Laron Syndrome (Syndrome, Laron)

An autosomal recessive disorder characterized by short stature, defective GROWTH HORMONE RECEPTOR, and failure to generate INSULIN-LIKE GROWTH FACTOR I by GROWTH HORMONE. Laron syndrome is not a form of primary pituitary dwarfism (GROWTH HORMONE DEFICIENCY DWARFISM) but the result of mutation of the human GHR gene on chromosome 5.

Also Known As:

Syndrome, Laron; Growth Hormone Receptor Defect; Growth Hormone Receptor Deficiency; Laron Dwarfism; Laron Type Dwarfism I; Pituitary Dwarfism II; Primary GH Resistance; Primary Growth Hormone Resistance; Severe GH Insensitivity; Dwarfism II, Pituitary; Dwarfism IIs, Pituitary; Dwarfism, Laron; GH Resistance, Primary; Pituitary Dwarfism IIs; Growth Hormone Insensitivity Syndrome

Networked: 324 relevant articles (5 outcomes, 37 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Laron Syndrome (Syndrome, Laron)
2.	Neoplasms (Cancer)
3.	Type 2 Diabetes Mellitus (MODY)
4.	Duchenne Muscular Dystrophy (Muscular Dystrophy, Becker)
5.	Multiple Sclerosis

Experts

1.	Laron, Zvi: 41 articles (12/2021 - 01/2002)
2.	Laron, Z: 14 articles (08/2011 - 01/2000)
3.	Werner, Haim: 9 articles (12/2021 - 04/2017)
4.	Nagaraj, Karthik: 7 articles (12/2021 - 01/2018)
5.	Sarfstein, Rive: 7 articles (12/2021 - 01/2018)
6.	Kopchick, John J: 6 articles (01/2022 - 09/2004)
7.	Hwa, Vivian: 6 articles (01/2020 - 06/2007)
8.	Lapkina-Gendler, Lena: 5 articles (12/2021 - 01/2018)
9.	Yakar, Shoshana: 5 articles (12/2021 - 07/2013)
10.	Guevara-Aguirre, Jaime: 4 articles (01/2018 - 06/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Laron Syndrome:

