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Frontiers in Medicine 2024The objective of this study was to investigate the attitudes of healthcare professionals (HPs) working in the prenatal setting toward uncertain results (UR) from...
OBJECTIVE
The objective of this study was to investigate the attitudes of healthcare professionals (HPs) working in the prenatal setting toward uncertain results (UR) from prenatal exome sequencing (pES) in China.
METHODS
We conducted a national survey among HPs working in the prenatal setting. UR in our study include variants of uncertain significance (VUS), variants with variable penetrance/expressivity (VVPE), and secondary findings unrelated to the indication for testing (SFs). A total of 285 questionnaires that met the inclusion criteria were collected. Data were analyzed using IBM SPSS Statistics 26.
RESULTS
When performing the pre-test counseling, only 7.4% of HPs mentioned the possibility of VUS, 6.3% discussed the possibility of VVPE, and 7.4% introduced the SFs with parents with the option to not report these variants. In post-test counseling, 73.0-82.8% HPs discussed with the parents but did not make any recommendations for managing the pregnancy after reporting UR (73.0% for VUS, 82.8% for VVPE, 74.7% for SFs, respectively).
CONCLUSION
Most parents did not have the option of opting out of reporting UR from pES in pre-test counseling. UR did not influence the pregnancy recommendation made by most HPs. Establishing national guidelines for reporting UR from pES and developing strategies to improve counseling skills may help HPs manage UR.
PubMed: 38813373
DOI: 10.3389/fmed.2024.1335649 -
SAGE Open Medical Case Reports 2024Prune belly syndrome is a rare disorder that occurs mainly in men. It is characterized by the triad of deficient abdominal wall muscles, the dilated urinary collecting...
Prune belly syndrome is a rare disorder that occurs mainly in men. It is characterized by the triad of deficient abdominal wall muscles, the dilated urinary collecting system, bilateral cryptorchidism, and infertility. It mainly affects the genitourinary system, which involves the prognosis. We present the case of a preterm neonate male whose diagnosis of a prune belly was suspected in antenatal ultrasound. He had a urinary tract abnormality starting at 22 weeks of gestation. At birth, a clinical examination revealed a distended abdomen within a wrinkled and flaccid abdominal wall, a macropenis, and bilateral cryptorchidism. A urinary tract ultrasound revealed a right pyelocaliciel dilatation and a right megaureter with a megacystis. The neonate ultimately died due to severe renal failures. Prune Belly syndrome is a complex disease with a high mortality rate. Early antenatal ultrasound may ameliorate the prognosis.
PubMed: 38812837
DOI: 10.1177/2050313X241258850 -
Frontiers in Endocrinology 2024Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by... (Review)
Review
Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by exposure to exogenous androgens. The most common cause of 46,XX disorders/differences in sex development (DSD) is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, comprising >90% of 46,XX DSD cases. Deficiencies of 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, and P450-oxidoreductase (POR) are rare types of CAH, resulting in 46,XX DSD. In all CAH forms, patients have normal ovarian development. The molecular genetic causes of 46,XX DSD, besides CAH, are uncommon. These etiologies include primary glucocorticoid resistance (PGCR) and aromatase deficiency with normal ovarian development. Additionally, 46,XX gonads can differentiate into testes, causing 46,XX testicular (T) DSD or a coexistence of ovarian and testicular tissue, defined as 46,XX ovotesticular (OT)-DSD. PGCR is caused by inactivating variants in , resulting in glucocorticoid insensitivity and the signs of mineralocorticoid and androgen excess. Pathogenic variants in the gene lead to aromatase deficiency, causing androgen excess. Many genes are involved in the mechanisms of gonadal development, and genes associated with 46,XX T/OT-DSD include translocations of the ; copy number variants in , , , , , and , and sequence variants in , , , , , , and . Progress in cytogenetic and molecular genetic techniques has significantly improved our understanding of the etiology of non-CAH 46,XX DSD. Nonetheless, uncertainties about gonadal function and gender outcomes may make the management of these conditions challenging. This review explores the intricate landscape of diagnosing and managing these conditions, shedding light on the unique aspects that distinguish them from other types of DSD.
Topics: Humans; Adrenal Hyperplasia, Congenital; 46, XX Disorders of Sex Development; Female; Male; Disorders of Sex Development
PubMed: 38812815
DOI: 10.3389/fendo.2024.1354759 -
Radiology Case Reports Aug 2024Double aortic arch (DAA) is a rare congenital abnormality characterized by a vascular ring that often requires surgical intervention due to respiratory complications....
