Neonatal Genomic Screening
Genomic newborn screening can extend targeted biochemical assays with whole-genome analysis. Review then begins with millions of variants, limited phenotype information, and time-sensitive clinical questions.
Under 60 minutes
Full genome interpretation
No phenotype required
Pathogenicity-first analysis
The Neonatal Interpretation Challenge
Neonatal intensive care combines short decision windows, incomplete phenotypes, and a broad diagnostic scope.
Time-Critical Decisions
In neonatal intensive care, variant review may need to inform time-sensitive decisions for presentations such as unexplained seizures or metabolic crisis.
Non-Specific Presentations
Newborns present with non-specific symptoms - respiratory distress, hypotonia, seizures, metabolic acidosis. These presentations overlap across hundreds of genetic conditions, making phenotype-guided gene panel selection unreliable.
Evolving Clinical Picture
A newborn's phenotype changes rapidly in the first days and weeks of life. Features that could narrow the differential diagnosis may not yet be apparent. Interpretation must work with incomplete and evolving clinical information.
Genome-Wide Scope
Targeted gene panels risk missing diagnoses outside their scope. For critically ill neonates, whole genome or exome analysis is increasingly the first-line approach - but it produces millions of variants that need systematic evaluation.
Phenotype-Agnostic Analysis
When a neonatal phenotype is incomplete, Folklore first ranks variants by pathogenicity evidence and then adds phenotype relevance as clinical information becomes available.
No Phenotype Required to Start
Folklore performs genome-wide pathogenicity-first prioritization. Every variant is classified and scored based on population frequency, functional predictions, gene constraint, and clinical databases - independent of phenotypic input. When HPO terms are available, phenotype matching adds a correlation layer. When they are not yet available (common in NICU), the system still produces a clinically useful prioritized variant list.
Phenotype Matching as Evolving Layer
As the newborn's clinical picture develops, HPO terms can be updated and the case reprocessed. New phenotype information immediately re-ranks variants based on genotype-phenotype correlation, surfacing candidates that were classified but not initially prioritized. The underlying classification does not change - only the clinical prioritization adapts.
Unexpected Diagnoses Surface
Phenotype-agnostic review retains pathogenic and likely pathogenic variants in genes outside the initial differential diagnosis. This matters when the neonatal presentation is broad or involves several systems.
Age-Aware Screening Profiles
Variant prioritization adapts to the clinical context. A newborn in the NICU and a child in a developmental genetics clinic have different urgent gene lists and different clinical priorities.
Neonatal
0 - 28 daysHighest priority for conditions with neonatal onset and available treatment. Gene weighting emphasizes disorders where early intervention changes outcomes - metabolic conditions (PKU, galactosemia, MCAD deficiency), cystic fibrosis, spinal muscular atrophy, congenital adrenal hyperplasia, and early-onset epilepsies.
Key genes: CFTR, SMN1, GAA, GBA, HEXA, PAH, GALT, ACADM, CYP21A2, and curated neonatal-onset gene lists
Pediatric
29 days - 18 yearsBroader scope including childhood-onset conditions. Weight profiles shift toward developmental disorders, childhood-onset metabolic conditions, immunodeficiencies, and genetic epilepsies. Lower urgency than neonatal but still requires efficient evidence gathering for timely clinical decisions.
Key genes: Expanded panels including developmental delay, intellectual disability, epilepsy, and immunodeficiency gene lists
Proactive
Any agePopulation-scale screening for actionable genetic conditions regardless of current clinical presentation. Focuses on conditions where early knowledge enables preventive action - hereditary cancer syndromes, cardiac conditions (LQTS, HCM), pharmacogenomic variants, and carrier status.
Key genes: ACMG SF v3.2 secondary findings list, pharmacogenomic panels, carrier screening panels
Platform Capabilities
Processing Speed
Gene panel VCF: 1-2 minutes. Whole exome: 2-5 minutes. Whole genome: under 15 minutes. Classification, annotation, and phenotype matching run in parallel across the full variant set.
Neonatal Gene Curation
Age-aware scoring profiles weight neonatal-onset conditions with available treatment higher than adult-onset conditions. Gene lists are curated from OMIM, GeneReviews, and newborn screening program publications.
ACMG Classification
Each variant receives ACMG/AMP classification under the Bayesian point framework. The geneticist can inspect the evidence recorded for each finding.
Tiered Clinical Output
Results are presented in clinical tiers: Tier 1 for findings requiring immediate review, Tier 2 for findings requiring further evaluation, and a separate incidental-findings group.
Reprocessing Without Re-Upload
As clinical information evolves, cases can be reprocessed with updated HPO terms or different screening profiles without re-uploading the VCF. Updated reference databases are applied automatically, and previous results are preserved for comparison.
GDPR-Native EU Infrastructure
Neonatal genomic data is among the most sensitive categories of personal data. All processing occurs on dedicated infrastructure in Helsinki, Finland. No variant data leaves the EU. No external API calls are made during analysis.
See Neonatal Screening in Action
Trace a neonatal case from whole-genome VCF to age-aware clinical prioritization.