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Italian Journal of Pediatrics Oct 2017Mutations localized in the Growth Hormone Receptor (GHR) gene are often associated with the pathogenesis of Laron Syndrome, an autosomal recessive hereditary disorder... (Review)
Review
BACKGROUND
Mutations localized in the Growth Hormone Receptor (GHR) gene are often associated with the pathogenesis of Laron Syndrome, an autosomal recessive hereditary disorder characterized by severe growth retardation. Biochemically, patients present normal to high circulating GH levels, in presence of very low or undetectable IGF-I levels, which do not rise after rhGH treatment.
CASE PRESENTATION
We describe the case of a 3.8 years old girl with symmetrical short stature (-3.76 SDS), low IGF-1 and IGFBP-3, in presence of normal GH levels. Parents were not relatives and there was no family history of short stature. During the second day of birth, she developed severe hypoglycaemia that required glucose infusion. She presented frontal bossing and depressed nasal bridge. IGF-1 generation test showed no response, suggesting a GH resistance evidence. In the hypothesis of Laron Syndrome, we decided to perform a molecular analysis of Growth Hormone Receptor (GHR) gene. This analysis demonstrated that the patient was compound heterozygote for two missense mutations.
CONCLUSIONS
GHR gene mutations are a well demonstrated cause of GH insensitivity. In heterozygous patients, probably the normal stature may be achieved by a compensatory mechanism of GH secretion or signalling. On the contrary, in homozygous or compound heterozygous patients these compensatory mechanisms are inadequate, and short stature may be the consequence.
Topics: Child; Child, Preschool; Female; Genetic Predisposition to Disease; Heterozygote; Humans; Italy; Laron Syndrome; Mutation, Missense; Prognosis; Receptors, Somatotropin; Severity of Illness Index
PubMed: 29025428
DOI: 10.1186/s13052-017-0411-7 -
Cardiovascular Journal of AfricaLaron syndrome, also known as growth hormone insensitivity, is an autosomal recessive disorder characterised by short stature due to mutations or deletions in the growth...
Laron syndrome, also known as growth hormone insensitivity, is an autosomal recessive disorder characterised by short stature due to mutations or deletions in the growth hormone receptor (GHR), leading to congenital insulin-like growth factor 1 (IGF1) deficiency. Cardiac abnormalities, such as patent ductus arteriosus or peripheral vascular disease are rare in patients with Laron syndrome, but cardiac hypertrophy has been observed after IGF1 therapy. In this report, we present a 10-year-and-5-month-old girl with severe peripheral-type pulmonary artery hypoplasia and Laron syndrome related to homozygous GHR c.784>C mutation.
Topics: Carrier Proteins; Child; Female; Genetic Predisposition to Disease; Homozygote; Humans; Laron Syndrome; Mutation; Phenotype; Pulmonary Artery
PubMed: 30720842
DOI: 10.5830/CVJA-2019-002 -
The American Journal of the Medical... May 2017Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no...
BACKGROUND
Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency).
METHODS
A 21-year-old female Mexican patient with a genetic diagnosis of FA was referred to our research department for an evaluation of her short stature. Upon admission to our facility, her phenotype led to a suspicion of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed and a GH stimulation test was performed. In addition, we used a next-generation sequencing approach for a molecular evaluation of FA disease-causing mutations and genes involved in the GH-IGF signaling pathway.
RESULTS
Tests revealed low levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as well as a lack of response to GH stimulation. Sequencing confirmed a defect in the GH receptor signaling pathway.
CONCLUSIONS
To the best of our knowledge, this study is the first to suggest an association between FA and LS. We propose that IGF-1 administration might improve some FA complications and functions based upon IGF-1 beneficial actions observed in animal, cell and indirect clinical models: erythropoiesis modulation, immune function improvement and metabolic regulation.
Topics: Body Height; Fanconi Anemia; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Laron Syndrome; Mexico; Receptors, Somatotropin; Signal Transduction; Young Adult
PubMed: 28502327
DOI: 10.1016/j.amjms.2017.02.001 -
Metabolism: Clinical and Experimental Oct 1995Among 43 patients with Laron syndrome followed in our clinic, we were able to study the carbohydrate metabolism from infancy into adult age in 30 patients. During... (Review)
Review
Among 43 patients with Laron syndrome followed in our clinic, we were able to study the carbohydrate metabolism from infancy into adult age in 30 patients. During infancy, fasting blood glucose levels were in the hypoglycemic range (mean +/- SD, 3.5 +/- 1.2 mmol/L) and increased at the end of a delayed puberty to 4.6 +/- 0.6 mmol/L. Fasting plasma insulin was higher than expected for concomitant glucose levels, and several of the 20 patients who underwent an oral glucose tolerance test (OGTT) had glucose intolerance and relatively high insulin levels. In adult patients, insulinopenia developed and one 38-year-old patient developed non-insulin-dependent diabetes mellitus (NIDDM) with subsequent need for insulin therapy. Continuous insulin-like growth factor-I (IGF-I) treatment of a pubertal patient with glucose intolerance and hyperinsulinemia normalized both responses. In conclusion, long-term IGF-I deficiency leads to insulin resistance, which is reversed by exogenous IGF-I administration.
