Prenatal Diagnosis最新文献

Objective: To present prenatal sonographic features, genomic results, and pregnancy outcomes of fetuses with KBG syndrome (KBGS).

Method: This was a retrospective study of 12 cases with KBGS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected for these cases, including maternal demographics, prenatal sonographic findings, molecular test results, and pregnancy outcomes.

Results: Twelve cases of KBGS were diagnosed prenatally with confirmatory genetic testing. Five had an abnormal first-trimester ultrasound with increased nuchal translucency (NT). Seven cases had a normal first-trimester ultrasound. Among these, four had mild ventriculomegaly in the second or third trimester, one had an arachnoid cyst found at 22 weeks, one had umbilical-systemic shunt, ventriculomegaly and polyhydramnios found at 24 weeks, and one presented with fetal growth restriction at 30 weeks. Four pregnancies continued to term, and infants presented with the classic phenotype of KBGS at a follow-up of 12 months. All ANKRD11 alterations in the 12 cases were de novo, and were characterized as either deletions encompassing ANKRD11 or loss-of-function variants.

Conclusion: Increased NT and mild ventriculomegaly are two common sonographic features of fetal KBGS. Prenatal diagnosis of KBGS can be achieved with ultrasound and comprehensive molecular testing.

Shwachman-Diamond Syndrome (SDS) is a rare genetic disorder with pancreatic insufficiency, bone marrow failure, and skeletal abnormalities. Prenatal diagnosis is rare, with only one previous case. We report a novel antenatal SDS diagnosis at 22 weeks gestation. Ultrasound showed mildly straightened fetal ribs without significant shortening. Whole exome sequencing identified pathogenic variants in the SBDS gene, confirming SDS. This highlights the importance of subtle rib anomalies in prenatal ultrasound for SDS detection. It expands the prenatal phenotypic spectrum and emphasizes the need for further research. Genetic diagnosis is crucial for counseling, pregnancy management, and recurrence risk assessment.

Objective: To receive feedback on the design and content of a prenatal genetics video tool and explore pregnant patients' views on genetic information privacy.

Methods: Video education covered prenatal aneuploidy screening and diagnosis and genetic privacy of cell-free DNA (cfDNA). English or Spanish-speaking adult patients, presenting for pregnancy dating ultrasound at a health center or clinic were eligible to answer a demographic questionnaire and view video education. Virtual, in-depth semi-structured interviews were then performed. Thematic analysis of transcripts was performed; all were double coded.

Results: Twenty participants completed interviews, achieving data saturation.

Demographics: median age 30.5 years, 50% Spanish-speaking, 55% White, 60% Hispanic, 65% had a high-school degree or less, 60% parous. Themes: The intervention was acceptable, accessible, and aided in decision-making. Tangible adjunctive resources were desired. Content misunderstandings included absolute risk of diagnostic testing and perception of aneuploidy as hereditary. Genetic privacy played a minor role in decision-making. Participants were amenable to data-sharing with third parties, but wanted to be informed. They misunderstood that genetic data could never truly be de-identified. No differences were found in opinions on sharing fetal versus maternal data or with academic versus private institutions.

Conclusion: Video education was acceptable and comprehensible, yet participants showed limited awareness of cfDNA privacy implications.

We report a case of a fetus with a congenital paraesophageal hernia (CPEH) with suspected volvulus and a paternal history of Marfan syndrome (MFS). The patient was followed by a multidisciplinary team with plans for postnatal surgical intervention and genetic testing. Postnatal examination confirmed CPEH with gastric volvulus, requiring surgical repair on the first day of life. Neonatal genetic analysis detected a paternally inherited heterozygous pathogenic variant in FBN1, associated with MFS. Prenatal ultrasound findings of CPEH and volvulus have seldom been reported as associations with fetal MFS. This case highlights a rare association and the importance of proactive planning and early surgical intervention.

We report a case of a male fetus with early-onset macrosomia and a pathogenic variant in PTEN identified on a macrocephaly and overgrowth sequencing panel. The pregnancy ended at 25 weeks gestation. On post-mortem examination, macrosomia was confirmed, and maturation of the brain was approximately 3 weeks ahead of that of the visceral organs. There was microscopic evidence of gonadoblastoid dysplasia, which is an extremely rare finding and has never been associated with PTEN hamartoma tumor syndrome (PHTS). To our knowledge, this is the first report of a prenatal phenotype with a heterozygous germline variant in PTEN.

Introduction: Genome-wide non-invasive prenatal testing (gwNIPT) has screening limitations for detectable chromosomal conditions and cannot detect microdeletions/microduplications (MD) or triploidy. Thickened nuchal translucency (NT) only detects around 10% of these cases.

Methods: A 4-year retrospective study of singleton pregnancies undergoing first-line gwNIPT screening with subsequent CVS or amniocentesis. All MD cases, with or without gwNIPT screening, were also analyzed.

Results: Among 919 pregnancies with gwNIPT and invasive testing, 338 had a single chromosomal abnormality, with 9 false negative gwNIPT results (2.9%) and 26 undetectable abnormalities (18 MD, 8 triploidy) (7.7%). Twelve cases had a dual chromosomal abnormality and 4 returned a low-risk gwNIPT result. Only three (9%) of the "missed cases" had a large NT and two of these also had a structural abnormality. Approximately 90% of chromosomal anomalies missed by gwNIPT were detected by invasive prenatal testing indicated by one or more of the following: failed NIPT (9%), low PAPP-A (12%), early growth restriction (37%) and structural anomalies at pre-NIPT, 13- or 20-week ultrasounds (51%).

