The disease is inherited as an autosomal recessive trait, meaning that the gene involved is not on one of the sex chromosomes; it also means that in order for a person to have the disorder the genetic change must be present in both copies of the gene, one inherited from the mother and one from the father. In other words, parents of a Crigler-Najjar patient have a copy of the UGT1A1 gene mutated (they are "carriers" of the disease). This do not have a significant effect on the bilirubin levels, since one copy of the gene is functional. In Crigler-Najjar patients both of the copies of the gene are mutated. Two carriers have a 25% chance with each pregnancy of having a child affected by the disorder; a 50% chance of having an unaffected child who is a carrier of the disorder and a 25% chance that the child will not have the disorder and will not be a carrier (see also Crigler-Najjar and pregnancy page).
Several gene alterations have been discovered in Crigler-Najjar syndrome patients, leading to reduced or absent UGT1A1 activity causing hyperbilirubinemia. Full-length cDNA for human UGT1A1 has been cloned and sequenced.
Crigler-Najjar syndrome is very rare, real incidence is unknown (approx. less than 1 case per 1,000,000 births).