1.	Insulin-Like Growth Factor I (IGF-1)IBA 12/01/1999 - "This study reveals that IGF-I treatment at a dose of 80 microg/kg twice daily is effective in patients with growth hormone insensitivity syndrome. " 01/01/2018 - "The only therapeutic treatment for Laron syndrome is recombinant insulin-like growth factor I (IGF-I), which has been shown to have various side effects. " 06/01/2012 - "Recombinant human IGF-I is an effective treatment of severe primary IGF deficiency, which is typical of patients with GH receptor defects (Laron syndrome). " 04/01/1995 - "A randomized, double blind, placebo-controlled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone receptor deficiency." 01/01/2023 - "Crucial role of IGF-1 was discovered inter alia through studies involving deficient patients with short stature, including Laron syndrome individuals. "
2.	Cyproheptadine (Periactin)FDA Link 01/01/2018 - "A novel treatment for height growth in patients with growth hormone insensitivity syndrome by cyproheptadine hydrochloride." 01/01/2018 - "Cyproheptadine HCl (CyproH) is an appetite-stimulating drug and while it was prescribed for a patient with growth hormone insensitivity syndrome (GHIS) for increasing appetite, his height growth was surprisingly increased. "
3.	Growth Hormone (Somatotropin)IBA 01/01/2016 - "A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective." 03/30/2023 - "Patients harbouring loss-of-function (LOF) STAT5B mutations exhibit postnatal growth failure due to lack of responsiveness to growth hormone as well as immune perturbation, a disorder called growth hormone insensitivity syndrome with immune dysregulation 1 (GHISID1). " 01/01/2022 - "Moreover, Sec23bki/ko mice exhibited severe growth restriction accompanied by growth hormone (GH) insensitivity, reminiscent of Laron syndrome. " 01/01/2020 - "Growth Hormone insensitivity (Laron syndrome): Report of a new family and review of Brazilian patients." 01/01/2014 - "Six patients (5 with Laron syndrome and 1 with type 1A growth hormone deficiency) were followed for a mean (±SD) of 8.2 ± 1.8 years. "
4.	Insulin (Novolin)FDA Link 01/10/2013 - "In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome. " 01/01/2023 - "Interestingly, inactivating mutations in the GH receptor in humans result in Laron syndrome (LS), a clinical entity characterized by increased serum levels of GH and decreased insulin growth factor-1 (IGF-1). " 06/24/2011 - "Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome." 09/01/2004 - "GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. " 01/01/1986 - "These are hypopituitarism, Laron dwarfism, leprechaunism, liver disease, primary hypothyroidism, extrapancreatic tumor hypoglycemia and severe insulin deficiency in experimental animals. "
5.	Peptides (Polypeptides)IBA 06/01/1993 - "With the availability of recombinant insulin-like growth factor-I (recIGF-I), it was possible to study whether this peptide could promote growth without noticeable side-effects in patients with growth hormone insensitivity syndrome (Laron syndrome). " 01/01/1997 - "Insulin-like growth factor-I (IGF-I) is a growth hormone-dependent peptide with growth and immunoregulatory properties, and in Laron syndrome growth hormone insensitivity induces impaired production of IGF-I. In the present study we have determined the neutrophil expression of IGF-I receptors (IGF-I-Rs), as well as the IGF-I-induced priming of neutrophil functional capacity, in two children with Laron syndrome treated with recombinant human IGF-I, and in age-matched controls. " 06/01/1994 - "We have selected GHRD (Laron syndrome) as the prototypic disorder of GHI, in part because such dramatic and rapid progress has been made in this clinical condition over the last 6 yr. These advances represent the fortunate convergence of: 1) the cloning of the GHR gene and the identification of deletions and mutations of this gene in GHRD; 2) the development of assay methods for measurement of the GHBP, IGF peptides, and binding proteins; 3) the discovery of a larger number of affected individuals than had been previously suspected, including the recognition and description of a large genetically homogeneous population of GHRD patients in Ecuador; and 4) the production of recombinant IGF-I for therapeutic trials in GHRD. " 01/01/2005 - "In classical GH insensitivity syndrome (GHIS), known as Laron syndrome, due to GH receptor (GHR) deficiency, serum IGF-I, IGFBP-3 and ALS are severely reduced with inability to produce these peptides during an IGF-I generation test. " 06/01/2005 - "The 20 genes with at least a 3-fold change, annotated with known phenotypic associations in the current gene databank (phenotype association, fold change) were aspartoacylase (Canavan disease, 9.96), growth hormone receptor (Laron dwarfism, idiopathic short stature, 8.25), lipoprotein lipase (familial chylomicronemia syndrome, lipoprotein lipase deficiency, 8.00), vitamin D (1,25- dihydroxyvitamin D3) receptor (involutional osteoporosis, vitamin D resistant rickets, 7.94), intercellular adhesion molecule 1 human rhinovirus receptor (cerebral malaria susceptibility, 7.16), peroxisomal membrane protein 3 35-kDa (Refsum disease, infantile form, Zellweger syndrome-3, 6.00), Bardet-Biedl syndrome 2 (Bardet-Biedl syndrome, 5.87), ribosomal protein S19 (Diamond Blackfan anemia, 5.85), apolipoprotein C-III (hypertriglyceridemia, 5.44), argininosuccinate lyase (argininosuccinicaciduria, 5.22), myosin VA (Griscelli syndrome-type pigmentary dilution with mental retardation, 4.92), lysozyme (renal amyloidosis, 4.17), SAM domain, SH3 domain and nuclear localisation signals 1 (Cherubism, 4.12 ), von Hippel-Lindau syndrome (hemangioblastoma, cerebellar, somatic, von Hippel-Lindau syndrome, 3.94), early-onset breast cancer 1 (BRCA1, papillary serous carcinoma of the peritoneum, 3.73), UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (inclusion body myopathy, autosomal recessive, sialuria, 3.53), apolipoprotein A-I (amyloidosis, 3 or more types, hypoalphalipoproteinemia, 3.29), midline 1 Opitz/BBB syndrome (Opitz G syndrome, type I, 3.28), ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide (familial hemiplegic migraine, 3.05). "
