1.20 Screening, Surveillance, Treatment & Diagnostic Strategy Framework
Key Takeaways
- Domain 1C conditions are managed with a repeatable framework: phenotype recognition → right test tier → cascade relatives → surveillance matched to organ risk → treatment lever (diet, ERT, surgery thresholds, devices)
- Screening (NBS, carrier screening, cascade ECG/echo) differs from diagnostic testing; counselors must not conflate a screen-positive result with a confirmed diagnosis
- Surveillance interval and modality follow the catastrophic risk—aorta imaging for Marfan/LDS, ammonia sick-day plans for urea-cycle, CK/cardiac follow-up for DMD carriers, QTc/drug review for LQTS
- Treatment themes cluster: dietary/medical for IEMs, ERT/SRT for selected LSDs, gene/sequence-modifier therapies for SMA, and surgical/device therapy for aortopathy/arrhythmia syndromes
- Diagnostic strategy chooses karyotype/CMA/single-gene/panel/exome based on suspected mechanism, urgency, and whether a familial variant already exists for targeted testing
Last updated: August 2026
1.20 Screening, Surveillance, Treatment & Diagnostic Strategy Framework
Quick Answer: For any Domain 1C condition, run the same loop: (1) name the catastrophe to prevent, (2) choose screening vs diagnostic testing correctly, (3) cascade at-risk relatives, (4) assign organ-specific surveillance, (5) activate the disease’s treatment lever. The exam rewards next-step judgment more than trivia.
Sections 1.17–1.19 taught the diseases. This section teaches the operating system genetic counselors use across them—exactly how ABGC Domain 1 knowledge items on natural history, surveillance, treatment, and testing strategy hang together.
The Five-Step Domain 1C Loop
| Step | Question you answer aloud | Example |
|---|---|---|
| 1. Catastrophe | What kills or disables if missed? | Aortic dissection; hyperammonemic coma; FXS expansion; SMA respiratory failure |
| 2. Test role | Is this screen, diagnostic, predictive, or carrier testing? | NBS MCADD screen vs ACADM confirmation; FBN1 diagnostic vs cascade predictive |
| 3. Cascade | Who else shares risk now? | DMD maternal relatives; AD Marfan children/siblings; AR SMA partner testing |
| 4. Surveillance | Which organ, how often, what modality? | Echo for Marfan; ECG for LQTS; CK/cardio for DMD carriers; ovarian evaluation for FXPOI |
| 5. Lever | Diet, ERT, drug, device, surgery, gene therapy, supports? | Phe diet; Pompe ERT; SMA disease-modifying therapy; β-blocker/ICD; aortic surgery thresholds |
If a vignette asks for the “most appropriate next step,” map it onto this loop before picking an answer.
Screening vs Surveillance vs Diagnostic Testing
These words are not interchangeable on the CGC exam.
| Term | Definition for counseling | Domain 1C examples |
|---|---|---|
| Screening | Test offered to an asymptomatic or broad population to identify higher risk | Newborn screening for PKU/MCADD/galactosemia/SMA (jurisdiction-dependent); ethnicity-informed or universal carrier screening; cascade ECG in LQTS relatives |
| Surveillance | Scheduled monitoring after risk is known | Annual (or more frequent) aortic imaging in Marfan/LDS; timed developmental/cardiac follow-up in DMD; neurologic follow-up in premutation FXTAS risk |
| Diagnostic testing | Test to confirm/refute disease in a symptomatic person or fetus | GAA sequencing in hypotonic infant with cardiomyopathy; COL3A1 testing after arterial rupture; CMA/exome for syndromic DD |
| Predictive / presymptomatic | Testing an asymptomatic relative for a known familial variant | Adult child of Marfan proband; adolescent sibling of HCM proband (with assent/consent nuance) |
| Carrier testing | Detect heterozygotes for AR/XL reproductive risk | SMA SMN1 dosage with residual-risk counseling; Tay-Sachs enzyme/DNA; Fragile X for reproductive planning |
Hard rule: Do not counsel a newborn-screen positive as a final diagnosis. Say “screen positive—confirmatory metabolic/molecular testing is required,” then discuss interim safety measures (e.g., feeding changes, fasting avoidance) as directed by the metabolic team.
