Thyroid hemiagenesis (THA) is a congenital lack of one thyroid lobe, with an incidence of 0.05–0.5% in population. Although THA was previously considered a benign thyroid maldevelopment, latest data suggest that it might be associated with an increased incidence of compensatory hypertrophy of a single thyroid lobe, nodular goiter, and possibly autoimmune thyroid diseases.
Familial occurrence of thyroid developmental anomalies (TDA), coincidence of TDA and several genetic syndromes together with an observation that THA is strain-dependent in rats suggest a genetic background. The first genes suspected to be involved in thyroid embryogenesis were thyroid transcription factors. However, mutations in these genes turned out to be causative only in a few patients with severe syndromic forms of TDA, mainly thyroid agenesis or ectopy, while etiopathogenesis of majority THA isolated forms remains unknown.
To date, in THA patients only a heterozygous mutation in PAX8 gene was documented as genetic cause. Recently, our group has demonstrated that proteasome genes mutations may be associated with THA phenotype. Furthermore several uncertain changes, but no deleterious mutations in HOXB3, HOXD3, and PITX2, were detected. In another patient with THA, a microduplication of chromosome region 22q11.2 encompassing TBX1 gene was found. The aim of the study was to identify novel genetic factors potentially responsible for thyroid maldevelopment by extensive genetic analysis of two patients with a familial form of THA.