Conclusion: Most chromosomal abnormalities missed or unable to be found by gwNIPT are detected due to growth restriction or structural anomalies, not an enlarged NT. Failed NIPT and low PAPP-A concentrations contributed to detection.

Objective: Our objective was to investigate prenatal imaging findings, clinical course and outcomes associated with isolated congenital aqueductal stenosis (ICAS).

Method: A retrospective study was conducted in the period of 2010-2023, including patients with ICAS confirmed postnatally who were imaged prenatally with ≥ 1 year of follow-up. Patients with additional anomalies (structural or genetic) were excluded. Neurodevelopmental outcomes were verified by pediatricians, and imaging underwent standardized measurement by a neuroradiologist.

Results: Twenty-one patients were prenatally diagnosed with ICAS, at a median gestational age (GA) of 19.7 weeks. Overall, 13/14 patients exhibited a fronto-occipital horn ratio (FOHR) > 0.5, indicating clinically significant ventriculomegaly in initial MRI at 18-32 weeks GA. There was an increase in the median size of the third ventricular coronal width from 7 mm in prenatal imaging to 12 mm in postnatal imaging (p = 0.01). Twenty patients (95.2%) required shunting or endoscopic third ventriculostomy and bilateral choroid plexus cauterization (ETV/CPC), with 10 undergoing multiple CSF diversion procedures during follow-up. Among the study group, nine patients experienced epilepsy, 6/8 aged < 5 years exhibited global developmental delay, and 6/12 aged ≥ 5 years required special education services.

Conclusion: Our findings indicate a progressive increase in prenatal ventricular sizes, with most children requiring hydrocephalus treatment and experiencing neurodevelopmental impairment.

Objective: To correlate ultrasound findings with fetoscopy and pathology data in patients with suspected congenital high airway obstruction syndrome (CHAOS) to improve prenatal diagnosis and management.

Method: This study included five consecutive patients suspected of having CHAOS. Prenatal ultrasound was performed to identify key features such as bilateral hyperechoic lungs, eversion of the diaphragm, and visible airways. Fetoscopy was conducted in three patients to assess the vocal cords and upper airways. Pathological analysis was also used to confirm the diagnosis.

Results: All five patients showed bilateral hyperechoic lungs, eversion of the diaphragm, and visible airways on ultrasound. An obstructive block was seen in all cases and the vocal cords were not visualized in three cases, abnormal in one case and not mentioned in one case. Fetoscopy confirmed vocal cord fusion or absence and complete laryngeal atresia in three patients. All pregnancies were terminated; therefore, medium-term complications of fetoscopy could not be assessed.

Conclusion: Accurate prenatal ultrasound imaging is essential for diagnosing CHAOS and determining prognosis. While ultrasound is the first-line test to assess the condition and guide management, fetoscopy should only be proposed when ultrasound findings are inconclusive. The diagnostic and therapeutic value of fetoscopy is limited to cases with nonvisible vocal cords and obstructive laryngeal block.

Objective: To investigate the performance of targeted gene sequencing, expanded gene panels, and selected exomes for prenatally identified fetal anomalies, after non-diagnostic microarray results.

Method: All fetal samples received for genetic testing for fetal structural anomalies in the Canadian Maritime Provinces (2014-2022) were identified. Utilization and results of NGS sequencing strategies after a non-diagnostic microarray were correlated with ultrasound findings and autopsy results.

Results: Five hundred and ninety-three cases of fetal anomalies with non-diagnostic RAD results were identified, including 319 (54%) with isolated anomalies. Diagnostic yield from the microarray was 7.5%. Sequence-based testing for 131 cases gave an overall diagnostic yield of 38% (8.4% of initial cohort). For isolated anomalies, diagnostic yield was highest in the intracranial, renal, and musculoskeletal systems (44%, 60%, 64% respectively). Appropriate targeted gene sequencing provided a diagnostic yield of 40%. With clinically indicated criteria for exome analysis, diagnostic yields were higher than when clinical information prompted use of a selected gene panel (73% vs. 27%). Expanding to an exome after a non-diagnostic gene panel had an additional diagnostic yield of 13%.

Conclusion: Multidisciplinary review and comprehensive clinical information can inform the selection of strategies for expanded genetic testing after non-diagnostic microarray for fetal anomalies within a publicly funded health care system.

Objective: To investigate the current genetic counseling practices involving a cfDNA result indicating mosaic monosomy X of likely maternal origin, and to better understand the perspectives of patients who have received this result.

Method: A total of 60 prenatal genetic counselors completed surveys about their experiences with this result, cfDNA consenting practices, and management practices. In addition, qualitative interviews were conducted with 5 patients to gain insight into their experiences with result disclosure and follow-up care.

Results: 95% of genetic counselors reported feeling prepared to counsel on these results. However, responses to current practices varied. Of the genetic counselors surveyed, 62% state that their approach to management does not differ if the patient is symptomatic. Responses indicated 95% of genetic counselors ordered a karyotype for maternal diagnostic testing, and 30% ordered a chromosomal microarray. Interviews of patients found that 100% were not aware of the possibility of receiving an incidental finding from cfDNA. Patients reported feeling surprised, confused, and worried when they received their results.

Conclusion: The majority of genetic counselors report feeling confident in counseling these results, but their current practices vary. Patients who receive these results are found to have a difficult time adapting due to feeling surprised and confused. Based on these findings, we believe professional practice guidelines are needed to establish clear management recommendations, which in turn would hopefully decrease patient and provider stress.