Concomitant mutations in the thyroglobulin and SLC26A4 genes leading to fetal goiter and congenital hypothyroidism in a patient with pendred syndrome

We described new forms of thyroglobulin gene (TG) mutation resulting in fetal goiter and congenital hypothyroidism in a pendred syndrome (PS) patient. Fetal hypothyroidism was diagnosed, based on ultrasonographic evidence of goiter alongside with fetal blood measurement of TSH (>100 mIU/L); levothyroxine intrauterine treatment was performed. At birth, ultrasound thyroid enlargement and primary hypothyroidism were confirmed. On Day 11, hearing screening using a combination of otoacoustic emissions and auditory brainstem response revealed profound bilateral sensorineural deafness. Genetic analysis revealed TG variants [c.727C>T,p.(Àrg243Trp) and c.67l8G>T,p.(Glu2240Stop) in heterozygosis. Mutation c.164+1delG,p.(Ser55Ilefs ∗11) in homozygosis of the SLC26A4 gene was also detected. The extension of the analysis to the patient’s parents revealed the presence of the heterozygous variant in the SLC26A4 gene [c.164+1delG] and in the TG gene [c.727C>T] in the father, and the heterozygous variant in the SLC26A4 gene [c.164+1delG] and in the TG gene [c.6718G>T] in the mother. This is the first report associating mutations in TG with a PS patient. The combination of genetic factors likely contributed to the patient’s clinical conditions, which included fetal goiter with CH and profound bilateral hearing loss, representing a rare instance of mutations linked to inherited thyroid disorders.