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Medical Archives (Sarajevo, Bosnia and... 2023Aplasia cutis congenita is a heterogeneous disorders group with a rare reported incident of 0.5 to 1 in 10,000 births. ACC can be associated with physical defects or...
BACKGROUND
Aplasia cutis congenita is a heterogeneous disorders group with a rare reported incident of 0.5 to 1 in 10,000 births. ACC can be associated with physical defects or syndrome that may help in diagnosis, prognosis and further evaluation of the patient. Trisomy 13 is one of the most common fetal life limiting diagnosis which is associated with ACC of membranous type scalp.
OBJECTIVE
In this article, we report cases of aplasia cutis congenita of the scalp with dura and bone defect and exposed sagittal sinus in newborn diagnosed to have trisomy 13. It emphasizes the importance of ACC associated syndrome which is having high mortality prior to surgical intervention.
CASE PRESENTATION
The patient was born at 35 weeks of gestation. Her physical examination revealed a newborn girl with dysmorphic facial features including widely separated eyes, downward slanting of the palpebral fissure, microphthalmia, retrognathia, and low seat ears. She had area of loss of scalp skin and skull bone with seen brain tissue and sagittal sinus were exposed that was measure 6 by 5 cm in size. Additionally, she had a clenched fist and overlapping fingers and rocker bottom feet. Laboratory investigations include basic labs and the TORCH screen was negative. On the 9th day of life, a chromosomal analysis showed a female karyotype with three copies of chromosome number 13 in all 20 metaphase cells counts.
CONCLUSION
The patient was managed conservatively. However, a multidisciplinary team agreed on do not resuscitate with no further surgical intervention as survival rate of trisomy 13 is poor.
Topics: Humans; Infant, Newborn; Female; Scalp; Trisomy 13 Syndrome; Ectodermal Dysplasia; Skull; Brain
PubMed: 37876568
DOI: 10.5455/medarh.2023.77.319-322 -
Prenatal Diagnosis Nov 2023To assess whether the fetal fraction (FF) has an impact on the screen-positive rate (SPR) in cell-free DNA (cfDNA) screening for trisomy 21.
OBJECTIVE
To assess whether the fetal fraction (FF) has an impact on the screen-positive rate (SPR) in cell-free DNA (cfDNA) screening for trisomy 21.
METHODS
Retrospective analysis based on samples analyzed using the Harmony Prenatal Test (Roche Inc). Due to the size of the data set, we focused on the SPR, which was stratified according to the maternal age, weight, gestational age, and FF distribution.
RESULTS
The study cohort consisted of 364,881 patients, including 2614 with a high-risk-result. Median maternal and gestational ages were 34.6 years and 12.4 weeks. FF was dependent on maternal age, weight, and gestational age. SPR was 0.72% and it was independent of maternal weight but was dependent on maternal age. There was a positive but weak association between the FF and the SPR until the FF reached 20.0% (OR p = 1.021, p < 0.001, Nagelkerkes r2 = 0.001). This group included 357,800 pregnancies or 98.1% of the study population. In the group of pregnancies with a FF > 20%, the association was stronger (OR 1.099, p < 0.001, Nagelkerkes r2 = 0.042).
CONCLUSION
The SPR in cfDNA screening for trisomy 21 was relatively constant up to a FF of about 20%.
Topics: Pregnancy; Female; Humans; Down Syndrome; Trisomy; Retrospective Studies; Cell-Free Nucleic Acids; Prenatal Diagnosis; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 37789581
DOI: 10.1002/pd.6448 -
Molecular Diagnosis & Therapy Nov 2023We aimed to evaluate the clinical performance of expanded noninvasive prenatal testing (NIPT-Plus) for the detection of aneuploidies and microdeletion/microduplication...
OBJECTIVE
We aimed to evaluate the clinical performance of expanded noninvasive prenatal testing (NIPT-Plus) for the detection of aneuploidies and microdeletion/microduplication syndromes.
METHODS
A total of 7177 pregnant women were enrolled in the study from June 2020 to March 2022 at Xijing Hospital, China. Cases with NIPT-Plus-positive results were further confirmed by chromosomal karyotyping and a chromosomal microarray analysis.
