title: Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase.
abstract: BACKGROUND
  Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism. Over time, forms of thyroid dyshormonogenesis can result in goiter, which can lead to difficult management decisions as the pathologic changes can both mimic or lead to thyroid cancer.
  
  
  METHODS
  Herein we describe the cases of two brothers diagnosed with congenital hypothyroidism, with initial findings consistent with thyroid dyshormonogenesis. One brother eventually developed multinodular goiter with complex pathology on biopsy, resulting in thyroidectomy.
  
  
  RESULTS
  Whole exome sequencing revealed the brothers carry a novel frameshift mutation in thyroperoxidase; the mutation, while not previously described, was likely both deleterious and pathogenic. Conlcusions: These cases highlight the complex pathology that can occur within thyroid dyshormonogenesis, with similar appearance to possible thyroid cancer, leading to complex management decisions. They also highlight the role that a genetic diagnosis can play in interpreting the impact of dyshormonogenesis on nodular thyroid development, and the need for long-term follow-up in these patients.
authors.forename: David P
authors.identifier: http://orcid.org/0000-0001-5940-1544
authors.initials: DP
authors.lastname: Sparling
authors.forename: Kendra
authors.initials: K
authors.lastname: Fabian
authors.forename: Lara
authors.initials: L
authors.lastname: Harik
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.forename: Kwame
authors.initials: K
authors.lastname: Anyane-Yeboa
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Oberfield
authors.forename: Ilene
authors.initials: I
authors.lastname: Fennoy
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000235:genetics*; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D035781:Siblings; D013961:Thyroid Gland / Q000002:abnormalities* / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood*; D013965:Thyroidectomy
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; D013963:Thyroid Hormones; C056658:TPO protein, human; D007453:Iodide Peroxidase