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MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency

Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder presenting with abnormal eye development, which leads to glaucoma related blindness in 50% of individuals. Associated mutations affect the transcription factors pituitary homeobox 2 gene (PITX2) and forkhead box C1 gene (FOXC1). Three...

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Autores principales: Santini, Alberto Javier Grana, Canales Ramos, Nicolle M, Burgos Ortega, Nydia I, Torres, Wilnelia Medina, Castellano, Janet Colón, Gonzalez-Rodriguez, Loida Alejandra, Alvarado, Milliette, Ramirez, Margarita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208997/
http://dx.doi.org/10.1210/jendso/bvaa046.1346
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author Santini, Alberto Javier Grana
Canales Ramos, Nicolle M
Burgos Ortega, Nydia I
Torres, Wilnelia Medina
Castellano, Janet Colón
Gonzalez-Rodriguez, Loida Alejandra
Alvarado, Milliette
Ramirez, Margarita
author_facet Santini, Alberto Javier Grana
Canales Ramos, Nicolle M
Burgos Ortega, Nydia I
Torres, Wilnelia Medina
Castellano, Janet Colón
Gonzalez-Rodriguez, Loida Alejandra
Alvarado, Milliette
Ramirez, Margarita
author_sort Santini, Alberto Javier Grana
collection PubMed
description Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder presenting with abnormal eye development, which leads to glaucoma related blindness in 50% of individuals. Associated mutations affect the transcription factors pituitary homeobox 2 gene (PITX2) and forkhead box C1 gene (FOXC1). Three types of ARS have been described. PITX2 mutation causes ARS type I, which is associated to systemic malformations, including dental hypoplasia, redundant periumbilical skin, and growth hormone deficiency (GHD). This is the case of a 28-year-old male diagnosed with GHD during childhood. He was referred to a pediatric-endocrinologist at age 10 due to short stature. Evaluation showed a height-for-age curve below the 10th percentile. Physical examination with prominent forehead, decrease visual acuity, maxillary hypodontia, umbilical hernia, and delayed sexual maturity. Testing with reduced IGF-1 and delayed bone age. Clonidine GH stimulation confirmed the diagnosis of GDH. He was treated with somatropin, until linear growth decreased to ½ inch per year at age 16. GHD etiology was never established. At age 26, he developed progressive decrease in visual acuity. Ophthalmology evaluation disclosed polycoria, megalocornea and increase intraocular pressure, suggestive of ARS. Patient was referred to our endocrinology clinics for follow up of previous diagnosis of GHD. Based on clinical findings and history, sequence analysis and deletion/duplication testing of FOXC1, PAX6 and PITx2 were performed, with results positive for pathogenic variant PITX2, Exon 5, c.363_364delinsAA. Assessment of pituitary hormone axis was normal, and no persistent GHD found. No family members exhibited clinical signs of ARS. Axenfeld-Rieger syndrome is a rare genetic disease. PITX homeodomain transcription factors are critical for the development of the anterior segment of the eye and pituitary. Most mutations in PITX2 affect DNA binding and transactivation that leads to defects in cell proliferation and differentiation of the Rathke’s pouch. As a result, GHD may ensue. ARS patients are usually diagnosed during childhood after the development of vision abnormalities. The diagnosis remains primarily clinical upon identification of ocular abnormalities in the iris and cornea, and increased intraocular pressure. Systemic changes are rare findings in ARS, but may include face and tooth abnormalities and isolated growth hormone deficiency. Genetic diagnosis is based on identification of mutations. An adequate management of ARS requires a multidisciplinary approach. Although ophthalmologists usually diagnose this condition, some patients initially present with isolated growth impairment. This may lead to a delay in ophthalmologic evaluation and management. Thus, in patients with GHD of unknown etiology, it is important to have a high index of suspicion of ARS in order to decrease morbidity from vision loss.
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spelling pubmed-72089972020-05-13 MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency Santini, Alberto Javier Grana Canales Ramos, Nicolle M Burgos Ortega, Nydia I Torres, Wilnelia Medina Castellano, Janet Colón Gonzalez-Rodriguez, Loida Alejandra Alvarado, Milliette Ramirez, Margarita J Endocr Soc Neuroendocrinology and Pituitary Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder presenting with abnormal eye development, which leads to glaucoma related blindness in 50% of individuals. Associated mutations affect the transcription factors pituitary homeobox 2 gene (PITX2) and forkhead box C1 gene (FOXC1). Three types of ARS have been described. PITX2 mutation causes ARS type I, which is associated to systemic malformations, including dental hypoplasia, redundant periumbilical skin, and growth hormone deficiency (GHD). This is the case of a 28-year-old male diagnosed with GHD during childhood. He was referred to a pediatric-endocrinologist at age 10 due to short stature. Evaluation showed a height-for-age curve below the 10th percentile. Physical examination with prominent forehead, decrease visual acuity, maxillary hypodontia, umbilical hernia, and delayed sexual maturity. Testing with reduced IGF-1 and delayed bone age. Clonidine GH stimulation confirmed the diagnosis of GDH. He was treated with somatropin, until linear growth decreased to ½ inch per year at age 16. GHD etiology was never established. At age 26, he developed progressive decrease in visual acuity. Ophthalmology evaluation disclosed polycoria, megalocornea and increase intraocular pressure, suggestive of ARS. Patient was referred to our endocrinology clinics for follow up of previous diagnosis of GHD. Based on clinical findings and history, sequence analysis and deletion/duplication testing of FOXC1, PAX6 and PITx2 were performed, with results positive for pathogenic variant PITX2, Exon 5, c.363_364delinsAA. Assessment of pituitary hormone axis was normal, and no persistent GHD found. No family members exhibited clinical signs of ARS. Axenfeld-Rieger syndrome is a rare genetic disease. PITX homeodomain transcription factors are critical for the development of the anterior segment of the eye and pituitary. Most mutations in PITX2 affect DNA binding and transactivation that leads to defects in cell proliferation and differentiation of the Rathke’s pouch. As a result, GHD may ensue. ARS patients are usually diagnosed during childhood after the development of vision abnormalities. The diagnosis remains primarily clinical upon identification of ocular abnormalities in the iris and cornea, and increased intraocular pressure. Systemic changes are rare findings in ARS, but may include face and tooth abnormalities and isolated growth hormone deficiency. Genetic diagnosis is based on identification of mutations. An adequate management of ARS requires a multidisciplinary approach. Although ophthalmologists usually diagnose this condition, some patients initially present with isolated growth impairment. This may lead to a delay in ophthalmologic evaluation and management. Thus, in patients with GHD of unknown etiology, it is important to have a high index of suspicion of ARS in order to decrease morbidity from vision loss. Oxford University Press 2020-05-08 /pmc/articles/PMC7208997/ http://dx.doi.org/10.1210/jendso/bvaa046.1346 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Neuroendocrinology and Pituitary
Santini, Alberto Javier Grana
Canales Ramos, Nicolle M
Burgos Ortega, Nydia I
Torres, Wilnelia Medina
Castellano, Janet Colón
Gonzalez-Rodriguez, Loida Alejandra
Alvarado, Milliette
Ramirez, Margarita
MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency
title MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency
title_full MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency
title_fullStr MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency
title_full_unstemmed MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency
title_short MON-257 Axenfeld Rieger Syndrome: An Uncommon Cause of Growth Hormone Deficiency
title_sort mon-257 axenfeld rieger syndrome: an uncommon cause of growth hormone deficiency
topic Neuroendocrinology and Pituitary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208997/
http://dx.doi.org/10.1210/jendso/bvaa046.1346
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