RESULTS
A total of 112 positive cases (1.56%) were identified by NIPT-Plus, including 60 chromosome aneuploidies and 52 microdeletion/microduplication syndromes. Ninety-five cases were validated by amniocentesis, and 57 were confirmed with true-positive results, comprising 18 trisomy 21, 4 trisomy 18, 1 trisomy 13, 17 sex chromosome aneuploidies, 1 other aneuploidy, and 16 microdeletion/microduplication syndromes. The positive predictive value of total chromosomal abnormalities was 60% (57/95). For trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, other aneuploidies and microdeletion/microduplication syndromes, the sensitivity was all 100%, the specificity was 100, 99.986, 100, 99.888, 99.958, and 99.636%, and the positive predictive value was 100, 80, 100, 68, 25, and 38.10%, respectively. For all clinical characteristics, the abnormal maternal serum screening group was found to have the highest prevalence of chromosomal abnormalities (1.54%), and the ultrasound abnormality group presented the highest positive predictive value (73.33%).
CONCLUSIONS
NIPT-Plus has great potential for the detection of aneuploidies and microdeletion/microduplication syndromes owing to its high sensitivity, safety, and specificity, which greatly reduces unnecessary invasive procedures and the risk of miscarriage and allows informed maternal choice.
Topics: Female; Pregnancy; Humans; Down Syndrome; Noninvasive Prenatal Testing; Trisomy 18 Syndrome; Prenatal Diagnosis; Trisomy 13 Syndrome; Aneuploidy; Chromosome Aberrations
PubMed: 37689607
DOI: 10.1007/s40291-023-00674-x -
American Journal of Medical Genetics.... Nov 2023In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary...
In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary pediatric center. We compared survival and survival to discharge rates between patients who underwent tracheostomies during their NICU stays (T group, n = 8) and those who did not (non-T group, n = 11). A total of 19 patients enrolled. Median survival in all patients was 673 (266-1535) days. Significant differences in the 1-, 2-, and 3-year survival rates were found between the T and the non-T groups (100% vs. 46%, p = 0.018; 88% vs. 18%, p = 0.006; 63% vs. 9%, p = 0.041, respectively). The survival to discharge rate was higher in the T versus non-T group (75% vs. 45%, p = 0.352). This study highlights a significantly higher long-term survival of patients with trisomy 13 syndrome who underwent tracheostomies during their NICU stays.
PubMed: 37658587
DOI: 10.1002/ajmg.a.63393 -
Chromosome Research : An International... Aug 2023Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans... (Review)
Review
Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans include trisomies of chromosomes 21, 18, or 13, which cause Down, Edwards, or Patau syndromes, respectively. While individuals with trisomy 18 or 13 die soon after birth, people with Down syndrome live to adulthood but have intellectual disabilities and are prone to multiple diseases. At the cellular level, mistakes in the segregation of a single chromosome leading to a cell losing a chromosome are lethal. In contrast, the cell that gains a chromosome can survive. Several studies support the hypothesis that gaining an extra copy of a chromosome causes gene-specific phenotypes and phenotypes independent of the identity of the genes encoded within that chromosome. The latter, referred to as aneuploidy-associated phenotypes, are the focus of this review. Among the conserved aneuploidy-associated phenotypes observed in yeast and human cells are lower viability, increased gene expression, increased protein synthesis and turnover, abnormal nuclear morphology, and altered metabolism. Notably, abnormal nuclear morphology of aneuploid cells is associated with increased metabolic demand for de novo synthesis of sphingolipids. These findings reveal important insights into the possible pathological role of aneuploidy in Down syndrome. Despite the adverse effects on cell physiology, aneuploidy is a hallmark of cancer cells. Understanding how aneuploidy affects cell physiology can reveal insights into the selective pressure that aneuploid cancer cells must overcome to support unlimited proliferation.
Topics: Humans; Down Syndrome; Sex Chromosomes; Aneuploidy; Trisomy; Chromosome Segregation
PubMed: 37620607
DOI: 10.1007/s10577-023-09732-w -
American Journal of Perinatology May 2024Trisomy 13 (T13) and 18 (T18) are aneuploidies associated with multiple structural congenital anomalies and high rates of fetal demise and neonatal mortality....
OBJECTIVE
Trisomy 13 (T13) and 18 (T18) are aneuploidies associated with multiple structural congenital anomalies and high rates of fetal demise and neonatal mortality. Historically, patients with either one of these diagnoses have been treated similarly with exclusive comfort care rather than invasive interventions or intensive care, despite a wide phenotypic variation and substantial variations in survival length. However, surgical interventions have been on the rise in this population in recent years without clearly elucidated selection criterion. Our objective was to create a standardized approach to counseling expectant persons and parents of newborns with T13/T18 in order to provide collaborative and consistent counseling and thoughtful approach to interventions such as surgery.
STUDY DESIGN
This article describes our process and presents our resulting clinical care guideline.
