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IMF-069-02-0001-en	Why is an affected relative usually tested before an unaffected relative who is concerned about risk?	If the familial variant is unknown, a negative result in an unaffected person is uninformative, whereas a clear phenotype gives testing the best chance of finding the cause.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0002-en	How can a family history conceal a genetic syndrome, and what helps clarify it?	Small families, preventive surgery, death before expected onset and inaccurate labels hide it; pathology reports and medical records show whether family diseases truly match.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0003-en	When do minor anomalies make a syndrome more plausible rather than reflecting normal variation?	When several form a coherent developmental pattern or accompany a major malformation, growth difference, intellectual disability or organ-specific disease.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0004-en	What can chromosomal microarray detect that karyotyping cannot, and what does it generally miss?	It detects submicroscopic copy-number change across the genome, but generally misses balanced translocations, small sequence variants and some forms of mosaicism.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0005-en	Why can a negative genome sequencing result still miss the causal variant?	Sequencing does not automatically detect every repeat expansion, methylation defect, low-level mosaicism, mitochondrial variant or technically difficult region.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0006-en	In a suspected inborn error of metabolism, why take critical samples during illness, yet not delay treatment to get them?	Sampling after dextrose, dialysis, transfusion or recovery may reduce diagnostic yield, but acute stabilisation must not wait for diagnosis.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0007-en	What distinguishes a variant's pathogenicity from its causality for the current patient?	A variant can be genuinely pathogenic yet unrelated to the present illness; causality also needs matching mechanism, zygosity fitting inheritance and concordant phenotype.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0008-en	Why does failure of a variant to segregate in a family not automatically disprove causality?	Non-segregation may reflect reduced penetrance, phenocopy, incorrect diagnosis or technical error.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0009-en	Why should a variant of uncertain significance not be used for predictive testing of unaffected relatives?	It has not been shown to be the familial cause, so results would be misleading; carefully chosen family studies and later reanalysis may reclassify it instead.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0010-en	When is a negative genetic result a true negative, and why is it otherwise often uninformative?	Only when a known familial pathogenic variant is absent on an appropriate assay; otherwise the hypothesis, assay range, tissue, interacting variants or undiscovered genes may explain it.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0011-en	Why does broad hereditary cancer testing sometimes create management uncertainty?	It can reveal moderate-risk genes whose management evidence is less certain than that for high-penetrance syndromes.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0012-en	Why does a negative gene panel not end clinical surveillance in a strongly affected family with inherited cardiac disease?	The phenotype can be silent and age-dependent, and a negative panel does not exclude a genetic cause, so clinical tests such as electrocardiography and imaging continue.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0013-en	Why is cell-free DNA a screening rather than diagnostic test in pregnancy?	It estimates probability for selected chromosome conditions and is affected by placental mosaicism, maternal variants, malignancy, vanished twin and low fetal fraction.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending
IMF-069-02-0014-en	Why should children generally not have predictive testing for adult-onset conditions?	Such testing offers no childhood benefit, so it is not justified in childhood; any exception requires careful ethical analysis.	Integrated Medical Foundations; chapter 69, TTS module 2; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 5b3c27d01f451a23e3e6ff6686d7f0e95d3655f06f474cb021a4bc3f757bbb65; editorial review pending	imf lang::en chapter::069 module::069-02 review::pending