Abstract
BackgroundAntley-Bixler syndrome (ABS) caused by P450 oxidoreductase deficiency (PORD) is a congenital adrenal hyperplasia with skeletal malformations and disordered sex development in both sexes. There have been no reports of ABS caused by PORD in Chinese children.MethodsWe described the clinical and genetic characteristics of eight Chinese children with ABS caused by PORD and compared them with those of subjects in previous studies.ResultsEight patients, aged 6 months–17.8 years, showed strikingly similar craniofacial malformations. We first described four unreported features: lower eyelid fat pads (4/8), prominent lower eyelid-zygoma transverse line (4/8), underdeveloped or absent antihelix (5/8) and single earlobe crease (5/8). Five 46, XY patients presented various degrees of undervirilization, while three 46, XX cases showed masculinization. Basal endocrine measurements revealed the following consistent results: normal cortisol; elevated adrenocorticotropic hormone, progesterone, pregnenolone, 17-hydroxypropgesterone, and corticosterone; and decreased or normal testosterone/oestradiol. We identified three previously reported variants and four novel variants (c.51719_51710delGGCCCCTGTGinsC, p.D210G, p.Y248X and p.R554X) of POR. The most prevalent variant was p.R457H (8/16). The hydrocortisone dosages of patients differed because of variable degrees of adrenal insufficiency.ConclusionsWe described novel phenotypes and genotypes of ABS caused by PORD. The variant p.R457H was the most prevalent in this cohort. All subjects had combined characteristics of 17-hydroxylase and 21-hydroxylase deficiency. Steroid replacement therapy for patients with PORD requires individually tailored dosing.
Highlights
Antley-Bixler syndrome (ABS) caused by P450 oxidoreductase deficiency (PORD) is a congenital adrenal hyperplasia with skeletal malformations and disordered sex development in both sexes
In 2004, Fluck et al [3] found that the electron donor enzyme P450 oxidoreductase (POR) gene mutated into another pathogenic gene of ABS combined with urogenital defects
Case report Patient 1 A child with a 46, XX karyotype was diagnosed with ABS caused by PORD in our centre at the age of 4.2 years
Summary
Antley-Bixler syndrome (ABS) caused by P450 oxidoreductase deficiency (PORD) is a congenital adrenal hyperplasia with skeletal malformations and disordered sex development in both sexes. There have been no reports of ABS caused by PORD in Chinese children. Antley-Bixler syndrome (ABS) is a rare congenital malformation syndrome associated with midface hypoplasia, bilateral radiohumeral synostosis, multiple joint contractures, femoral bowing, long bone fractures and, occasionally, urogenital or cardiac defects [1]. ABS was first reported in 1975 [2] and was initially thought to be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. In 2004, Fluck et al [3] found that the electron donor enzyme P450 oxidoreductase (POR) gene mutated into another pathogenic gene of ABS combined with urogenital defects. POR provides electrons to major drug-metabolizing cytochrome P450 (CYP) enzymes, among which five CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) are responsible for the metabolism of more than 80% of all drugs [6]
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