Antley-Bixler syndrome (ABS) is rare form of craniosynostosis of both autosomal dominant and autosomal recessive inheritance. We are reporting a female term appropriate for gestational age newborn with clinical features of frontal bossing, brachycephaly, proptosis, synostosis of radioulnar joints, hemangioma over nose and philtrum, hydrocephalus suggestive of ABS.
Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland.
* Most steroidogenic enzymes are cytochrome P450s, requiring electron donation from specific proteins (POR or FDXR/FDX), with deficiencies in these proteins linked to various health issues, including the rare CAH caused by POR deficiency.
* Recent research has found mutations in FDXR linked to serious neurological symptoms and adrenal insufficiency, indicating the need for interdisciplinary collaboration among specialists when evaluating these patients.
Cytochrome P450 oxidoreductase deficiency (PORD) is a rare genetic condition causing issues like skeletal deformities, ambiguous genitalia, and menstrual problems due to mutations affecting metabolism and hormone synthesis.
* Advances in molecular biology have improved understanding and diagnosis of PORD, yet challenges remain due to overlapping symptoms with other disorders and lack of treatment guidelines, which can lead to severe complications if mismanaged.
* Timely and accurate diagnosis, possibly through prenatal methods, along with appropriate management, is crucial to improve long-term outcomes and avoid serious health risks like adrenal crises or improper sex assignment.
Objective: To raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD, a rare form of congenital adrenal hyperplasia (CAH), through a case of pregnant woman with virilization symptoms.
Case Description: A 30-year-old Chinese woman was referred to hospital after 7 years of presenting signs of virilization, including voice deepening, acromegaly, hirsutism, clitoromegaly, and acne. These symptoms appeared since her third gestation.
Cytochrome P450 oxidoreductase (POR) is a membrane-bound flavoprotein that helps in transferring electrons from its NADPH domain to all cytochrome P450 (CYP450) enzymes. Mutations in the POR gene could severely affect the metabolism of steroid hormones and the development of skeletal muscles, a condition known as Cytochrome P450 oxidoreductase deficiency (PORD). PORD is associated with clinical presentations of disorders of sex development, Antley and Bixler's syndrome (ABS), as well as an abnormal steroid hormone profile.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:
Recent work has found increasing evidence of mitigated, incompletely penetrant phenotypes in heterozygous carriers of recessive Mendelian disease variants. We leveraged whole-exome imputation within the full UK Biobank cohort (n ∼ 500K) to extend such analyses to 3,475 rare variants curated from ClinVar and OMIM. Testing these variants for association with 58 quantitative traits yielded 102 significant associations involving variants previously implicated in 34 different diseases.
