Growth Hormone insensitivity (Laron syndrome): Report of a new family and review of Brazilian patients

Abstract

Laron's syndrome (LS) is a rare genetic disorder characterized by insensitivity to growth hormone (GH). Up to the present time, over 70 mutations of GH receptor (GHR) gene have been identified leading to GH/insulin-like growth factor type 1 (IGF1) signaling pathway defect. The number of LS patients worldwide is unknown, as many are probably undiagnosed. We report two sibs from a consanguineous family from Minas Gerais, southeastern Brazil. The parents have three children. The older, a 4-years-old girl was 80.2 cm tall (-5.7 SDS height/age), and the youngest sister, aged 3 years, was 73.2 cm tall (-5.82 SDS height/age). Their clinical and biochemical features are typical of LS patients, such as high serum level of GH and low IGF1 concentrations. A homozygous c.1A>T nucleotide substitution in GHR exon 2 in the probands' samples was identified. Their parents and healthy sister are heterozygous for the same variant that abolishes the translation initiation codon of GHR. This mutation has not been reported in Brazilian patients and was previously associated with an LS phenotype in a single 29-year-old Spanish man. In addition to this case report, we summarize the main characteristics and molecular data of the 21 LS Brazilian patients who have been published to date.Patients with LS have characteristic biochemical features, such as high (or normal) serum level of GH and low IGF1 concentration (Laron, 2004;Laron et al., 2012). Clinically it is characterized by dwarfism, obesity, small genitalia in the boys, and severe hypoglycemia. Patients present a typical head configuration, a small face and a protruding forehead, resulting in a saddle nose. Their voices are highpitched and they are sparse haired. Phenotypically they re-

Role of the GH-IGF1 axis on the hypothalamus–pituitary–testicular axis function: lessons from Laron syndrome

“…1 ). These patients are concentrated in the Mediterranean area, southern Ecuador, and South America, with a similar gender distribution ( 10 ). The main features of the included studies are summarized in Table 1 .…”

“…Therefore, the purpose of this systematic review is to analyze the evidence collected over the years on this topic in patients with Laron syndrome, to highlight the effects of low IGF1 on the human HPT axis. Particularly, the These patients are concentrated in the Mediterranean area, southern Ecuador, and South America, with a similar gender distribution [10]. The main features of the included studies are summarized in Table 1.…”

Nutrients and Pathways that Regulate Health Span and Life Span

“…The number of known and/or published LS patients is around 350. Most cases have been reported from the Mediterranean region and Southern Ecuador, and a few cases from South America, as recently reviewed [ 59 , 60 , 61 ]. LS is characterized by insensitivity to GH.…”

“…The biochemical features typical of LS patients are high serum level of GH and low free IGF1 concentrations. People affected by LS are characterized by dwarfism and obesity and have a tendency to develop hyperlipidemia, but surprisingly have a very low risk to manifest aging-related pathologies such as diabetes and cancer [ 59 , 62 , 63 ]. Additionally, other studies in humans showed a positive association between low IGF1 activity and longevity [ 64 ].…”

O sequenciamento completo do exoma deve ser a primeira abordagem genético-molecular para crianças com baixa estatura sindrômica sem diagnóstico clínico

“…Subsequentemente, defeitos no gene do receptor de GH (GHR, MIM*600946) também foram descritos como causadores da Síndrome de Laron (MIM#262500), uma forma completa de Insensibilidade ao GH, além de formas parciais desta resistência hormonal (MIM#604271) 38,42 .…”