Sex differences in symptom presentation and their impact on diagnostic accuracy in Werner syndrome

AimWhether sex differences exist in hereditary progeroid syndromes remains unclear. In this study, we investigated sex differences in patients with Werner syndrome (WS), a model of human aging, using patient data at the time of diagnosis.MethodsThe presence of six cardinal signs in the diagnostic criteria was retrospectively evaluated.ResultsWe found that the percentage of patients with all cardinal signs was higher in males than in females (54.2% vs. 21.2%). By the age of 40 years, 57.1% of male patients with WS presented with all the cardinal signs, whereas none of the female patients developed all of them. In particular, the frequency of having a high-pitched, hoarse voice, a characteristic of WS, was lower in female patients. The positive and negative predictive values for clinical diagnosis were 100% for males and females, indicating the helpfulness of diagnostic criteria regardless of sex. More female patients than male (86.7% vs. 64%) required genetic testing for their diagnosis because their clinical symptoms were insufficient, suggesting the importance of genetic testing for females even if they do not show typical symptoms of WS. Finally, the frequency of abnormal voice was lower in patients with WS harboring the c.3139-1G > C homozygous mutation.ConclusionThese results indicate, for the first time, that there are sex differences in the phenotypes of hereditary progeroid syndromes. The analysis of this mechanism in this human model of aging may lead to the elucidation of sex differences in the various symptoms of normal human aging. Geriatr Gerontol Int 2023;

Automated summary

This study investigated sex differences in patients with Werner syndrome (WS), a model of human aging. It found that male patients with WS were more likely to exhibit all cardinal signs compared to females. Female patients also had a lower frequency of a characteristic symptom of WS. The study highlights the importance of genetic testing for females with WS, even if they do not display typical symptoms. These findings suggest that there are sex differences in the phenotypes of hereditary progeroid syndromes and may contribute to understanding sex differences in normal human aging symptoms.