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Genetics of congenital hypothyroidism
  1. S M Park1,
  2. V K K Chatterjee2
  1. 1Department of Clinical Genetics, Addenbrooke’s Hospital, Cambridge, UK
  2. 2Department of Medicine, University of Cambridge, Addenbrooke’s Hospital
  1. Correspondence to:
 Dr S M Park
 Department of Clinical Genetics, Box 134, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK;


Congenital hypothyroidism is the most common neonatal metabolic disorder and results in severe neurodevelopmental impairment and infertility if untreated. Congenital hypothyroidism is usually sporadic but up to 2% of thyroid dysgenesis is familial, and congenital hypothyroidism caused by organification defects is often recessively inherited. The candidate genes associated with this genetically heterogeneous disorder form two main groups: those causing thyroid gland dysgenesis and those causing dyshormonogenesis. Genes associated with thyroid gland dysgenesis include the TSH receptor in non-syndromic congenital hypothyroidism, and Gsα and the thyroid transcription factors (TTF-1, TTF-2, and Pax-8), associated with different complex syndromes that include congenital hypothyroidism. Among those causing dyshormonogenesis, the thyroid peroxidase and thyroglobulin genes were initially described, and more recently PDS (Pendred syndrome), NIS (sodium iodide symporter), and THOX2 (thyroid oxidase 2) gene defects. There is also early evidence for a third group of congenital hypothyroid conditions associated with iodothyronine transporter defects associated with severe neurological sequelae. This review focuses on the genetic aspects of primary congenital hypothyroidism.

  • ERSD, endoplasmic reticulum storage disease
  • NIS, sodium iodide symporter
  • PHP, pseudohypoparathyroidism
  • PPHP, pseudopseudo‐hypoparathyroidism
  • PTH, parathyroid hormone
  • TPO, thyroid peroxidase
  • TRH, thyrotropin releasing hormone
  • TSH, thyroid stimulating hormone (thyrotropin)
  • congenital hypothyroidism
  • candidate gene

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  • Competing interests: none declared

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