Double aortic arch (DAA) is a rare congenital abnormality characterized by a vascular ring that often requires surgical intervention due to respiratory complications. The DAA and right aortic arch with mirror-image branches (RAA-MB) represent abnormalities in development of the aortic arch. However, prognosis differs significantly, as the DAA forms vascular rings, whereas the RAA-MB typically does not. Distinguishing between the conditions becomes particularly challenging in cases of DAA with closure of the posterior portion of the left aortic arch (LAA) because the postnatal manifestations closely resemble those of RAA-MB. Herein, we present a case of DAA in which longitudinal observation of the LAA and RAA diameters during pregnancy aimed in predicting postnatal closure of the LAA. A 37-year-old female with suspected DAA was referred to our hospital at 26 weeks of gestation. Initial measurements revealed comparable diameters for the LAA and RAA; however, the LAA diameter decreased to approximately half that of the RAA by term owing to growth restrictions. Postnatal contrast computed tomography confirmed the closure of the posterior portion of the LAA and RAA with Kommerell diverticulum. Our findings suggest that careful monitoring of DAA throughout fetal development, especially during the third trimester, may aid in predicting atretic changes in the nondominant arch after birth, allowing an easy distinction between the DAA and RAA-MB after birth.
PubMed: 38812596
DOI: 10.1016/j.radcr.2024.04.060 -
The Journal of Maternal-fetal &... Dec 2024Deep vein thrombosis (DVT) is a common complication in obstetrics that needs early interaction. The study examined the expression change and clinical value of long...
OBJECTIVE
Deep vein thrombosis (DVT) is a common complication in obstetrics that needs early interaction. The study examined the expression change and clinical value of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in DVT early diagnosis.
METHODS
One hundred patients with DVT after delivery and 100 healthy parturients without DVT were enrolled. Serum samples were collected one day before delivery and received qRT-PCR for mRNA detection. Prenatal coagulation markers including prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen (FIB) and thrombin time (TT), D-dimer (D-D), thrombomodulin (TM), and peroxidase anti-peroxidase soluble complex (PAP) were tested. The receiver operating characteristic (ROC) curve was drawn for the diagnostic value assessment.
RESULTS
LncRNA CRNDE levels increased remarkably in the serum of DVT patients compared with the healthy controls, which were negatively correlated with serum concentration of PT, APTT, and TT while positively correlated with FIB, D-D, TM, and PAP. Serum CRNDE (HR = 5.973, 95% CI = 2.990-11.933, < .001) was independently related to the occurrence of DVT after delivery. Then, ROC curve using serum CRNDE showed a good diagnostic value for DVT with the AUC of 0.899. ROC curve of ultrasonography combined with CRNDE produced an AUC of 0.968, and both sensitivity and specificity were enhanced compared to a single indicator.
CONCLUSIONS
The increase of CRNDE level was an independent risk factor for postpartum DVT. Prenatal ultrasonography combined with CRNDE can improve the predictive efficacy for DVT.
Topics: Humans; Female; RNA, Long Noncoding; Pregnancy; Adult; Venous Thrombosis; Case-Control Studies; Ultrasonography, Prenatal; Predictive Value of Tests; Postpartum Period; Lower Extremity; Biomarkers; ROC Curve
PubMed: 38812363
DOI: 10.1080/14767058.2024.2352089 -
Frontiers in Pediatrics 2024Familial hemophagocytic lymphohistiocytosis (FHLH) is an inherited life-threatening disease. Five types are identified, with the addition of congenital immunodeficiency...
BACKGROUND
Familial hemophagocytic lymphohistiocytosis (FHLH) is an inherited life-threatening disease. Five types are identified, with the addition of congenital immunodeficiency syndromes in which HLH is a typical manifestation. The literature on this disease is very scarce in the Middle East, with only a few scattered reports.
METHODS
We report detailed demographic, clinical, and genomic data from 28 patients diagnosed with primary and familial HLH over the last decade in Qatar. An evaluation was performed of allele frequencies of deleterious variants from 12 primary and familial HLH causative genes on the Qatar Genome Programme (QGP) cohort of 14,669 Qatari individuals.
RESULTS
The genetic diagnosis was obtained in 15 patients, and four novel mutations in (), , , and genes were found. We identified 22,945 low/high/moderate/modifier impact variants significantly enriched in the QGP in those 12 genes. The variants rs1271079313 in and rs753966933 in found in our patient cohort were significantly more prevalent in the QGP compared to the Genome Aggregation Database (gnomAD) database, with a high carrier frequency in the Qatari population.
CONCLUSIONS
We established the first primary and familial HLH Registry in the Gulf Region and identified novel possibly pathogenic variants present at higher frequency in the Qatari population, which could be used for screening purposes. Raising awareness about primary and familial HLH and implementing screening activities in the Qatari highly inbred population could stem into more comprehensive premarital and prenatal evaluations and faster diagnosis.
PubMed: 38808104
DOI: 10.3389/fped.2024.1326489 -
Frontiers in Neuroscience 2024Fetal alcohol spectrum disorders include a variety of physical and neurocognitive disorders caused by prenatal alcohol exposure. Although their overall prevalence is...
