the patient's parents (see the first example of an undiagnosed case) who simply hadn't been diagnosed, there won't be an answer. The mutation is simply a random event. Neither parent has XLH and neither parent is a carrier. The child simply has a new, or "spontaneous" mutation, just as somewhere in genetic history there was a spontaneous mutation that led to generations of XLH patients, and the children of the spontaneous XLH patient will inherit in the pattern described above.
« Last Edit: February 02, 2016, 06:39:04 PM by GinJones »