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Reviews in Endocrine & Metabolic... Mar 2021Laron Syndrome (LS) [OMIm#262500], or primary GH insensitivity, was first described in 1966 in consanguineous Jewish families from Yemen. LS is characterized by a... (Review)
Review
Laron Syndrome (LS) [OMIm#262500], or primary GH insensitivity, was first described in 1966 in consanguineous Jewish families from Yemen. LS is characterized by a typical phenotype that includes dwarfism, obesity and hypogenitalism. The disease is caused by deletions or mutations of the GH-receptor gene, causing high serum GH and low IGF-I serum levels. We studied 75 patients from childhood to adult age. After early hypoglycemia due to the progressive obesity, patients tend to develop glucose intolerance and diabetes. The treatment is by recombinant IGF-I, which improves the height and restores some of the metabolic parameters. An unexpected finding was that patients homozygous for GH-R defects are protected from malignancy lifelong, not so heterozygotes or double heterozygote subjects. We estimate that there are at least 500 patients worldwide, unfortunately only few treated.
Topics: Adult; Child; Growth Hormone; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Mutation; Neoplasms; Obesity; Receptors, Somatotropin
PubMed: 32964395
DOI: 10.1007/s11154-020-09595-0 -
Cells Nov 2020Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor () gene and is typically associated with dwarfism and... (Review)
Review
Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor () gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies. Epidemiological analyses have shown that LS patients do not develop cancer, whereas heterozygous family members have a cancer prevalence similar to the general population. To identify genes and signaling pathways differentially represented in LS that may help delineate a biochemical and molecular basis for cancer protection, we have recently conducted a genome-wide profiling of LS patients. Studies were based on our collection of Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene expression in several pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in the control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by '' genomic data from LS patients, we were able to generate clinically-relevant information in oncology and, potentially, related disciplines.
Topics: Animals; Biomedical Research; Humans; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Laron Syndrome; Neoplasms; Risk Factors
PubMed: 33182502
DOI: 10.3390/cells9112446 -
Journal of Postgraduate Medicine 2020[This corrects the article DOI: 10.4103/0022-3859.138816].
[This corrects the article DOI: 10.4103/0022-3859.138816].
PubMed: 32270785
DOI: 10.4103/0022-3859.169761 -
Frontiers in Endocrinology 2023The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this... (Review)
Review
The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this network in different animal species, including flies, nematodes and mouse, was consistently associated with an extended lifespan. Epidemiological analyses have shown that patients with Laron syndrome (LS), the best-characterized disease under the umbrella of the congenital IGF1 deficiencies, seem to be protected from cancer. While aging and cancer, as a rule, are considered diametrically opposite processes, modern lines of evidence reinforce the notion that aging and cancer might, as a matter of fact, be regarded as divergent manifestations of identical biochemical and cellular underlying processes. While the effect of individual mutations on lifespan and health span is very difficult to assess, genome-wide screenings identified a number of differentially represented aging- and longevity-associated genes in patients with LS. The present review summarizes recent data that emerged from comprehensive analyses of LS patients and portrays a number of previously unrecognized targets for GH-IGF1 action. Our article sheds light on complex aging and longevity processes, with a particular emphasis on the role of the GH-IGF1 network in these mechanisms.
Topics: Humans; Mice; Animals; Laron Syndrome; Aging; Longevity; Growth Hormone; Human Growth Hormone; Neoplasms
PubMed: 37941907
DOI: 10.3389/fendo.2023.1291812 -
Journal of Postgraduate Medicine 2014
Topics: Child; Child, Preschool; Developmental Disabilities; Growth Hormone; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Male
PubMed: 25121377
DOI: 10.4103/0022-3859.138816 -
Cells Jun 2019Laron syndrome (LS), or primary growth hormone resistance, is a prototypical congenital insulin-like growth factor 1 (IGF1) deficiency. The recent epidemiological... (Review)
Review
Laron syndrome (LS), or primary growth hormone resistance, is a prototypical congenital insulin-like growth factor 1 (IGF1) deficiency. The recent epidemiological finding that LS patients do not develop cancer is of major scientific and clinical relevance. Epidemiological data suggest that congenital IGF1 deficiency confers protection against the development of malignancies. This 'experiment of nature' reflects the critical role of IGF1 in tumor biology. The present review article provides an overview of recently conducted genome-wide profiling analyses aimed at identifying mechanisms and signaling pathways that are directly responsible for the link between life-time low IGF1 levels and protection from tumor development. The review underscores the concept that 'data mining' an orphan disease might translate into new developments in oncology.
Topics: Genome-Wide Association Study; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Neoplasms; Oncogenes; Signal Transduction
PubMed: 31208077
DOI: 10.3390/cells8060596 -
Gene Therapy Jun 2022
Topics: Genetic Therapy; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Mutation
PubMed: 35283485
DOI: 10.1038/s41434-022-00329-2 -
Journal of the ASEAN Federation of... 2023Primary growth hormone (GH) resistance or growth hormone insensitivity syndrome, also called Laron syndrome, is a hereditary disease caused by mutations in the GH...
Primary growth hormone (GH) resistance or growth hormone insensitivity syndrome, also called Laron syndrome, is a hereditary disease caused by mutations in the GH receptor or in the post-receptor signaling pathway. This disorder is characterized by postnatal growth failure resembling GH deficiency. Differentiating the two conditions is necessary. We present the cases of two siblings, a 16-year-old female and a 9-year-old male, born from a consanguineous union. Both had normal birth weights with subsequent severe short stature and delayed teeth eruption, with no features suggestive of any systemic illness. Serum insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) were both low. Suspecting GH deficiency, provocative testing with clonidine was done revealing peak growth hormone >40 ng/mL in both patients. In view of low IGF1 and IGFBP3 and high GH on stimulation, IGF1 generation test was done for both siblings, with values supporting the diagnosis of GH insensitivity or Laron syndrome.
Topics: Male; Female; Humans; Adolescent; Child; Laron Syndrome; Siblings; Growth Hormone; Human Growth Hormone; Receptors, Somatotropin
PubMed: 38045665
DOI: 10.15605/jafes.038.02.22 -
Reviews in Endocrine & Metabolic... Mar 2021The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their... (Review)
Review
The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world's largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.
Topics: Ecuador; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Laron Syndrome; Phenotype; Receptors, Somatotropin
PubMed: 33047268
DOI: 10.1007/s11154-020-09602-4 -
Hormone Research in Paediatrics 2022The aim of the study was to describe focal epilepsy in patients with Laron syndrome (LS).
OBJECTIVE
The aim of the study was to describe focal epilepsy in patients with Laron syndrome (LS).
METHODS
Data were retrieved from medical records of a single-center cohort of 75 patients with LS.
RESULTS
We describe for the first time 4 patients with concomitant focal epilepsy and LS. Two of them experienced episodes of status epilepticus. Electroencephalogram examination in all 4 patients showed interictal epileptiform discharges in the temporal regions. Three achieved long-term seizure freedom on antiseizure medications.
CONCLUSION
Patients with LS may be at risk of developing focal epilepsy, which seems to be unrelated to hypoglycemic episodes in childhood.
Topics: Electroencephalography; Epilepsies, Partial; Humans; Laron Syndrome; Retrospective Studies; Seizures
PubMed: 35358968
DOI: 10.1159/000524350