title: IGSF1 deficiency syndrome: A newly uncovered endocrinopathy.
abstract: A recently uncovered X-linked syndrome, caused by loss-of-function of IGSF1, is characterized by congenital central hypothyroidism and macroorchidism, variable prolactin deficiency, occasional growth hormone deficiency, delayed pubertal testosterone secretion and obesity. We propose to call this endocrinopathy "IGSF1 deficiency syndrome." Based on an estimated incidence of isolated congenital central hypothyroidism of 1:65,000, we predict that the incidence of IGSF1 deficiency related hypothyroidism is approximately 1:100,000. IGSF1 encodes a plasma membrane immunoglobulin superfamily glycoprotein that is highly expressed in pituitary and testis, but is of unknown function. The variable profile of pituitary dysfunction suggests that IGSF1 may play a role in pituitary paracrine regulation. The clinical significance of the syndrome, particularly the clinical consequences of untreated hypothyroidism, justifies screening family members of patients with IGSF1 mutations for carriership and to study potential carriers of IGSF1 mutations, including patients with idiopathic central hypothyroidism, combined GH and TSH deficiency, macroorchidism or delayed puberty.
authors.affiliation: Department of Pediatrics; Leiden University Medical Center; Leiden, The Netherlands ; Department of Endocrinology and Metabolic Disorders; Leiden University Medical Center; Leiden, The Netherlands.
authors.forename: Sjoerd D
authors.initials: SD
authors.lastname: Joustra
authors.affiliation: Department of Pediatric Endocrinology; Emma Children's Hospital; Academic Medical Center; University of Amsterdam; Amsterdam, The Netherlands.
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
authors.affiliation: Center for Human and Clinical Genetics; Leiden University Medical Center; Leiden, The Netherlands.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center for Human and Clinical Genetics; Leiden University Medical Center; Leiden, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
authors.affiliation: Department of Pharmacology and Therapeutics; McGill University; Montreal, QC Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bernard
authors.affiliation: Department of Endocrinology and Metabolic Disorders; Leiden University Medical Center; Leiden, The Netherlands.
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.affiliation: Department of Pediatrics; Leiden University Medical Center; Leiden, The Netherlands.
authors.forename: Wilma
authors.initials: W
authors.lastname: Oostdijk
authors.affiliation: Department of Pediatrics; Leiden University Medical Center; Leiden, The Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
keywords: IGSF1; central hypothyroidism; macroorchidism; obesity; prolactin