6.	Intercellular Signaling Peptides and Proteins (Growth Factors)IBA 07/01/2006 - "Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome." 07/01/2009 - "Treatment of growth hormone insensitivity syndrome with insulinlike growth factor-I appears to lead to an increase in dental maturation, particularly in younger patients. " 07/01/2009 - "This study evaluates the effects of 8 years of insulinlike growth factor-I therapy on tooth development in patients with growth hormone insensitivity syndrome. " 12/20/2007 - "BMP-2 is used in long bone and spinal surgery, PDGFbb for the treatment of periodontal defects and children with growth hormone receptor deficiency are treated with IGF-I.Aim of the present study was the comparative analysis of the effect of these growth factors released from a local drug delivery system on cells of the osteogenic lineage at differing differentiation stages.The" 01/01/2008 - "Laron syndrome is an autosomal recessive disorder of GH insensitivity that results in decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. "
7.	Somatotropin Receptors (Growth Hormone Receptor)IBA 12/01/2023 - "Growth hormone receptor knockout (GHR-KO) pigs have recently been developed, which serve as a large animal model of Laron syndrome (LS). " 09/19/2023 - "Although the majority of Growth Hormone insensitivity syndrome (GHIS) cases are classical, the spectrum of clinical phenotypes has expanded to include "atypical" GHIS subjects with milder phenotypes due to very rare heterozygous growth hormone receptor (GHR) mutations with dominant negative effects. " 07/20/2023 - "Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report." 01/01/2023 - "Mutations in growth hormone receptor (GHR) have been implicated in LS; hence, it is also known as growth hormone insensitivity syndrome (MIM-262500). " 03/01/2019 - "Laron syndrome related to homozygous growth hormone receptor c.784>C mutation in a patient with hypoplastic pulmonary arteries."
8.	Insulin-Like PeptidesIBA 01/01/2017 - "In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency). " 01/01/2023 - "Insulin-like growth factors and aging: lessons from Laron syndrome." 04/01/2018 - "Observations on the Laron syndrome originally offered the opportunity to explore the effect of insulin-like growth factor 1 (IGF-1) deficiency on human hair growth and differentiation. " 12/01/2015 - "To describe the characteristics of untreated and recombinant insulin-like growth factor 1 (IGF-1)- treated patients with the Laron syndrome (LS) as seen in our clinic over a period of over 50 years. " 01/01/2014 - "Further observations on the effects of long-term treatment with recombinant human insulin-like growth factor 1 in growth hormone insensitivity syndrome."
9.	somatotropin-binding protein (growth hormone-binding protein)IBA 01/01/1998 - "We have previously described two families (H and M) with GH binding protein-positive Laron Syndrome (LS), proposed to have one or more post GHR signaling defects. " 12/01/1997 - "A minority of patients with Laron syndrome have normal serum GH binding protein (GHBP), indicating that the defect is elsewhere than in the extracellular domain of the GH receptor. " 05/01/1997 - "Girls with Laron syndrome having positive growth hormone binding protein (GHBP) are less retarded in height than those lacking GHBP." 08/01/1995 - "Patients with idiopathic short stature have decreased serum levels of the GH receptor-related GH-binding protein (GHBP), and low GHBP levels are associated with complete GH insensitivity (Laron) syndrome. " 06/01/1994 - "In Laron syndrome, growth retardation is caused by GH resistance due to GH receptor (GH-R) defects, which are associated in most cases with absent or low serum concentrations of the GH-R-related GH-binding protein (GHBP). "
10.	Hormones (Hormone)IBA 04/01/2011 - "Only patients with an ascertained diagnosis of either Laron syndrome (LS), congenital IGHD, congenital multiple pituitary hormone deficiency (cMPHD) including GH or GHRHR defect were included in this study. " 01/01/2002 - "Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. " 08/01/1998 - "In two patients with growth hormone (GH) insensitivity syndrome (Laron syndrome), in whom the GH receptor is able to bind the hormone, the D152H mutation was identified, and lack of dimerization was proposed to explain GH resistance in these patients. " 01/01/1997 - "The difference in effectiveness between hGH and IGF-I in restoring muscle force may be due to either the more marked muscle underdevelopment in Laron syndrome patients than in patients with IGHD or a difference in action potential between the two hormones." 03/01/1993 - "Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism."

