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2018-03-24

Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia: Experience from a tertiary care centre in India.

Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia: Experience from a tertiary care centre in India.

Indian J Med Res. 2017 Feb;145(2):194-202

Authors: Dubey S, Tardy V, Chowdhury MR, Gupta N, Jain V, Deka D, Sharma P, Morel Y, Kabra M

Abstract

BACKGROUND & OBJECTIVES: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with a wide range of clinical manifestations. The disease is attributed to mutations in CYP21A2 gene encoding 21-hydroxylase enzyme. In view of severe phenotype in salt-losing cases, issues related to genital ambiguity in girls and precocity in boys, most families opt for prenatal testing and termination of affected foetus. CAH can be diagnosed in utero through direct molecular analysis of CYP21A2 gene, using DNA extracted from foetal tissues or cells obtained from chorionic villus sampling or amniocentesis. The objective of this study was to evaluate the feasibility and accuracy of prenatal diagnosis (PND) using sequencing and multiplex ligation probe amplification (MLPA) methods in families at risk for CAH.

METHODS: Fifteen pregnant women at risk of having an affected offspring with CAH were included in this study. Ten families had previous affected children with salt-wasting/simple virilising form of CAH and five families did not have live children but had a high index of suspicion for CAH in previous children based on history or records. Mutation analysis was carried out by Sanger sequencing and MLPA method.

RESULTS: Seven different mutations were identified in 15 families. Deletions and I2g mutation were the most common. Of the 15 foetuses analyzed, nine were unaffected while six were affected. Unaffected foetuses were delivered, they were clinically normal and their genotype was found to be concordant to the prenatal report. All except two families reported in the second trimester. None of the couples opted for prenatal treatment.

INTERPRETATION & CONCLUSIONS: Our preliminary findings show that PND by direct mutation analysis along with MLPA is a feasible strategy that can be offered to families at risk.

2018-02-09

Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism.

Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism.

Arch Argent Pediatr. 2016 Oct 01;114(5):e362-5

Authors: Serapinas D, Bartkeviciene D, Valantinaviciene E, Machtejeviene E

Abstract

The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) offers pregnant women a more accurate method than traditional serum screening methods for detecting fetal aneuploidies. Clinical trials have demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However NIPT approaches that take advantage of single-nucelotide polymorphism (SNP) information potentially allow the identification of triploidy, chromosomal microdeletion syndromes and other unusual genetic variants. To highlight this approach of NIPT we present a rare case of confined placental X chromosome monosomy mosaicism that was prenatally suspected with a single-nucleotide polymorphism-based noninvasive prenatal test. The results of invasive tests (amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46, XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX), confirming that mosaicism was limited to the placenta. These results highlight the need of patient's informed consent and thorough pretest and postest counseling to ensure that they understand the limitations and advantages of the tests and the implications of the resultss.

Turner Syndrome: Diagnostic and Management Considerations for Perinatal Clinicians.

Turner Syndrome: Diagnostic and Management Considerations for Perinatal Clinicians.

Clin Perinatol. 2018 Mar;45(1):119-128

Authors: Redel JM, Backeljauw PF

Abstract

The perinatal clinician needs to understand certain essential concepts when encountering an infant with a suspected or confirmed diagnosis of Turner syndrome. This article describes the key clinical features that should prompt testing, the appropriate diagnostic workup, the necessary screening required after diagnosis, and how to best approach family counseling.

2017-11-11

Mismatch between fetal sexing and birth phenotype: a case of complete androgen insensitivity syndrome.

Mismatch between fetal sexing and birth phenotype: a case of complete androgen insensitivity syndrome.

Endocr J. 2017 Nov 09;:

Authors: Yoshii K, Naiki Y, Terada Y, Fukami M, Horikawa R

Abstract

With advancing maternal age, the number of prenatal genetic tests is increasing in many countries. Prenatal genetic tests, such as amniocentesis, chorionic villus sampling and non-invasive prenatal testing, can disclose fetal chromosomal sex, although these tests were originally designed to prenatally diagnose chromosomal aneuploidies, such as trisomy 21, 18 and 13. Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder caused by an androgen receptor dysfunction leading to hormone resistance. The affected individuals are genetic males as shown by 46,XY but present complete female external genitalia and normal breast development at puberty albeit without menstruation. CAIS is commonly diagnosed in adolescence based on primary amenorrhea or in childhood based on inguinal hernia or testis-like masses in the inguinal region. In the present report, we describe a baby in whom CAIS was diagnosed immediately after birth based on a mismatch between the fetal karyotype detected by amniocentesis and the external genitalia phenotype at birth. We speculate that the increase in the number of prenatal genetic tests is contributing to the early detection of 46,XY disorders of sex development, especially those previously called complete sex reversal, which is supposedly diagnosed during childhood or adolescence. Hence, it is necessary to understand the disease-specific hormone profile at each developmental stage for accurate diagnosis.

2013-10-13

Counseling parents before prenatal diagnosis: Do we need to say more about the sex chromosome aneuploidies?

Am J Med Genet A. 2013 Sep 24. doi: 10.1002/ajmg.a.36226. [Epub ahead of print]

Counseling parents before prenatal diagnosis: Do we need to say more about the sex chromosome aneuploidies?

Lalatta F, Tint GS.


Source

Clinical Genetics Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy.


Abstract


Sex chromosome trisomies (SCT), an extra X chromosome in females (triple X, XXX), males with an extra X chromosome (Klinefelter syndrome, XXY) or an extra Y chromosome (XYY) occur because of errors during meiosis and are relatively frequent in humans. Their identification has never been the goal of prenatal diagnosis (PD) but they almost never escape detection by any of the methods commonly in use. Despite recommendations and guide-lines which emphasize the importance of structured counseling before and after PD, most women remain unaware that testing for serious genetic abnormalities is more likely to uncover these trisomies. With the increasing use of PD more and more prospective parents receive a diagnosis of sex chromosome trisomies and are faced with the dilemma of whether to terminate the pregnancy or to carry it to term. Despite the dramatic and emotionally devastating consequences of having to make such a decision, they have little opportunity to consider in advance the possible outcomes of such a pregnancy and, rather than relying on their own feelings and judgements, are forced to depend on the advice of counseling professionals who may or may not themselves be fully aware of what having an extra sex chromosome can mean to the development of a child. We address here the principles of reproductive autonomy together with an analysis of the major issues that ought to be discussed with the parents before a PD is carried out in order to minimize detrimental effects caused by this unexpected finding. © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.