Prenatal Diagnosis最新文献

Background: Chondrodysplasia punctata 1 (CDPX1) is an X-linked recessive disorder of cartilage and bone development characterized by stippling on the cartilage and bone, flattened nasal bridge, and brachydactyly, or short fingers. CDPX1 has been associated with variants in the ARSL gene and is known to manifest prenatally, however, there has been no systematic literature review on this evidence.

Aims: Here, we reviewed the current literature on prenatal manifestations of CDPX1, and additionally introduce previously unpublished cases.

Materials & methods: A systematic review of the literature was performed. Additionally, a GeneMatcher submission was created and a call for cases was presented at the Fetal Sequencing Consortium meetings to find previously unpublished cases.

Results: For the 22 fetuses reported here, we found that 55% had nasal hypoplasia, 41% had bony stippling or calcifications, 32% had polyhydramnios, 5% had oligohydramnios, 23% had shortened long bones, 23% had spinal canal stenosis, 18% had ventriculomegaly, 9% had brachydactyly/brachytelephalangy, 9% had clubbed feet, 9% had premature rupture of membranes, and 9% had intraventricular hemorrhage detected through sonography or radiography. We also found 17 unique variants in ARSL for these 22 fetuses.

Discussion: A previously unpublished association of ARSL variants with intrauterine fetal death or stillbirth has been noted in this study. It is also possible that intracranial hemorrhage is an underrecognized feature associated with CDPX1 variation. However, there have been challenges in applying ACMG criteria to ARSL, a gene without an associated Variant Curation Expert Panel.

Conclusion: This literature review and case series highlights which features of CDPX1 manifest prenatally, as well as introduces new phenotypes that have not been previously identified.

Objective: This study aims to elucidate two distinct fetal ultrasound features associated with aberrant brain sulcus formation as potential prenatal markers for Sotos syndrome caused by mutations in the NSD1 gene.

Method: This retrospective study investigated three fetuses across two pregnancies, including a pair of monochorionic diamniotic twins, all diagnosed with Sotos syndrome via whole exome sequencing (WES). Comprehensive clinical and laboratory data were collected and analyzed. Each fetus underwent a series of specialized neurosonographic assessments to evaluate the development of the cerebral cortex.

Results: All three fetuses exhibited aberrant brain sulcus formation characterized by Sylvian fissure (SF) abnormalities and shallow parietooccipital sulcus (POS). WES revealed the presence of two de novo NSD1 variants in these fetuses.

Conclusions: Fetal aberrant brain sulcus formation may represent a distinctive ultrasound feature indicative of Sotos syndrome, thereby offering additional diagnostic insights for the identification of this condition.

Objective: Providing accurate prenatal prognostication for expectant parents is challenging due to limited literature on factors impacting outcomes in children with congenital aqueductal stenosis (CAS). This study stratified CAS patients into isolated or complex categories (presence of additional intra- or extra-cranial anomalies or genetic syndromes) and evaluated both short- and long-term outcomes. Additionally, the role of ventricular rupture was assessed.

Methods: This was a single center retrospective-cohort study of CAS patients who underwent fetal MRI over a 10-year period.

Results: Of 140 patients with CAS, 107 (76%) were complex and 33 (24%) were isolated. There were no differences in the size of ventricular enlargement or incidence of ventricular rupture between the two groups. 14 pregnancies were terminated, 9 experienced fetal demise/stillbirth, and there were 21 post-natal deaths. Outcomes at the time of hospital discharge were available for 86 patients and long-term follow-up data for 64. CSF diversion (via ventriculoperitoneal shunt) was performed in 95% of complex and 71% of isolated CAS patients. Acutely, no differences were noted in seizures (complex: 10%; isolated: 18%) or respiratory support but there was an increased risk for feeding support. Risks for non-ambulatory status (complex: 32% vs. isolated: 0%), epilepsy (complex: 56% vs. isolated: 19%) and long-term gastrostomy tube assisted feeding (complex: 25.5% vs. isolated: 0%) were significantly greater with complex CAS. The presence of rupture did not impact clinical outcome.

Conclusion: Poor clinical outcome was associated with complex CAS. Ventricular rupture alone did not portend a poor outcome. Prenatal counseling can tailor prognostication by CAS type.

