Growth Hormone Insensitivity
You are reading a NORD Rare Disease Report Abstract. NORD’s full collection of reports on over 1200 rare diseases is available to subscribers (click here for details). We are now also offering two full rare disease reports per day to visitors on our Web site.
NORD is very grateful to Arlan L. Rosenbloom, MD, Adjunct Distinguished Service Professor Emeritus, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, for assistance in the preparation of this report.
Synonyms of Growth Hormone Insensitivity
- GH insensitivity
- growth hormone resistance
- growth hormone unresponsiveness
- Laron syndrome
- GH inactivating antibodies
- GH postreceptor deficiencies
- GH receptor deficiency (GHRD)
Growth hormone insensitivity (GHI) is a group of extremely rare genetic disorders in which the body is unable to use the growth hormone that it produces. GHI can be caused by mutations in the growth hormone receptor (GHR) gene or mutations in genes involved in the action pathway within the cell after growth hormone binds to its receptor, preventing production of insulin-like growth factor (IGF-1), the substance responsible for the growth effects of growth hormone. Even more rarely, children with GH gene deletion who have been treated with recombinant GH develop antibodies that block GH binding to its receptor. Affected children fail to grow normally.
Children with GHRD who are treated with IGF-1 before puberty have improved growth, but, unlike children with GH deficiency given recombinant GH treatment, they do not have normal growth restored. Treatment for these conditions is only effective while the growing bones are still open, i.e. before the completion of adolescence. IGF-I insensitivity due to IGF-I receptor mutation mimics GHI, but results in less severe growth deficiency and is somewhat responsive to treatment with recombinant GH.
GHI is characterized by short stature and delayed bone age, as well as normal or high levels of circulating GH. Other common symptoms are delayed onset of puberty, prominent forehead, low blood sugar and obesity in adulthood. Except for an extremely rare form of GHI, where the gene for IGF-I is defective, brain development is normal, apparently because IGF-I can be made during fetal life without GH stimulation in the other conditions. Some, but definitely not all, patients with the less rare condition of IGF-I receptor deficiency may have mild intellectual impairment.
Laron and colleagues in Israel, first reported the condition in 1966, based on observations that began in 1958, and have continued to the present. The molecular basis for the syndrome he described, genetic mutation of the GHR in some of the Israeli patients was initially described in 1989, and since then over 40 different mutations of this protein have been identified by many investigators. The other genetic defects in the action pathway of GH after its binding to the GHR and associated with varying effects of IGF-I deficiency have been described in the past 15 years.
Organizations related to Growth Hormone Insensitivity
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
Copyright 1990, 1992, 1995, 2003, 2005, 2011, 2012
NORD's Rare Disease Information Database is copyrighted and may not be published without the written consent of NORD.