title: Genetics of normal and abnormal thyroid development in humans.
abstract: The most frequent cause of congenital hypothyroidism is thyroid dysgenesis. Thyroid dysgenesis summarizes a spectrum of developmental abnormalities of the embryonic thyroid ranging from complete absence of the thyroid gland (athyreosis), to a normally located but too small thyroid (hypoplasia), or an abnormally located thyroid gland (ectopy). Although considered a sporadic disease, distinct genetic forms of isolated or syndromic thyroid dysgenesis have been described in recent years. However, genetics of thyroid dysgenesis (TD) are mostly not following simple Mendelian patterns, and beside monogenic, multigenic and epigenetic mechanisms need to be considered. The review will highlight the molecular mechanisms of thyroid organogenesis, clinical and genetic features of the different monogenetic forms of thyroid dysgenesis, the aspects relevant for diagnosis and counseling of affected families and current research strategies to get more insight into the non-Medelian mechanisms of normal and abnormal thyroid development.
authors.affiliation: Division of Paediatric Endocrinology and Diabetology, University Children's Hospital Basel UKBB, Spitalstrasse 33, CH-4031 Basel, Switzerland; Department of Biomedicine, University Basel, Spitalstrasse 33, CH-4031 Basel, Switzerland. Electronic address: gabor.szinnai@unibas.ch.
authors.forename: Gabor
authors.initials: G
authors.lastname: Szinnai
mesh_terms: D000818:Animals; D003409:Congenital Hypothyroidism / Q000209:etiology / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005865:Gestational Age; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology; D007231:Infant, Newborn; D008822:Mice, Transgenic; D015997:Neonatal Screening; D011989:Receptors, Thyrotropin / Q000235:genetics; D013959:Thyroid Diseases / Q000150:complications; D050033:Thyroid Dysgenesis / Q000235:genetics; D013961:Thyroid Gland / Q000002:abnormalities / Q000196:embryology*
chemical_list: D011989:Receptors, Thyrotropin
keywords: Mendelian inheritance; congenital hypothyroidism; endoderm; epigenetics; neonatal screening; thyroid development; thyroid dysgenesis; thyroxine