Topics: Blood Glucose; Carbohydrate Metabolism; Growth Disorders; Growth Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Obesity
PubMed: 7476303
DOI: 10.1016/0026-0495(95)90231-7 -
Frontiers in Physiology 2022Growth hormone (GH) is a peptide hormone that can signal directly through its receptor or indirectly through insulin-like growth factor 1 (IGF-1) stimulation. GH draws... (Review)
Review
Growth hormone (GH) is a peptide hormone that can signal directly through its receptor or indirectly through insulin-like growth factor 1 (IGF-1) stimulation. GH draws its name from its anabolic effects on muscle and bone but also has distinct metabolic effects in multiple tissues. In addition to its metabolic and musculoskeletal effects, GH is closely associated with aging, with levels declining as individuals age but GH action negatively correlating with lifespan. GH's effects have been studied in human conditions of GH alteration, such as acromegaly and Laron syndrome, and GH therapies have been suggested to combat aging-related musculoskeletal diseases, in part, because of the decline in GH levels with advanced age. While clinical data are inconclusive, animal models have been indispensable in understanding the underlying molecular mechanisms of GH action. This review will provide a brief overview of the musculoskeletal effects of GH, focusing on clinical and animal models.
PubMed: 35665221
DOI: 10.3389/fphys.2022.867921 -
Growth Hormone & IGF Research :... Apr 2012Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth. (Comparative Study)
Comparative Study Review
Head circumference in untreated and IGF-I treated patients with Laron syndrome: comparison with untreated and hGH-treated children with isolated growth hormone deficiency.
BACKGROUND
Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth.
OBJECTIVE
To determine the effects of long IGF-I deficiency and treatment on HC in patients with Laron syndrome (LS).
PATIENTS
20 untreated adult LS patients, aged 48.4±11.2 years and 13 LS patients treated between ages of 5.6±4 to 11.3±3 years were studied. 15 patients with congenital IGHD treated between age 6.1±4 and 13±4 by hGH served as controls.
METHODS
HC was expressed as standard deviation (SD) and Ht as SDS. HC was measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a Harpenden Stadiometer.
CONCLUSIONS
The mean HC deficit of the adult untreated LS males was -2.9±0.6 SD compared to a Ht deficit of -7.0±1.7 SDS. The HC of the LS adult females was -3.6±1 SD compared to a Ht SDS of -6.9±1.5 (p<0.001). IGF-I treatment (150-200 μg/kg once daily) increased the HC from -3.3±0.9 (m±SD) to normal values (0.87±1.8 SD) (p<0.001) in 11/13 children. The Ht SDS deficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the HC from -2.0±1.8 to 0.3±1.2 SD and the Ht SDS from -4.8±1.6 to 1.6±1.0.
Topics: Adolescent; Adult; Brain; Case-Control Studies; Cephalometry; Child; Child, Preschool; Dwarfism, Pituitary; Female; Growth Hormone; Head; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Male; Middle Aged
PubMed: 22414926
DOI: 10.1016/j.ghir.2012.02.005 -
Archives of Disease in Childhood Jun 1993Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14...
Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls completed their growth between the age of 16-19 years to a final mean (SD) height of 119 (8.5) cm whereas the boys continued growing beyond the age of 20 years, achieving a final height of 124 (8.5) cm. At all ages the upper to lower body segment ratio was more than 2 SD above the normal mean. These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency. They should also be useful in the follow up of children with Laron syndrome treated with biosynthetic recombinant IGF-I.
Topics: Age Factors; Body Height; Female; Follow-Up Studies; Growth Disorders; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Male; Syndrome
PubMed: 8333769
DOI: 10.1136/adc.68.6.768 -
Archives of Disease in Childhood Mar 1993
Topics: Child; Chromosome Deletion; Dwarfism; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Receptors, Somatotropin; Syndrome
PubMed: 8466235
DOI: 10.1136/adc.68.3.345 -
AJNR. American Journal of Neuroradiology Apr 2002Patients with Laron syndrome have an inborn growth hormone resistance. We investigated abnormalities in the upper airways and cervical spine in patients with Laron...
BACKGROUND AND PURPOSE
Patients with Laron syndrome have an inborn growth hormone resistance. We investigated abnormalities in the upper airways and cervical spine in patients with Laron syndrome.
METHODS
We prospectively examined 11 patients (one child aged 9 years and 10 adults aged 36-68 years), 10 of whom underwent MR imaging of the spine or head; nine, radiography of the cervical spine; and four, CT of C1-C2. The width of the spinal canal was evaluated visually and quantitatively and compared with reference values. The smallest diameter of the oropharynx and the thickness of the palate were measured and compared with reference values. Nine age-matched female patients referred for MR imaging for unrelated reasons served as control subjects.
RESULTS
Cervical spinal stenosis was present in seven of the adult patients, within a confidence interval of 95%. Anomaly of the dens compatible with os odontoideum was present in three patients, causing focal myelomalacia in two. The atlanto-odontoid joint showed osteoarthritic changes in six of the adult patients. The mediolateral diameter of the oropharynx was significantly smaller in the patients with Laron syndrome than in the control subjects (P <.005). There was no difference in the thickness of the soft palate.
CONCLUSION
Patients with Laron syndrome develop significant narrowing of the cervical spinal canal and early degenerative changes of the atlanto-odontoid joint. Laron syndrome is associated with os odontoideum causing myelomalacia. The dimensions of the oropharynx are small. Patients may be prone to neurologic morbidity and sleep disturbances. Routine MR imaging of the cervical spine is recommended in these patients.
Topics: Adult; Aged; Atlanto-Axial Joint; Cervical Vertebrae; Child; Dwarfism; Female; Humans; Insulin-Like Growth Factor I; Magnetic Resonance Imaging; Male; Middle Aged; Odontoid Process; Oropharynx; Osteoarthritis; Prospective Studies; Spinal Canal; Spinal Stenosis; Tomography, X-Ray Computed
PubMed: 11950656
DOI: No ID Found -
Recent Progress in Hormone Research 1993
Review
Topics: Amino Acid Sequence; Dwarfism; Genetic Linkage; Growth Hormone; Humans; Molecular Sequence Data; Mutation; Phenotype; Receptors, Somatotropin; Syndrome
PubMed: 8441847
DOI: 10.1016/b978-0-12-571148-7.50010-5