The following information may help to address your question:
How is hypophosphatasia inherited?
Perinatal (onset before birth) and infantile hypophosphatasia (HPP) are inherited
in an autosomal recessive
This means that to be affected, a person must have a mutation
in both copies of the responsible gene
) in each cell
. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier
. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
- 25% (1 in 4) chance to be affected
- 50% (1 in 2) chance to be an unaffected carrier like each parent
- 25% chance to be unaffected and not be a carrier.
The milder forms, especially adult HPP and odontohypophosphatasia, may be inherited in an autosomal recessive or autosomal dominant
manner - depending on the effect the ALPL
mutation has on enzyme
In autosomal dominant inheritance, having a mutation in only one copy of the ALPL
gene in each cell is enough to cause features of the condition. When a person with a mutation that causes an autosomal dominant HPP has children, each child has a 50% (1 in 2) chance to inherit that mutation.
Most people with autosomal dominant HPP have inherited the mutation from a parent who may or may not have symptoms. Not all people with a mutation that causes autosomal dominant HPP develop symptoms of the condition. While it is possible to have autosomal dominant HPP due to a new mutation that was not inherited (a de novo
mutation), this has never been reported in HPP.
Last updated: 2/1/2016
Can the type or severity of hypophosphatasia vary among affected family members?
Yes. In general, the perinatal and infantile forms of hypophosphatasia (HPP) are inherited in an autosomal recessive
manner. The childhood form can be autosomal recessive or autosomal dominant
. The adult form and odontohypophosphatasia usually are autosomal dominant, but can also be inherited in an autosomal recessive manner.
However, significant variability among family members with HPP has been reported.
For example, one author reported a 15-month-old girl with symptoms suggestive of childhood HPP, who had a father with symptoms suggestive of odontohypophosphatasia, and a paternal aunt who died at 7 days old of apparent neonatal HPP.
HPP has shown reduced penetrance
. This means that not all people with a mutation that can cause autosomal dominant HPP will develop symptoms of HPP.
In families with recessive HPP, the severity of symptoms mostly has been reported to be comparable, or to differ only moderately, from one child to another. However, families with AR inheritance and larger variations among family members have been reported.
It is possible that other genetic, epigenetic
or environmental factors
may explain the clinical variability among families and between families with HPP. People with questions about potential risks to children or other family members are strongly encouraged to speak with a genetics professional to discuss family history
and what may be known about the specific mutation(s) in the family. The genetics of HPP is complex, so predicting how a person will be affected can be difficult.
Last updated: 2/1/2016
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Last updated: 12/6/2017
We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please
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