BACKGROUND

Down syndrome or trisomy 21, the most common chromosomal disorder, results from the presence of a third copy of chromosome 21 and manifests as mild to moderate intellectual disability, growth retardation, congenital heart defects, gastrointestinal abnormalities, and characteristic facial features. Several methods have been used to screen for Down syndrome in the prenatal period, such as ultrasound, biomarkers, cell-free DNA testing, and combinations of these tests. A positive result from one or more of these screening tests signals the need for confirmatory karyotyping to clinch the diagnosis. Ultrasound between 11 to 14 weeks of gestation can evaluate nuchal translucency (NT) to screen for Down syndrome. During the second trimester, a triple or quadruple test can also be performed alone or in addition to NT to quantify Down syndrome risk. In limited resource settings however, only the measurement of NT via ultrasound can be performed since biomarker tests are either unavailable or inaccessible. While the diagnostic performance of NT measurement alone has been investigated in several observational studies, there is no consensus on its performance as a sole test to screen for Down syndrome.

To determine the diagnostic performance of NT during prenatal first-trimester ultrasound as a screening test for Down syndrome.

We performed a systematic search on the PubMed, ProQuest, and Cochrane Library databases for recent systematic reviews and meta-analyses that addressed the objective. The existing reviews found were then independently appraised by the two reviewers with the AMSTAR-2 checklist. To update the existing reviews, a systematic search was done in the same databases to identify additional primary diagnostic studies, which were appraised using the QUADAS-2 tool. Random-effects univariate meta-analysis and summary receiving operator curve (HSROC) analysis for the outcomes were performed using Review Manager version 5.4 and R version 4.2.2, respectively. Subgroup analysis was performed by stratifying the baseline risk of mothers for fetal anomaly as low- or high-risk. Highrisk mothers were defined as women with risk factors such as advanced age, positive serum screen, presence of other ultrasound anomalies, and history of previous fetus with anomaly.

We found 22 cohort studies (n=225,846) of women at low-risk for fetal anomaly. The pooled sensitivity was 67.8% (95% CI: 61.4%-73.6%, I2=70.4%) and specificity was 96.3% (95% CI: 95.5%-96.9%, I2=96.7%). For low-risk women, the overall certainty of evidence was low, due to different modes of verification and heterogeneity not completely explained by variability in baseline risk or cut-points. Seven studies (n=9,197) were on high-risk women. The pooled sensitivity was 62.2% (95% CI: 54.1%-69.7%, I2=38.8%) and specificity was 96.5% (95% CI: 93.6%-98.1%, I2=95.5%). For women at high-risk, the evidence was rated as moderate due to differential verification.

Our analysis showed that NT measured through first-trimester ultrasound is specific for Down syndrome but has low sensitivity. Despite this, it is a useful screening test for Down syndrome in low-resource settings where other strategies may not be available or accessible. Furthermore, interpretation of NT results must take into consideration its limited sensitivity as this may lead to missed cases.

BACKGROUND

Down syndrome or trisomy 21, the most common chromosomal disorder, results from the presence of a third copy of chromosome 21 and manifests as mild to moderate intellectual disability, growth retardation, congenital heart defects, gastrointestinal abnormalities, and characteristic facial features. Several methods have been used to screen for Down syndrome in the prenatal period, such as ultrasound, biomarkers, cell-free DNA testing, and combinations of these tests. A positive result from one or more of these screening tests signals the need for confirmatory karyotyping to clinch the diagnosis. Ultrasound between 11 to 14 weeks of gestation can evaluate nuchal translucency (NT) to screen for Down syndrome. During the second trimester, a triple or quadruple test can also be performed alone or in addition to NT to quantify Down syndrome risk. In limited resource settings however, only the measurement of NT via ultrasound can be performed since biomarker tests are either unavailable or inaccessible. While the diagnostic performance of NT measurement alone has been investigated in several observational studies, there is no consensus on its performance as a sole test to screen for Down syndrome.

To determine the diagnostic performance of NT during prenatal first-trimester ultrasound as a screening test for Down syndrome.