Prenatal exposure to alcohol (PAE) can impact short- and long-term offspring health. However, knowledge on PAE and brain development in early life is limited. This systematic review investigated associations between PAE and brain development during the first 1000 days of life, and was registered in PROSPERO at CRD42022355144. The literature search was performed from inception until February 2024 in EMBASE, MEDLINE, Web of Science, PsycINFO, and the Cochrane Library. Studies investigating PAE and brain development during the first 1000 days using ultrasound, magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI) were included. Our search initially identified 3618 articles, of which 16 were included. The findings suggest inconsistent associations between PAE and early brain development. Ultrasound studies on PAE and brain size report no clear relationship. Some postnatal MRI studies reported smaller thalami, amygdalae and hippocampi in alcohol exposed neonates. Postnatal DTI studies (n = 5) examining network integrity and connectivity reported bidirectional results in multiple brain networks. Our results highlight the need for further research on first trimester brain development, timing and quantity of alcohol exposure using a core set of validated instruments. Longitudinal assessments and standardized procedures for neuroimaging are crucial to understand the impact of PAE on early brain development.

Purpose: MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant.

Methods: Detailed radiographic, pathological, clinical, and molecular data from 12 prenatal cases were collected through an international collaborative study. Adding the five fetuses previously published, we were able to study a cohort of 17 cases.

Results: Main ultrasound-accessible manifestations of MYRF-CUGS include congenital heart defects (13/17, 76%), congenital diaphragmatic hernia (10/17, 59%) and disorders of sexual differentiation in 46, XY fetuses (7/14; 50%). Postnatal examination and/or autopsy data highlighted additional birth defects and neurological findings with a large spectrum of severity. Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants).

Conclusion: We report the first prenatal cohort of MYRF-CUGS, allowing us to further characterize the variable expressivity of this rare disorder in fetuses. Severe congenital anomalies with a poor prognosis are more frequent than previously described in postnatal cases. Our data suggest that MYRF-CUGS is characterized by a recurrent recognizable malformative association, accessible to prenatal diagnosis, with a significant intrafamilial phenotypic variability making genetic counseling challenging.

Objective: To describe (1) procedure-related complications, and (2) gestational age (GA) at delivery in patients who received their final intrauterine transfusion (IUT) at ≥ 34 weeks 0 days versus at < 34 weeks 0 days.

Methods: This was a retrospective study of pregnancies treated with IUT. Procedure-related complications were defined as any of the following within 48 h of IUT: (1) rupture of membranes or preterm delivery, (2) intrauterine infection, (3) fetal death, (4) fetal compromise resulting in emergency cesarean, or (5) neonatal death. Patient and procedural characteristics were described among patients with final IUT at ≥ 34 weeks 0 days and at < 34 weeks 0 days.

Results: We studied 94 pregnancies with 237 IUTs; 35 (37.2%) had their last IUT at ≥ 34 weeks 0 days and 59 (62.8%) had their last IUT at < 34 weeks 0 days. Three procedure-related complications occurred (1.3% of procedures, 3.2% of pregnancies). All resulted in emergency cesarean section; 1 case performed at < 34 weeks 0 days resulted in neonatal death. The remaining 2 occurred during IUT at ≥ 34 weeks 0 days. Pregnancies with the last IUT at ≥ 34 weeks 0 days delivered at a median GA of 37.1 weeks.

Conclusions: Complications were rare. IUT performed at ≥ 34 weeks 0 days appeared safe.

Objective: To assess contemporary outcomes of fetuses who underwent open fetal spina bifida surgery in Canada.

Methods: Our clinical program prospectively collected outcomes of all consecutive fetuses who underwent open fetal spina bifida closure at the Ontario Fetal Center in Toronto and who were at least 1 year of age at the time of postnatal follow-up. We gathered information on the need for hydrocephalus treatment, motor function, bladder function, as well as neurodevelopment (Ages and Stages Questionnaire and Bayley's scales of infant development). Developmental outcomes were categorized as "Typical Development," "Possible Delay," or "Significantly Delayed."

Results: Between 2017 and 2022, 41 fetuses underwent open fetal spina bifida closure. Twenty-four patients (58.5%) responded to the questionnaire at a median age of 46.5 months. Eight children (33.3%) required CSF diversion procedures. Bladder management included clean intermittent catheterization (43.5%), spontaneous voiding (34.8%), or both (21.7%), with 43.5% needing medication for overactive bladder. All patients could sit independently, with 50% walking outside and 50% crawling indoors. Among those walking outdoors (50%), 25% did so without orthotics or aid, 58.3% with orthotics, and 16.7% required additional walking aids. Most children demonstrated typical communication and problem-solving skills (79.2%), while gross motor development was significantly delayed in 91.7% of cases. Fine motor skills varied, with 56.5% showing typical development and 34.8% possibly experiencing delays.

Conclusions: This study showed a mixed developmental profile among patients who underwent open fetal spina bifida repair, consistent with the MOMs trial findings.