Mutated gene frequency for autosomal recessive disorders is estimated by calculating the square root of the disease frequency. Considering that Crigler-Najjar disease occurs in 1 in 1,000000, the altered gene frequency is 1:1000. Therefore, the frequency of unaffected persons carrying the mutated UGT1A1 gene (defined as carrier or heterozygote) is 1:500, since we have two copies of each autosomal gene. Carriers for a mutation in the Crigler-Najjar syndrome gene have about half the UGT1A1 enzyme activity of a normal adult. Despite that, since along with the mutated copy they have a copy of the "correct" gene, they do not have significant consequences in the bilirubin levels.
With genetic testing (see below) it is possible to determine whether a person has a mutation in the UGT1A1 gene.
A Crigler-Najjar patient (homozygote) has two parents who are unaffected but each parent carries an altered (mutated) copy of the UGT1A1 gene along with a "correct" copy of the gene (heterozygote).
The risk for two heterozygotes (carriers) to have an affected child is 25%, 1 in 4, for each child that they have. In this case the child takes the mutated copy of the gene from each parent. Similarly, there is a 3 in 4 chance (75%) that each child will not be affected by the disease.
Males and females are at equal risk for being affected by Crigler-Najjar syndrome.
Before the use of phototherapy as therapeutic option, Crigler-Najjar syndrome type I was fatal during childhood. Nowadays, patients compliant with this kind of treatment can reach adulthood.
Whether followed by constant medical monitoring Crigler-Najjar patients may successfully give birth to healthy babies.
The risk for a Crigler-Najjar patient (homozygote) having a baby with a unaffected (not carrier) person to have a child affected with the disease is 0%. All children will be carrier (heterozygote) with a copy of the mutated gene and a copy of the correct gene.
As said above, in general population (i.e. in absence of a family history of Crigler-Najjar syndrome) the chance for an unaffected person to have a mutation in the UGT1A1 gene (in other words to be a carrier of the disease) is 1:500.
The risk for a Crigler-Najjar patient (homozygote) having a baby with an unaffected carrier (heterozygote) person to have a child affected with the disease is 50%, for each child they have. There is a remaining 50% chance that the children will be unaffected carriers.
It has been reported that hyperbilirubinemic female Gunn rats (the animal model of Crigler-Najjar syndrome) have reduced fertility (Davis D.R., Yeary R.A. Impaired fertility in the jaundiced female Gunn rat. Lab Anim Sci. 1979;29:739-43). No data are available on fertility of Crigler-Najjar patients.
Here we give links to several clinical reports dealing with patients affected by Crigler-Najjar syndrome during pregnancy.
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Please, remember that these informations are not intended to be a substitute for professional medical advice.
Seek genetic counseling if you are planning a pregnancy and you are affected or have a family history of Crigler-Najjar syndrome.
Molecular diagnosis for Crigler-Najjar syndrome:Genetic testing, including prenatal diagnosis and preimplantation genetic diagnosis , for Crigler-Najjar syndrome type I and type II patients and relatives are possible.
To find laboratories specialized in molecular diagnosis refer to the following websites:
- Orpha.net database
- US National Center for Biotechnology Information
- European Directory of DNA diagnostic Laboratories
- Sir Ganga Ram Hospital, New Delhi, India.
- Clinic for Special Children, Strasburg, PA.
- Mayo Clinic, Rochester, MN.
- Genesis Genetics (preimplatation genetic diagnosis).
- Australian and New Zealand Laboratories.
- Eastern Biotech. Genetic testing in Dubai and Middle East
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