Table 2. Werner syndrome diagnostic confidence categories.

Diagnostic category	Sensitivity analysis category	Diagnostic criteria
Definite	High confidence	all cardinal signs + two additional signs OR confirmed pathogenic mutations in both WRN alleles
Probable	High confidence	first 3 cardinal signs + any 2 others
Possible	Low confidence	either cataracts or dermatological changes + any 4 additional signs
Exclusion**	Exclude	Onset of signs or symptoms before adolescence (except stature)

Diagnostic criteria and categorization notes:

^*WS diagnostic confidence categories were taken from the International Registry of Werner Syndrome: www.wernersyndrome.org/registry/diagnostic.html with the following modifications: 1. putative WS patients with known pathogenic mutations in both WRN alleles were also considered to be ‘Definite’/‘High confidence’; and 2. “mesenchymal neoplasms, rare neoplasms or multiple neoplasm” was not counted for any of the patients in the determination of Werner syndrome diagnostic confidence.

^**We had no case exclusions based on the onset of signs or symptoms prior to adolescence. Two Japan-resident cases were reported with voice changes prior to adolescence, and one Japan non-resident case was reported to have had premature greying of the hair at age 8 (see Table S1).