Diagnostic Genetics & Monogenic Primary Care
Diagnostic genetics is not a lab test you order — it's a clinical process. OriginalDx provides the physician expertise to select the right test, interpret the results, and act on them.
What We Test
Exome Sequencing (ES)
Sequences the protein-coding regions of the genome. First-line test for most suspected monogenic conditions. 27–92% diagnostic yield depending on indication.
Genome Sequencing (GS)
Comprehensive sequencing including non-coding regions and structural variants. Used when exome is non-diagnostic or when structural variants are suspected.
Targeted Gene Panels
Indication-specific panels for well-defined phenotypes. Faster turnaround, focused interpretation. Used when the clinical picture points to a specific gene group.
Rapid ES/GS
3–7 day turnaround for critically ill patients in NICU and PICU settings. Diagnosis within the admission.
RNA Sequencing
Functional analysis for cases where ES/GS identifies variants of uncertain significance or is non-diagnostic. Detects aberrant splicing and expression.
Chromosomal Microarray
Detects copy number variants (deletions, duplications). First-line for developmental delay, intellectual disability, and congenital anomalies.
When We Test
Genetic testing is appropriate when the clinical picture suggests a monogenic cause. Common scenarios include:
- Suspected monogenic disease — a clinical presentation consistent with a single-gene disorder
- Undiagnosed disease with genetic features — multiple organ involvement, consanguinity, family history
- Family history of a known genetic condition — cascade testing, carrier screening
- Pharmacogenomic optimization — medication selection guided by genotype
- Reanalysis — periodic re-review of prior exome/genome data as variant databases grow
The CarePathway Model
At OriginalDx, genetic testing is delivered through structured CarePathways — clinical pathways that bundle the entire diagnostic process into a single care episode:
Clinical Assessment
Comprehensive evaluation of the patient's presentation, family history, and prior workup to determine the appropriate testing strategy.
Test Selection & Authorization
Selection of the right test for the clinical question. Prior authorization submitted to the patient's insurance.
Interpretation
Results interpreted by a board-certified medical geneticist — not just reported. Clinical significance assessed in the context of the patient's phenotype.
Result Disclosure
Face-to-face discussion of results, what they mean, and what changes in the patient's care going forward.
Follow-Up Care
For patients with a confirmed diagnosis, transition to longitudinal primary care built around the genetic condition.
Diagnostic Yield by Organ System
Published diagnostic yield data across 20 organ systems, supported by 80 peer-reviewed references.
Tier 1: Strong Evidence 18 Systems
| Organ System | Diagnostic Yield | Indications | Key Conditions |
|---|---|---|---|
| Dermatologic | 58–95% | 3 | Epidermolysis bullosa, genodermatoses, mosaic skin disorders |
| Metabolic/IEM | 88–90% | 5 | Inborn errors of metabolism, newborn screening confirmation, leukodystrophies |
| Musculoskeletal | 50–89% | 4 | Muscular dystrophies, myopathies, connective tissue disorders, arthrogryposis |
| Ophthalmic | 49–92% | 5 | Inherited retinal diseases, congenital cataracts, optic atrophy |
| Pulmonary | 47–80% | 3 | Primary ciliary dyskinesia, pulmonary fibrosis, pulmonary arterial hypertension |
| Nephrology | 46–81% | 5 | Alport syndrome, CAKUT, cystic kidney disease, tubulopathies, nephrolithiasis |
| Neurological | 43–58% | 5 | Epilepsy, neuropathy, ataxia, leukodystrophy, movement disorders |
| Skeletal | 42–69% | 4 | Skeletal dysplasias, craniosynostosis, osteogenesis imperfecta, short stature |
| Auditory/Hearing | 39–67% | 3 | Sensorineural hearing loss, syndromic deafness |
| Cardiovascular | 32–67% | 4 | Cardiomyopathies, arrhythmias, aortopathies, familial hypercholesterolemia |
| Endocrine | 28–59% | 3 | Disorders of sex development, congenital adrenal hyperplasia, monogenic diabetes |
| Developmental | 27–41% | 5 | Intellectual disability, autism spectrum, developmental delay, congenital anomalies |
| Gastrointestinal | 25–64% | 6 | Monogenic IBD, polyposis syndromes, pancreatitis, motility disorders |
| Hepatic | 25–60% | 4 | Neonatal cholestasis, intrahepatic cholestasis, genetic liver diseases |
| Immunologic | 15–79% | 4 | Primary immunodeficiencies, inborn errors of immunity |
| Connective Tissue | 17–18% | 5 | Hereditary aortopathies, Ehlers-Danlos syndromes, Marfan syndrome |
| Craniofacial | 15–84% | 5 | Craniosynostosis, cleft lip/palate, craniofacial syndromes |
| Lymphatic | 15–79% | 6 | Lymphatic malformations, hereditary lymphedema |
Tier 2: Emerging Evidence 2 Systems
| Organ System | Diagnostic Yield | Notes |
|---|---|---|
| Psychiatric/Behavioral | 9–57% | Highest in consanguineous populations; neurodevelopmental overlap |
| Reproductive | 1.5–60% | DSD yield high (60%); idiopathic male infertility yield low (1.5%) |
Rapid Sequencing: NICU & PICU
Rapid genomic sequencing in critically ill neonates and children delivers diagnosis within the admission — before the diagnostic odyssey begins.
NICU
25% length-of-stay reduction. Cost-effective (ICER <€9,000).
PICU / CICU
80% management change rate. Time to diagnosis halved.
Monogenic Primary Care
Diagnosis is not the endpoint — it's the beginning of a care relationship. For patients with confirmed monogenic conditions, OriginalDx provides longitudinal primary care built around the genetic diagnosis:
- Genotype-guided medication management — prescribing informed by the patient's specific variant and pharmacogenomic profile
- Condition-specific surveillance — monitoring protocols tailored to the natural history of the diagnosed condition
- Reproductive counseling & cascade testing — family planning guidance and testing for at-risk relatives
- Specialist coordination — the genetic diagnosis as the anchor for all subspecialty care
- Annual genomic review — periodic reanalysis as variant databases and clinical knowledge evolve