CONFIRM · NATURAL HISTORY
05What is the lifespan and multisystem spectrum?
The information currently shared by connected individuals and families was not collected through one standard assessment and cannot estimate prevalence. Missing information remains missing unless an adequate assessment is documented. Each comparison uses only the people whose available information can answer that question.
POPULATION / COMPARATOR
Who or what should be compared?
A prospectively enrolled confirmation cohort with fixed eligibility, common assessments, defined visit windows, direct record capture, molecular verification, and explicit comparison with the current community observations.
STUDY DESIGN
How could the question be tested?
Build prospective natural history across the same 15 clinical areas, with clear source labels, explicit information availability, molecular subgroup, age, sex, relatedness, additional findings, acquisition or loss status, and repeated clinically meaningful function. Report present n / adequately assessed N for every feature.
EVIDENCE GATE
What would support the proposed link?
the same definitions and assessment schedule are applied prospectively, reported counts reconcile to their stated denominators, record validation is explicit, and estimates remain stable in sensitivity analyses for age, documentation level, relatedness, molecular group, and missingness.
STOP RULE
What would weaken it?
unassessed is treated as absent, retrospective convenience samples are labeled prevalence, documentation level is ignored, reported counts do not reconcile to their stated denominators, or sparse cells create identification or unstable estimates.