HES1 and cyclic hematopoiesis: Although this explains only a small proportion of cases, it is higher than that documented in 90 Brazilian CH-TD patients, where PAX8, NKX2-5, TSHR, and HES1 (MIM * 139605) did not reveal any pathogenic or VUS change [31,32], and seems quite similar to the rate obtained in Japanese CH patients (2.0%, N = 2/102), at least 50% of whom carried a confirmed TD phenotype [16].