A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita.

Mutations in the gene NR0B1 have been associated with several clinical phenotypes of X-linked adrenal hypoplasia congenita (AHC). The degree and onset of adrenal insufficiency and involvement of hypogonadotropic hypogonadism is variable and may not be concordant with the identified mutation. We review a patient with AHC in which prenatal estriol levels were low, presenting with early-onset mineralocorticoid deficiency in the newborn period followed by glucocorticoid deficiency 2 years later. The reported child is hemizygous for a novel mutation that is deemed de novo in the ligand-binding site of the protein (DAX1) expressed by NR0B1. The identified frameshift mutation results in a T407N/fs protein change. Low prenatal estriol levels may represent a sensitive marker of potentially fatal disorders associated with adrenal insufficiency and should be utilized more frequently. Additionally, accurate reporting of mutations in NR0B1 and the associated phenotype are important to eventually establish a genotype-phenotype correlation that may help anticipate guidance in AHC.