The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth

Our objective was to further expand the spectrum of clinical characteristics of the IGSF1 deficiency syndrome in affected males. These characteristic include almost universal congenital central hypothyroidism (CeH) with disharmonious pubertal development (normally timed testicular growth, but delaye...

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Autores principales:	Steven Ghanny, Aliza Zidell, Helio Pedro, Sjoerd D. Joustra, Monique Losekoot, Jan M. Wit, Javier Aisenberg
Formato:	article
Lenguaje:	EN
Publicado:	Galenos Yayincilik 2021
Materias:	igsf1 deficiency hypothyroidism macroorchidism obesity prolactin Pediatrics RJ1-570 Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/8b1e0cff09ee45c983376646b4e3544f
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spelling	oai:doaj.org-article:8b1e0cff09ee45c983376646b4e3544f2021-11-26T06:10:17ZThe IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth1308-57271308-573510.4274/jcrpe.galenos.2020.2020.0125https://doaj.org/article/8b1e0cff09ee45c983376646b4e3544f2021-12-01T00:00:00Z http://www.jcrpe.org/archives/archive-detail/article-preview/the-gsf1-deficiency-syndrome-may-present-with-norm/41613 https://doaj.org/toc/1308-5727https://doaj.org/toc/1308-5735Our objective was to further expand the spectrum of clinical characteristics of the IGSF1 deficiency syndrome in affected males. These characteristic include almost universal congenital central hypothyroidism (CeH) with disharmonious pubertal development (normally timed testicular growth, but delayed rise of serum testosterone), macroorchidism, increased body mass index (BMI), and decreased attentional control. In addition, a subset of patients show prolactin deficiency, transient partial growth hormone deficiency in childhood and increased growth hormone secretion in adulthood. We present a family in which the proband was diagnosed with CeH and low serum prolactin. Severe weight gain started at two years old, with a BMI of 42.3 at 13.9 years. Testicular enlargement (5-6 mL, 3.8-4.3 standard deviation score) started aged three years. A pathogenic variant was found in the IGSF1 gene: c.3411_3412del, p.(Tyr1137*). His brother was referred for short stature at age 13 years and was diagnosed with CeH, normal serum prolactin and IGF-1, and disharmonious puberty. In four male relatives (the proband’s brother and three cousins) with the variant (one adult), free thyroxine (fT4) was below the lower limit of the reference range in two, and just above this limit in the other two. Three were overweight or obese, adolescents had disharmonious pubertal development and the adult had profound macroorchidism. In conclusion, male hemizygous carriers of a pathogenic IGSF1 variant can present with fT4 concentration above the lower limit of the reference range while severe early onset obesity or premature testicular growth are part of the phenotypic spectrum.Steven GhannyAliza ZidellHelio PedroSjoerd D. JoustraMonique LosekootJan M. WitJavier AisenbergGalenos Yayincilikarticleigsf1 deficiencyhypothyroidismmacroorchidismobesityprolactinPediatricsRJ1-570Diseases of the endocrine glands. Clinical endocrinologyRC648-665ENJCRPE, Vol 13, Iss 4, Pp 461-467 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	igsf1 deficiency hypothyroidism macroorchidism obesity prolactin Pediatrics RJ1-570 Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	igsf1 deficiency hypothyroidism macroorchidism obesity prolactin Pediatrics RJ1-570 Diseases of the endocrine glands. Clinical endocrinology RC648-665 Steven Ghanny Aliza Zidell Helio Pedro Sjoerd D. Joustra Monique Losekoot Jan M. Wit Javier Aisenberg The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth
description	Our objective was to further expand the spectrum of clinical characteristics of the IGSF1 deficiency syndrome in affected males. These characteristic include almost universal congenital central hypothyroidism (CeH) with disharmonious pubertal development (normally timed testicular growth, but delayed rise of serum testosterone), macroorchidism, increased body mass index (BMI), and decreased attentional control. In addition, a subset of patients show prolactin deficiency, transient partial growth hormone deficiency in childhood and increased growth hormone secretion in adulthood. We present a family in which the proband was diagnosed with CeH and low serum prolactin. Severe weight gain started at two years old, with a BMI of 42.3 at 13.9 years. Testicular enlargement (5-6 mL, 3.8-4.3 standard deviation score) started aged three years. A pathogenic variant was found in the IGSF1 gene: c.3411_3412del, p.(Tyr1137*). His brother was referred for short stature at age 13 years and was diagnosed with CeH, normal serum prolactin and IGF-1, and disharmonious puberty. In four male relatives (the proband’s brother and three cousins) with the variant (one adult), free thyroxine (fT4) was below the lower limit of the reference range in two, and just above this limit in the other two. Three were overweight or obese, adolescents had disharmonious pubertal development and the adult had profound macroorchidism. In conclusion, male hemizygous carriers of a pathogenic IGSF1 variant can present with fT4 concentration above the lower limit of the reference range while severe early onset obesity or premature testicular growth are part of the phenotypic spectrum.
format	article
author	Steven Ghanny Aliza Zidell Helio Pedro Sjoerd D. Joustra Monique Losekoot Jan M. Wit Javier Aisenberg
author_facet	Steven Ghanny Aliza Zidell Helio Pedro Sjoerd D. Joustra Monique Losekoot Jan M. Wit Javier Aisenberg
author_sort	Steven Ghanny
title	The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth
title_short	The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth
title_full	The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth
title_fullStr	The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth
title_full_unstemmed	The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth
title_sort	igsf1 deficiency syndrome may present with normal free t4 levels, severe obesity, or premature testicular growth
publisher	Galenos Yayincilik
publishDate	2021
url	https://doaj.org/article/8b1e0cff09ee45c983376646b4e3544f
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The IGSF1 Deficiency Syndrome May Present with Normal Free T4 Levels, Severe Obesity, or Premature Testicular Growth

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