Therapies and Procedures

1.	Therapeutics 01/01/2018 - "The improved Laron syndrome models are important for better understanding the pathogenesis of the disease and developing corresponding therapeutics. " 02/01/2021 - "Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome." 01/01/2013 - "He had been diagnosed with Laron syndrome (LS) at 4 years old and rIGF-1 therapy was initiated. " 01/01/2006 - "IGF therapy has been successfully utilized in growth hormone insensitivity syndrome and GHD type 1B. " 01/01/2002 - "Most of the syndromes respond well to therapy with recombinant GH; exceptions are antibody-mediated resistance in GHD type IA (not all patients) and cases of Laron syndrome (GHR deficiency). "
2.	Subcutaneous Injections 10/01/1992 - "We studied the effects of 9 months of treatment with twice-daily subcutaneous injections of insulin-like growth factor I (IGF-I), 120 micrograms/kg per dose, in a 9.7-year-old child with growth hormone insensitivity syndrome, in whom short-term studies had suggested that IGF-I might promote linear growth. " 07/01/1995 - "Nine prepubertal children with Laron syndrome (6 males, 3 females) aged 0.5 to 14.6 years were treated by daily subcutaneous injections of IGF-I in doses of 150-200 micrograms/kg. All patients completed at least one year of treatment; six completed two years and five three years. " 12/01/1994 - "Eight children with Laron syndrome (5 males, 3 females) aged 3-14.5 years received daily subcutaneous injections of 150 micrograms/kg recombinant insulin-like growth factor-I (IGF-I) for 5 months. "
3.	Cell Transplantation 01/01/2018 - "For these reasons, this work reviews the application of both naked and microencapsulated Sertoli cells used in cell transplantation studies of several chronic or autoimmune diseases such as diabetes mellitus, Laron dwarfism, and Duchenne muscular dystrophy and in studies aimed at the prevention of skin allograft rejection."
4.	Glycemic Control 10/01/2008 - "Therapeutical human use of recombinant human IGF-1 (rhIGF-1) has been widely applied only in Laron syndrome, while being verified in many randomized controlled trials to improve glycemic control in type 1 and type 2 diabetes, and proposed in neurological disease such as amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer disease. "
5.	Injections 08/28/2018 - "Methods Repetitive blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after rhIGF-I injections in two male patients with Laron syndrome at times of dose adjustments. " 03/01/2013 - "Comparison of the growth velocity of 1 vs. 2 IGF-I injections per day in patients with Laron Syndrome (primary GH insensitivity) revealed similar effects." 02/01/1999 - "Eight children with growth hormone insensitivity syndrome (GHIS) have been treated with injections of recombinant human insulin-like growth factor I (rhIGF-I) for more than 5 years each. " 01/01/2022 - "The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). " 04/01/2003 - "SomatoKine, a recombinant fusion of insulin-like growth factor-1 and its binding protein, BP-3, is being developed by Insmed (formerly Celtrix Pharmaceuticals) for the potential treatment of growth hormone insensitivity syndrome (GHIS), and as a potential injectable insulin sensitizer for the management of type 1 and type 2 diabetes in patients who are less sensitive to insulin therapy. "