We performed a systematic search on the PubMed, ProQuest, and Cochrane Library databases for recent systematic reviews and meta-analyses that addressed the objective. The existing reviews found were then independently appraised by the two reviewers with the AMSTAR-2 checklist. To update the existing reviews, a systematic search was done in the same databases to identify additional primary diagnostic studies, which were appraised using the QUADAS-2 tool. Random-effects univariate meta-analysis and summary receiving operator curve (HSROC) analysis for the outcomes were performed using Review Manager version 5.4 and R version 4.2.2, respectively. Subgroup analysis was performed by stratifying the baseline risk of mothers for fetal anomaly as low- or high-risk. Highrisk mothers were defined as women with risk factors such as advanced age, positive serum screen, presence of other ultrasound anomalies, and history of previous fetus with anomaly.

We found 22 cohort studies (n=225,846) of women at low-risk for fetal anomaly. The pooled sensitivity was 67.8% (95% CI: 61.4%-73.6%, I2=70.4%) and specificity was 96.3% (95% CI: 95.5%-96.9%, I2=96.7%). For low-risk women, the overall certainty of evidence was low, due to different modes of verification and heterogeneity not completely explained by variability in baseline risk or cut-points. Seven studies (n=9,197) were on high-risk women. The pooled sensitivity was 62.2% (95% CI: 54.1%-69.7%, I2=38.8%) and specificity was 96.5% (95% CI: 93.6%-98.1%, I2=95.5%). For women at high-risk, the evidence was rated as moderate due to differential verification.

Our analysis showed that NT measured through first-trimester ultrasound is specific for Down syndrome but has low sensitivity. Despite this, it is a useful screening test for Down syndrome in low-resource settings where other strategies may not be available or accessible. Furthermore, interpretation of NT results must take into consideration its limited sensitivity as this may lead to missed cases.

Humans ; Silver-Russell Syndrome/genetics* ; China ; Consensus

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: To analyze the effect of Y chromosome AZFc microdeletion on pregnancy outcome of intracytoplasmic sperm injection (ICSI). METHODS: From 2016 to 2023, 6 765 cases of oligozoospermia in our hospital were selected as the research objects. The results of Y chromosome microdeletion test were retrospectively analyzed. According to the inclusion exclusion criteria and the principle of propensity distribution 1∶2, 180 patients were included in the study. Sixty patients with Y chromosome AZFc microdeletion and ICSI assisted pregnancy were enrolled into the experimental group. The other 120 patients without Y chromosome microdeletion and ICSI assisted pregnancy were included in the control group. Baseline characteristics, five male sex hormones, laboratory embryo culture and pregnancy outcomes were compared between the two groups. RESULTS: There was no significant difference in male age, female age, infertility years, gravidity and parity between the two groups (P>0.05). There was no significant difference in the five sex hormones of men (P>0.05). Except for transplantable embryos (P<0.05), there was no significant difference in other indicators in the process of embryo culture. There was no difference in pregnancy outcome indicators between the two groups except for the preterm birth rate (P<0.05). CONCLUSION ICSI assisted pregnancy with Y chromosome AZFc microdeletion has no significant effect on pregnancy outcome. And close follow-up of offspring is required.
Humans ; Sperm Injections, Intracytoplasmic ; Pregnancy ; Female ; Chromosomes, Human, Y ; Male ; Chromosome Deletion ; Pregnancy Outcome ; Retrospective Studies ; Sex Chromosome Disorders of Sex Development ; Sex Chromosome Aberrations ; Adult ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Pregnancy Rate

BACKGROUND

Turner syndrome (TS) is the most common sex chromosomal abnormality in females resulting from a missing X chromosomal material. This in turn results in a range of clinical manifestations. This study aimed to provide the data on the cases of TS confirmed via chromosomal analysis in a cytogenetics laboratory in the Philippines as well as the role of genetic counseling.

A review of the karyotyping results of the Cytogenetics Laboratory, Institute of Human Genetics, National Institutes of Health, University of the Philippine Manila from 1991 to 2020.