Surveillance Matrices You Should Be Able to Rebuild
Metabolic / Storage
| Condition | Surveillance / sick-day focus | Treatment lever |
|---|---|---|
| PKU | Phe levels, nutrition, neurodevelopment; preconception control for women | Diet ± BH4-responsive therapy / pegvaliase pathways |
| Galactosemia | Diet adherence, development, speech, ovarian function in females | Lactose/galactose restriction |
| Urea-cycle (OTC etc.) | Illness protocols, ammonia access plan, liver-transplant discussions in severe disease | Protein management, scavengers, dialysis acutely |
| Gaucher type 1 | Blood counts, visceral/bone assessments | ERT / SRT |
| Pompe | Motor/respiratory/cardiac metrics | ERT; early Rx critical in infantile form |
| MCADD | Growth, avoidance of fasting, emergency letter currency | Prevent crises with nutrition/glucose support |
Neuromuscular / Fragile X
| Condition | Surveillance focus | Treatment / support lever |
|---|---|---|
| DMD/BMD (+ carriers) | Steroid/era-specific motor care, respiratory, cardiac; carrier echo | Multidisciplinary supportive care; evolving molecular therapies—counsel as time-sensitive referrals |
| DM1 | ECG/arrhythmia, weakness, cataracts, endocrine | Supportive; family cascade for conduction disease |
| SMA | Respiratory/motor milestones; therapy response | Disease-modifying therapies; earlier better |
| FXS | Development, behavior, educational supports | Supportive therapies; cascade FMR1 testing |
| FXTAS / FXPOI | Neuro / reproductive endocrine follow-up | Symptom management; fertility planning |
Connective Tissue / Cardiovascular
| Condition | Surveillance focus | Treatment lever |
|---|---|---|
| Marfan / LDS | Serial aortic/arterial imaging; ophthalmology (Marfan) | Meds, activity limits, surgical thresholds |
| vEDS | BP control, emergency vascular plan, pregnancy planning | Avoidance of high-risk elective procedures without expertise |
| HCM | Echo/ECG, risk stratification for SCD | Meds, septal reduction selected, ICD selected |
| ARVC | Arrhythmia surveillance; exercise counseling | Meds/ICD; activity modification |
| LQTS | QTc, trigger avoidance, drug lists | β-blockers; ICD selected |
Diagnostic Strategy: Choosing the Right Test Tier
| Clinical suspicion | First-tier thinking |
|---|---|
| Suspected chromosomal/syndromic DD with malformations | Chromosomal microarray (± karyotype if balanced rearrangement/aneuploidy strongly suspected) |
| Classic single-gene phenotype with clear target (DMD, FBN1, FMR1 CGG) | Targeted gene/repeat assay first |
| Overlapping aortopathy (Marfan vs LDS vs vEDS) | Multigene aortopathy panel |
| Broad cardiomyopathy/arrhythmia differential | Condition-specific cardiac gene panel |
| Infantile metabolic crisis | Concurrent biochemical critical labs + targeted/gene panel per metabolic genetics |
| Nonspecific hypotonia/DD after CMA | Consider neuromuscular/metabolic panels or exome with phenotypes captured precisely |
| Known familial variant | Site-specific testing for relatives (cheaper, clearer) |
Urgency modifier: In neonatal hyperammonemia or infantile Pompe with respiratory failure, stabilize and treat empirically while confirmatory genetics are pending. Test selection must not delay rescue.
Treatment Themes as Exam Shortcuts
| Lever class | Conditions |
|---|---|
| Substrate/diet control | PKU, galactosemia, urea-cycle protein management, MCADD fasting avoidance |
| Enzyme / substrate reduction | Gaucher, Pompe (ERT); selected others |
| Gene dosage / splicing / gene therapy era | SMA (and evolving DMD molecular therapies—know to refer early) |
| Mechanical catastrophe prevention | Aortic surgery thresholds; ICD; β-blockers in LQTS/aortopathy |
| Reproductive risk tools | PGT/prenatal diagnosis after familial variant known; maternal PKU diet; FXPOI fertility planning |
Putting It Together: Four Exam-Style Scripts
- Screen-positive NBS for MCADD: Interim no-prolonged-fasting plan → confirmatory acylcarnitine/gene testing → parental counseling for AR recurrence → sibling evaluation → emergency letter.
- Mother of boy with DMD: Offer carrier testing → if positive, cardiac surveillance + reproductive options → discuss germline mosaicism if leukocyte negative → cascade maternal female relatives.
- Proband with LDS gene variant: Arterial imaging plan → cascade first-degree relatives → pregnancy/activity counseling → distinguish from Marfan management nuances.
- Woman with FMR1 premutation seeking fertility advice: FXPOI risk → reproductive timeline/endocrine referral → expansion risk education → offer testing to relatives of reproductive age.
Common Framework Traps
| Trap | Correction |
|---|---|
| Treating carrier screening as diagnostic testing | Carriers are usually healthy; risk is reproductive (except XL manifesting carriers, FXPOI/FXTAS, DMD cardiac risk) |
| Skipping cascade after a clear AD aortopathy/cardiomyopathy result | Relatives share up to 50% risk—silence is harmful |
| Assuming all EDS needs the same surveillance | vEDS ≠ hypermobile EDS |
| Quoting SMN1 carrier negative as zero risk | Explain [2+0] residual risk |
| Delaying metabolic rescue for perfect genotyping | Treat ammonia/hypoglycemia first |
Mastering this framework lets you answer Domain 1C items even when the rare disease name is unfamiliar: identify the catastrophe, pick the correct test role, cascade, surveil, and treat.
Test Your Knowledge
A newborn has an out-of-range MCADD newborn screen. Which next-step package best reflects correct screening-versus-diagnosis counseling?
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B
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D
Test Your Knowledge
After a pathogenic TGFBR2 variant is identified in a proband with hypertelorism and arterial tortuosity, what is the most appropriate relative-focused action?
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B
C
D
Test Your Knowledge
Which example correctly matches a Domain 1C treatment lever to the condition?
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B
C
D
Test Your Knowledge
A genetic counselor is choosing tests for a floppy infant with hypertrophic cardiomyopathy. Which strategy best fits the Domain 1C diagnostic framework?
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B
C
D