ArticleHuman genomics2026
Genetic architecture and prognostic significance of suspected fetal microcephaly: evidence from prenatal exome sequencing in a large prospective cohort.
Article in Human genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
backgroundFetal microcephaly (FMIC) is a neurodevelopmental disorder with heterogeneous etiologies and uncertain prenatal prognosis. Discrepancies between prenatal and postnatal head circumference (HC) measurements may confound ultrasound-based diagnosis, underscoring the need for genetic stratification to improve risk assessment.
methodsThis prospective cohort study analyzed data from 301 fetuses with suspected FMIC collected between 2014 and 2022. Trio-prenatal exome sequencing (pES) was performed in 301 fetuses with suspected FMIC and normal results on karyotyping and chromosomal microarray analysis. Diagnostic yield, molecular spectrum, and pathway enrichment were analyzed. Clinical follow-up was conducted to correlate genetic findings with postnatal neurodevelopmental outcomes.
resultsMolecular diagnoses were achieved in 41 cases (13.6%). Diagnostic yield was significantly higher in complex FMIC compared with isolated FMIC (15.9% vs. 10.1%, p < 0.01), and peaked in cases with family history (26.7%). Our findings expand the prenatal phenotypic spectrum for six genes (TUBB2A, DUOX2, EBP, FAM111A, FGFR3, PEX1), indicating that microcephaly can be a primary presenting feature in the fetus for conditions where it was previously considered a secondary or postnatal finding. Pathogenic variants were enriched in neurogenesis and extracellular matrix-related pathways, implicating dysregulated cell cycle progression and synaptogenesis. Importantly, HC standard deviation (HC-SD) correlated with diagnostic yield and, as demonstrated by multivariable analysis, served as an independent predictor of postnatal prognosis (aOR: 2.1 per 1-SD decrease; 95% CI: 1.5-3.0), whereas fetal growth restriction appeared nonspecific.
conclusionsThis prospective cohort study provides the largest prenatal genomic and prognostic analysis of FMIC to date, revealing potential genotype-phenotype associations, pathogenic pathways, and prognostic markers. These findings enhance understanding of FMIC mechanisms and provide essential evidence for prenatal genetic counseling and individualized risk assessment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.