RESULTS
We formed a multi- and interdisciplinary committee. We used published literature when available and otherwise expert opinion to develop an approach to care featuring individualized assessment of the patient to estimate qualitative mortality risk and potential to benefit from intensive care and/or surgeries centered within an ethical framework.
CONCLUSION
Through multidisciplinary collaboration, we successfully created a patient-centered approach for counseling families facing a diagnosis of T13/T18. Other institutions may use our approach as a model for developing their own standardized approach.
KEY POINTS
· Trisomy 13 and trisomy 18 are associated with high but variable morbidity and mortality.. · Research on which patients are most likely to benefit from surgery is lacking.. · We present our institution's framework to counsel families with fetal/neonatal T13/T18..
Topics: Humans; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Chromosomes, Human, Pair 18; Trisomy; Infant, Newborn; Female; Parents; Chromosomes, Human, Pair 13; Chromosome Disorders; Pregnancy; Counseling; Genetic Counseling
PubMed: 37619598
DOI: 10.1055/s-0043-1772748 -
Diagnostics (Basel, Switzerland) Aug 2023Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward... (Review)
Review
Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward Syndrome (T18), and Down syndrome (T21). It comprises a simple technique involving the analysis of cell-free foetal DNA (cffDNA) obtained through maternal serum, using advances in next-generation sequencing. NIPT has shown promise as a simple and low-risk screening test, leading various governments and private organizations worldwide to dedicate significant resources towards its integration into national healthcare initiatives as well as the formation of consortia and research studies aimed at standardizing its implementation. This article aims to review the reliability of NIPT while discussing the current challenges prevalent among different communities worldwide.
PubMed: 37568933
DOI: 10.3390/diagnostics13152570 -
Current Opinion in Pediatrics Oct 2023To review the incidence of congenital heart disease in the trisomies, highlight the history of cardiac surgery in trisomy 21 comparing it to the increase in cardiac... (Review)
Review
PURPOSE OF REVIEW
To review the incidence of congenital heart disease in the trisomies, highlight the history of cardiac surgery in trisomy 21 comparing it to the increase in cardiac surgery in trisomies 13 and 18, discuss ethical issues specific to trisomies 13 and 18, and suggest a pathway of shared decision-making in the management of congenital heart disease in trisomy 13 and 18, specifically congenital heart surgery.
RECENT FINDINGS
Congenital heart disease is prevalent in the trisomies and the management of these defects, especially surgical intervention, has changed. In the late 20th century, survival after cardiac surgery in trisomy 21 vastly improved, significantly decreasing morbidity and mortality secondary to pulmonary hypertension. Similarly, procedures and surgeries have been performed with increasing frequency in trisomy 13 and 18 patients and concomitantly, survival in this patient population is increasing. Yet across the United States, the willingness to perform cardiac surgery in trisomy 13 and 18 is variable, and there is ethical controversy about the correct action to take. To address this concern, a shared decision-making approach with an informed parent(s) is advised.
SUMMARY
As the care and management of congenital heart disease changed in trisomy 21, so too it has with trisomy 13 and 18. Physicians and parents should develop goal-directed treatment plans balancing the risk versus benefit and consider cardiac surgical repair if feasible and beneficial.
Topics: Humans; United States; Trisomy 13 Syndrome; Trisomy; Down Syndrome; Heart Defects, Congenital; Cardiac Surgical Procedures; Trisomy 18 Syndrome
PubMed: 37551160
DOI: 10.1097/MOP.0000000000001278 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Aug 2023To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal...
OBJECTIVE
To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women.
METHODS
A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes.
RESULTS
Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found.
CONCLUSION
NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.
Topics: Child; Female; Pregnancy; Humans; Retrospective Studies; Cell-Free Nucleic Acids; Chromosome Disorders; Prenatal Diagnosis; Down Syndrome; Sex Chromosome Aberrations; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Aneuploidy; DNA; Trisomy
PubMed: 37532491
DOI: 10.3760/cma.j.cn511374-20220815-00545 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Aug 2023To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT).
OBJECTIVE
To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT).
METHODS
The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor.
RESULTS
The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples.
CONCLUSION
NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.
Topics: Humans; Female; Pregnancy; Trisomy 13 Syndrome; DNA Copy Number Variations; Placenta; Chromosomes, Human, Pair 1; In Situ Hybridization, Fluorescence; Prenatal Diagnosis; Fetus; Amniotic Fluid; Chromosome Aberrations; Trisomy
PubMed: 37532489
DOI: 10.3760/cma.j.cn511374-20220818-00560