Laron syndrome; Growth hormone insensitivity syndrome; Growth hormone receptor deficiency - GHR gene
Laron syndrome, also known as growth hormone insensitivity syndrome or growth hormone receptor deficiency, is an autosomal recessive disorder characterized by significant short stature, associated with normal, or high, concentrations of growth hormone (GH) in serum, and low concentrations of IGF-1 (insulin-like growth factor-1).
The signs and characteristics of the disease include short stature, delayed bone age, prominent forehead, depressed nasal bridge, low jaw development, trunk obesity, small penis and, occasionally, blue sclerotics and hip degeneration. Some affected patients have limited elbow extension and a sharp voice. Other characteristics of Laron syndrome include reduced strength and muscular endurance, hypoglycemia in childhood, thin and fragile hair, and dental anomalies.
This process is due to mutations in the GHR (growth hormone receptor) gene, located on the short arm of chromosome 5 (5p13.1-p12). This gene belongs to the superfamily of cytokine receptors that depend on JAK tyrosine kinases for the activation of STAT and other signaling pathways. More specifically, this gene encodes a member of type I of the cytokine receptor family, which is a transmembrane receptor for growth hormone. The binding of growth hormone to the receptor results in the dimerization of the receptor and the activation of an intracellular and intracellular signal transduction pathway that leads to growth.
More than 70 mutations in the GHR gene responsible for Laron syndrome have been identified. These changes result in a decrease in the concentration of GHBP (carrier protein of GH: structurally identical to the extracellular domain of GHR) and an abnormal production of IGF-1. This fact causes the dysfunction of the growth hormone receptor. It is believed that an exaggerated rate of growth hormone (GH) production causes a lack of negative regeneration due to IGF1 deficiency. Reduced insulin concentrations have also been observed in affected people.
This disease is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have the mutations so that the alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Some cases have been related to an autosomal dominant inheritance, which means that having a copy of an altered gene in each cell is enough to cause the disease.
Tests carried out in IVAMI: in IVAMI we perform the detection of mutations associated with the Laron syndrome, by means of the complete PCR amplification of the exons of the GHR gene, and their subsequent sequencing.
Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).