Townes-Brocks Syndrome (TBS) is a rare hereditary disorder marked by congenital malformations, posing diagnostic challenges due to its phenotypic heterogeneity. Our nationwide cohort study, encompassing 20,666 individuals with hearing impairment in mainland China, explored the correlation between TBS and variations of SALL1 and DACT1. The study revealed five novel variations in SALL1, alongside two known ones. Additionally, through comprehensive clinical evaluation of a TBS family, we affirmed links between TBS and specific endocrine abnormalities. These findings deepened our understanding of TBS’s phenotypic-genotypic spectrum. Notably, molecular diagnostics in atypical TBS cases highlighted an underestimated prevalence. (By Dr Jing Cheng, https://jmg.bmj.com/content/early/2024/01/30/jmg-2023-109579 )

Pedigree, genetic data and clinical pictures of (a) typical and (b) atypical TBS families identified from CDGC cohort. Black arrows, probands. Grey blocks, suspected presentation of phenotypes. White arrow, membranous atresia of external acoustic meatus of the right ear of F1-III:1.