||Heiko Krude, AG.|
||Molecular genetic basis of thyroid dysgenesis|
||An. pediatr. (2003. Ed. impr.);70(supl.esp.1):1-3, mayo 2009. ilus.
||As in other organ malformations, e.g. of the heart and the kidney, congenital defects of the thyroid gland occur mostly sporadic (1 in 3500 newborns). In the few familial cases of organ malformations, genetic defects in transcription factor genes were identified which are inherited mainly dominantly with a variable penetrance. For thyroid malformations, which manifest as the complete absence of the gland (athyrosis) or thyroid ectopy and thyroid hypoplasia, mutations in the transcription factor genes PAX8, NKX2.1 (TITF1), FOXE1 and NKX2.5 were described so far 1 . Together these mutations, although investigated in hundreds of patients, were detected in less than 50 of affected children. Therefore, the molecular pathogenesis of organ malformations, including the thyroid, are still unknown. To better understand the pathogenesis of organ malformations, further genes involved in early organ development need to be identified and to be tested as candidate genes. In addition new mechanisms need to be elucidated as potentially involved in the nonclassical defects leading to sporadic occurrence. Due to the sporadic occurrence classic mendelian inheritance is an unlikely cause in these conditions. Alternative molecular mechanisms like high rates of spontaneously occurring de-novo somatic mutations and epigenetic defects are possibly involved. Related with this likely non-mendelian inheritance, the variability of the manifestation of organ malformation, even in those cases with already proven mutations within the same transcription factor genes suggest epigenetic modification of the manifestation of organ malformations (fi g. 1) (AU)|