TS accounted for 2.64% of all the samples received from 1991 to 2020. For 30 years, the most common karyotype in TS was the classical TS or the standard monosomy 45, X noted in 195 patients or 37.69% of all patients diagnosed with TS. Mosaicism with a normal female karyotype was noted in 50 patients (9.62%). For the TS variants, the most common is isochromosome Xq seen in 125 patients (24.04%). This is followed by TS with marker chromosome in 55 patients (10.58%) and ring X chromosome in 23 patients (4.42%). Deletion Xp and deletion Xq were noted in 22 patients (4.23%) and 20 patients (3.85%), respectively.

From this study, it can be noted that chromosomal analysis or standard karyotyping is a vital and useful diagnostic tool in TS. The information obtained from it may be useful in clinical decision-making of families and healthcare providers. Its importance in providing adequate genetic counseling cannot be overemphasized.

Disorders of sex development (DSD) are characterized by atypical development of chromosomal, gonadal, or phenotypic sex. 45X,46XY mosaicism is a type of sex chromosome DSD which presents with a wide heterogeneity of manifestations. We report the case of a 13-year-old phenotypically female who presented with clitoromegaly at puberty. Testosterone level was elevated on serology. Out of the 50 cells examined, 43 cells had Monosomy X while 7 cells had a normal male karyotype. She was managed by a multidisciplinary team. Due to the presence of Y chromosome, the solid nodular structure seen on the right gonad in magnetic resonance imaging and the pain caused by the phallus, Laparoscopic bilateral gonadectomy, salpingectomy and clitoroplasty were done after a shared decision making. Histopathology revealed Gonadoblastoma and Germ cell neoplasia-in-situ of the right gonad justifying timely removal. She was then maintained on estrogen for induction of secondary sexual characteristics.

Turner syndrome and Mayer-Rokitansky-Kuster-Hauser syndrome are the most common causes of primary amenorrhea. However, mullerian agenesis in patients with Turner syndrome is rare, with only 15 reported cases worldwide. Described in this report is an 18-year-old female who presented with primary amenorrhea, absent secondary sexual characteristics, short stature, webbed neck, and shield chest. Work up revealed hypergonadotropic hypogonadism, absence of normal ovaries and uterus, and hypothyroidism. She had a 45,X karyotype and was diagnosed with a very rare case of Turner syndrome with associated Mayer-Rokitansky-Kuster-Hauser syndrome. Early detection of the etiology of amenorrhea is critical for prompt management and initiation of hormonal replacement. She was counseled on the possible systemic problems associated with her condition. The importance of regular follow-up and continuous care were also emphasized. With the coexistence of these two conditions, adoption is the only option for having children in the Philippines, where oocyte donation and uterine transplantation are currently unavailable.
Turner Syndrome ; Mullerian aplasia

Disorders of sexual development (DSD) defined as congenital conditions associated with atypical development of anatomical, gonadal or chromosomal sex, is a rare condition that may present with ambiguous genitalia. Included in the varied classes of DSD is mixed gonadal dysgenesis which is known to be due to mosaicism, a chromosomal aberration. Mosaic individuals may have concerns on growth, hormone balance, gonadal development, sex of rearing and fertility. This case report presents an 18-year old student who presented with primary amenorrhea, delayed secondary sexual characteristics and phenotypic features of Turner syndrome who, on chromosomal analysis revealed 45X0/46XY mosaicism. The patient underwent operative laparoscopy with bilateral gonadectomy on the basis of the increased risk of development of gonadal malignancy in phenotypic females with Y-chromosome material. Histopathological analysis revealed bilateral streak gonads. Hormone replacement therapy was then initiated for the induction of secondary female sex characteristics, as treatment for estrogen deficiency, for the induction of pubertal growth spurt and for optimization of bone mineral accumulation. Management of disorders of sexual development is challenging, thus the need for a multidisciplinary approach involving experts in endocrinology, gynecology, psychology and genetics.
GONADAL DYSGENESIS, MIXED ; MOSAICISM ; TURNER SYNDROME ; CASTRATION