Genetic evaluation of a group of patients with transient congenital hypothyroidism by targeted exome sequencing

Transient congenital hypothyroidism (TCH) is characterized by congenital hypothyroidism (CH) which spontaneously resolves in the first years of life. While most cases are sporadic, several studies from worldwide showed variants in DUOX2, DUOXA2, TSHR genes in the etiology of TCH. The aim of our study is to evaluate the genetic etiology of TCH.

A total of 54 patients from 50 families with TCH were included the study. The age at diagnosis, age at time of drug discontinuation, gender, consanguinity, the presence of additional examination findings, venous fT4 and TSH levels at the time of diagnosis, at time of drug discontinuation and at the last visit, the follow-up data and genetic characteristics were obtained from records.

A total of 54 patients from 50 families [59.3 % male (n=32) and 40.7 % female (n=22)] with TCH were included in the study. Pathogenic variants were detected in 15 out of 54 patients. 10 different DUOX2 variants (c.1060C>T, c.1547G>A, c.2597T>G, c.3314T>C, c.3382C>A, c.3509A>C, c.3790A>G, c.4445C>T, c.28del, c.533G>T) were identified in 11 patients (2 homozygous, 3 compound heterozygous, and 6 heterozygous).

Our findings suggest that DUOX2 variants are the main genetic cause of TCH. We reported novel variants in the DUOX2 and TSHR genes that expand their mutational spectrum. These findings support the need for incorporating molecular analysis into the diagnostic evaluation of TCH, not only to improve our knowledge of its genetic underly, but also to provide valuable insights for long-term follow-up, family counseling, and personalized management strategies.