INTRODUCTION
Fetal alcohol spectrum disorders include a variety of physical and neurocognitive disorders caused by prenatal alcohol exposure. Although their overall prevalence is around 0.77%, FASD remains underdiagnosed and little known, partly due to the complexity of their diagnosis, which shares some symptoms with other pathologies such as autism spectrum, depression or hyperactivity disorders.
METHODS
This study included 73 control and 158 patients diagnosed with FASD. Variables selected were based on IOM classification from 2016, including sociodemographic, clinical, and psychological characteristics. Statistical analysis included Kruskal-Wallis test for quantitative factors, Chi-square test for qualitative variables, and Machine Learning (ML) algorithms for predictions.
RESULTS
This study explores the application ML in diagnosing FASD and its subtypes: Fetal Alcohol Syndrome (FAS), partial FAS (pFAS), and Alcohol-Related Neurodevelopmental Disorder (ARND). ML constructed a profile for FASD based on socio-demographic, clinical, and psychological data from children with FASD compared to a control group. Random Forest (RF) model was the most efficient for predicting FASD, achieving the highest metrics in accuracy (0.92), precision (0.96), sensitivity (0.92), F1 Score (0.94), specificity (0.92), and AUC (0.92). For FAS, XGBoost model obtained the highest accuracy (0.94), precision (0.91), sensitivity (0.91), F1 Score (0.91), specificity (0.96), and AUC (0.93). In the case of pFAS, RF model showed its effectiveness, with high levels of accuracy (0.90), precision (0.86), sensitivity (0.96), F1 Score (0.91), specificity (0.83), and AUC (0.90). For ARND, RF model obtained the best levels of accuracy (0.87), precision (0.76), sensitivity (0.93), F1 Score (0.84), specificity (0.83), and AUC (0.88). Our study identified key variables for efficient FASD screening, including traditional clinical characteristics like maternal alcohol consumption, lip-philtrum, microcephaly, height and weight impairment, as well as neuropsychological variables such as the Working Memory Index (WMI), aggressive behavior, IQ, somatic complaints, and depressive problems.
DISCUSSION
Our findings emphasize the importance of ML analyses for early diagnoses of FASD, allowing a better understanding of FASD subtypes to potentially improve clinical practice and avoid misdiagnosis.
PubMed: 38808031
DOI: 10.3389/fnins.2024.1400933 -
Frontiers in Nephrology 2024Congenital nephrotic syndrome (CNS) is a severe kidney disorder characterized by edema, massive proteinuria, and hypoalbuminemia that manifests or within three months...
BACKGROUND
Congenital nephrotic syndrome (CNS) is a severe kidney disorder characterized by edema, massive proteinuria, and hypoalbuminemia that manifests or within three months after birth. CNS affects 1-3 per 100,000 children, primarily associated with genetic variants and occasionally with infections. Genetic analysis is the first-line method for diagnosis. The most common founder variants have been identified in European populations, often resulting in end-stage kidney disease by 1-2 years of age.
CASE-DIAGNOSIS/TREATMENT
A female full-term neonate, without prenatal signs of kidney disease, was admitted to Rapa Nui (Eastern Island) Hospital at the age of 2 months due to bronchial obstruction. She presented fever, oliguria, edema, urine protein-to-creatinine ratio (UPCR) 433.33, and hypoalbuminemia (0.9 g/dL). She was transferred to a mainland Chilean hospital following CNS diagnosis. Viral screening detected cytomegalovirus (CMV) positivity in both blood and urine. A kidney biopsy revealed interstitial nephritis and diffuse podocyte damage and the tissue PCR resulted negative for CMV. Interviews with the parents revealed consanguinity, suggestive of hereditary CNS. Genetic analysis identified the Maori founder variant, c.2131C>A (p.R711S), in homozygosis. The patient received albumin infusions and antiviral therapy, being discharged when she was 5 months old, with improved laboratory parameters evidenced by UPCR 28.55, albumin 2.5 g/dL, and cholesterol 190 mg/dL. Subsequent clinical monitoring was conducted through virtual and in-person consultations. At her last follow-up at 4 years 2 months old, she presented UPCR 16.1, albumin 3.3 g/dl and cholesterol 220 mg/dL, maintaining normal kidney function and adequate growth.
CONCLUSIONS
To our knowledge, this represents the first case of CNS in Chile carrying a variant associated with prolonged kidney survival. As described in the Maori population, the patient exhibited a less severe clinical course compared to classical patients. Genetic testing for the Maori founder variant in CNS patients related to the New Zealand population, could impact management decisions and potentially prevent the need for nephrectomies.
PubMed: 38808020
DOI: 10.3389/fneph.2024.1379061