Undetectable maternal serum uE3 and postnatal abnormal sterol and steroid metabolism in Antley–Bixler syndrome

  title={Undetectable maternal serum uE3 and postnatal abnormal sterol and steroid metabolism in Antley–Bixler syndrome},
  author={Deborah Cragun and Sharon K Trumpy and Cedric Shackleton and Richard I Kelley and Nancy D. Leslie and Neil P Mulrooney and Robert J. Hopkin},
  journal={American Journal of Medical Genetics Part A},
Antley–Bixler syndrome (ABS) is a rare condition characterized by radiohumeral synostosis, craniosynostosis, midface hypoplasia, bowing of the femora, multiple joint contractures, and urogenital defects. Several reports have implicated errors of steroid or sterol metabolism in the pathogenesis of ABS. Evidence for this has included association with maternal luteomas, fetal 21‐hydroxylase deficiency, early pregnancy exposure to high‐dose fluconazole, lanosterol 14‐α‐demethylase deficiency, and a… 
Linking Antley–Bixler syndrome and congenital adrenal hyperplasia: A novel case of P450 oxidoreductase deficiency
A new patient with findings of both ABS and CAH is reported that further illustrates how low maternal estriol at prenatal screening can serve as a marker steroid facilitating early diagnosis.
Prenatal diagnosis of P450 oxidoreductase deficiency (ORD): A disorder causing low pregnancy estriol, maternal and fetal virilization, and the Antley–Bixler syndrome phenotype
It is proposed that excessive excretion of epiallopregnanediol together with low estriol may be prenatally diagnostic for OR deficiency (ORD), which is caused by mutations in P450 oxidoreductase (OR), the essential redox partner for CYP17 and CYP21 hydroxylases.
A case of Antley-Bixler syndrome caused by compound heterozygous mutations of the cytochrome P450 oxidoreductase gene
This is the first report of a Korean patient with ABS caused by POR gene mutations, and she showed typical skeletal findings with brachycephaly, mid-face hypoplasia, and radiohumeral synostosis.
Congenital adrenal hyperplasia and P450 oxidoreductase deficiency
P450 oxidoreductase deficiency (ORD) has a complex phenotype including two unique features not observed in any other CAH variant, skeletal malformations and severe genital ambiguity in both sexes, with a specific focus on ORD.
Cytochrome P450 Oxidoreductase Deficiency with Antley-Bixler Syndrome: Steroidogenic Capacities
Hormonal responses to actual physical stress were as follows: Vigorous crying during blood sampling rarely affected the serum cortisol level, and intravenous hydrocortisone administration even at a dose of 6 mg/kg, which is lower than that recommended for congenital adrenal hyperplasia in Japan, proved to be excessive.
Prenatal Diagnosis of Congenital Adrenal Hyperplasia Caused by P450 Oxidoreductase Deficiency
Prenatal diagnosis in PORD is readily established via urinary steroid metabolite analysis of maternal urine, and visible malformations at prenatal ultrasound predict a severe malformation phenotype.
P450 oxidoreductase deficiency and Antley–Bixler syndrome
  • W. Arlt
  • Biology, Medicine
    Reviews in Endocrine and Metabolic Disorders
  • 2007
Evidence is provided for a differential interaction of specific POR mutations with different electron-accepting P450 enzymes and this may provide the key for further understanding of the complex pathogenesis of this complex disease.
Cytochrome P450 Oxidoreductase Deficiency in Three Patients Initially Regarded as Having 21-Hydroxylase Deficiency and/or Aromatase Deficiency: Diagnostic Value of Urine Steroid Hormone Analysis
Clinical features in PORD can be similar to those in 21-OHD or aromatase deficiency, and that comprehensive assessment of the pregnant course, physical examination, and adrenal and gonadal function studies is essential for the precise diagnosis of PORD.
Sonographic Diagnosis of Antley-Bixler PORD-Type Syndrome
A case of PORD with the ABS phenotype diagnosed by sonography in utero at an early gestation (13–16 weeks), which included mutations in the POR gene is presented.
Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency: implication for the backdoor pathway to dihydrotestosterone.
The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrostersone excretions in the same period, suggests the presence of the backdoor pathway in PORD.


Features of Antley-Bixler syndrome in an infant born to a mother with pregnancy luteoma
A newborn girl with manifestations of the Antley-Bixler syndrome showed severe virilization probably caused by the association of a mild 21-hydroxylase deficiency and maternal hyperandrogenism due to a pregnancy luteoma.
Prenatal detection of X‐linked ichthyosis by maternal serum screening for down syndrome
From dermatological diagnosis, prenatal uE3 levels, and pedigree analysis, it is concluded that at least 5 in approximately 7500 male births in the study population are affected by steroid sulphatase deficiency, which is the biochemical defect in X‐linked ichthyosis.
Dehydro‐oestriol and dehydropregnanetriol are candidate analytes for prenatal diagnosis of Smith‐Lemli‐Opitz syndrome
It is proposed that the measurement of DHE3 and DHPT in maternal urine and serum may allow non‐invasive antenatal diagnosis of SLOS.
Antley-Bixler syndrome in sisters: a term newborn and a prenatally diagnosed fetus.
The Antley-Bixler syndrome is a recognizable malformation syndrome with a probable autosomal recessive mode of inheritance, which can be diagnosed in the fetus by midtrimester ultrasound examination.
Prenatal diagnosis of the RSH/Smith-Lemli-Opitz syndrome.
It is concluded that accurate prenatal diagnosis of RSH/ SLOS is possible by sterol analysis of AF and, most likely, CV specimens as well and that MSuE3 levels in combination with sonography may provide useful diagnostic and prognostic information in the absence of a family history of R SH/SLOS.
Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?
Findings suggest that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, and allow a hypothesis to be formulated under which it may explain all the differing and seemingly contradictory circumstances in which the Antleys Bixler phenotype has been recognised.
Gas chromatographic steroid analysis for diagnosis of placental sulfatase deficiency: a study of nine patients.
The excretion of 11 urinary steroid sulfates was compared in 9 pregnancies with placental sulfatase deficiency (PSD) proven by in vitro incubation experiments, 1 pregnancy associated with fetal
Differential diagnosis and management of very low second trimester maternal serum unconjugated estriol levels, with special emphasis on the diagnosis of X-linked ichthyosis.
The differential diagnosis of very low and undetectable levels of unconjugated estriol in maternal serum is discussed, with special emphasis on the prenatal diagnosis of X-linked ichthyosis.