|Classification and external resources|
Laron syndrome, or Laron-type dwarfism, is an autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), caused by a variant of the growth hormone receptor. It causes short stature and a resistance to diabetes and cancer.
Resistance to GH was first reported by Laron in 1966. Since then, severe resistance to GH, characterized by grossly impaired growth despite normal levels of GH in serum, has been termed Laron syndrome.
Molecular genetic investigations have shown that this disorder is mainly associated with mutations in the gene for the GH receptor. These can result in defective hormone binding to the ectodomain or reduced efficiency of dimerization of the receptor after hormone occupancy. There are exceptionally low levels of insulin-like growth factor (IGF-1) and its principal carrier protein, insulin-like growth factor binding protein 3.
Numerous Laron syndrome patients are found in Israel (within its diverse Jewish population from around the world), as well as sufferers elsewhere who hail from communities of the Jewish diaspora originally from countries including Egypt and Iraq. There is also a disproportionate number of sufferers found in remote villages in the South American country of Ecuador who have ancestry that has been traced back to New Christian conversos whose Sephardi Jewish forebears had been compelled to convert to Catholicism either by force or social coercion back in Spain during the Inquisition, and then covertly migrated and settled in Ecuador during the early years of the Spanish Conquest despite the Spanish Crown's prohibition of their immigration to its colonies and territories.
Other patients include people of other Semitic non-Jewish origins, including from Saudi Arabia.
The principal feature of Laron syndrome is abnormally short stature (dwarfism). Physical symptoms include: prominent forehead, depressed nasal bridge, underdevelopment of mandible, truncal obesity and a very small penis. Seizures are frequently seen secondary to hypoglycemia. Some genetic variations decrease intellectual capacity.
In 2011, it was reported that people with this syndrome in the Ecuadorian villages are resistant to cancer and diabetes and are somewhat protected against aging. This is consistent with findings in mice with a defective growth hormone receptor gene.
Administration of GH has no effect on IGF-1 production, therefore treatment is mainly by biosynthetic IGF-1. IGF-1 must be taken before puberty to be effective. The drug product Increlex (mecasermin), developed by the company Tercica, now Genentech, was approved by the US Food and Drug Administration in August 2005 for replacing IGF-1 in patients who are deficient.
IPLEX (Mecasermin rinfabate) is composed of recombinant human IGF-1 (rhIGF-1) and its binding protein IGFBP-3. It was approved by the U.S. Food and Drug Administration (FDA) in 2005 for treatment of primary IGF-1 deficiency or GH gene deletion. Side effects from IPLEX are hypoglycemia.
IPLEX's manufacturing company, Insmed, can no longer develop proteins and can no longer manufacture IPLEX as of a statement released in January 2012.
- synd/2825 at Who Named It?
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