Genetics and management of congenital hypothyroidism

Luca Persani, Giuditta Rurale, Tiziana de Filippis, Elena Galazzi, Marina Muzza, Laura Fugazzola

Research output: Contribution to journalReview articlepeer-review


Several evidences support a relevant genetic origin for Congenital Hypothyroidism (CH), however familial forms are uncommon. CH can be due to morphogenetic or functional defects and several genes have been originally associated either with thyroid dysgenesis or dyshormonogenesis, with a highly variable expressivity and a frequently incomplete penetrance of the genetic defects. The phenotype-driven genetic analyses rarely yielded positive results in more than 10% of cases, thus raising doubts on the genetic origin of CH. However, more recent unsupervised approaches with systematic Next Generation Sequencing (NGS) analysis revealed the existence of hypomorphic alleles of these candidate genes whose combination can explain a significant portion of CH cases. The co-segregation studies of the hypothyroid phenotype with multiple gene variants in pedigrees confirmed the potential oligogenic origin of CH, which finally represents a suitable explanation for the frequent sporadic occurrence of this disease.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Issue number4
Publication statusPublished - Aug 1 2018


  • complication prevention
  • congenital hypothyroidism
  • goiter
  • next generation sequencing
  • systemic disease complications
  • thyroid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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