A case of Antley-Bixler syndrome caused by compound heterozygous mutations of the cytochrome P450 oxidoreductase gene.

Antley-Bixler syndrome (ABS) is a skeletal malformation syndrome primarily affecting the skull and limbs. Although causal mutations in the FGFR2 gene have been found in some patients, mutations in the electron donor enzyme P450 oxidoreductase gene (POR) have recently been found to cause ABS in other patients. In addition to skeletal malformations, POR deficiency also causes glucocorticoid deficiency and congenital adrenal hyperplasia with ambiguous genitalia in both sexes. Here, we report on a 7-month-old Korean girl with ABS and ambiguous genitalia who was confirmed by POR gene analysis. Our patient showed typical skeletal findings with brachycephaly, mid-face hypoplasia, and radiohumeral synostosis. She also had partial labial fusion and a single urogenital orifice, as well as increased 17alpha-hydroxyprogesterone levels, suggesting a 21-hydroxylase deficiency. Cortisol and DHEA-sulfate response to rapid adrenocorticotropic hormone (ACTH) stimulation was inadequate. Direct sequencing of the POR gene revealed compound heterozygous mutations (I444fsX449 and R457H). This is the first report of a Korean patient with ABS caused by POR gene mutations.