|Classification and external resources|
Laron's syndrome, or Laron-type dwarfism, is an autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), usually caused by a mutant growth hormone receptor. It causes short stature and a resistance to insulin or even a rare form of diabetes mellitus type 2 and cancer. It can be treated with injections of recombinant IGF-1.
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 among the country's diverse Jewish population composed of Jews from around the world, as well as patients outside Israel originally from communities of the Jewish diaspora, such as Egypt and Iraq. There is also a disproportionate number of sufferers found in remote villages in the South American country of Ecuador who are descended from colonial-era Jewish-origin New Christian conversos (Sephardi Jews who themselves, or whose forebears, had been compelled to convert to Catholicism back in Spain) who had covertly migrated to Ecuador during the Spanish Conquest despite the Spanish Crown's prohibition of their immigration to its colonies and territories as a result of the Inquisition.
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 micropenis in males. In spite of very low levels of serum IGF-1, the breasts of females reach normal size, and may be large in relation to body size. It has been suggested that hyperprolactinemia may contribute to this. 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.
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.
Recent publications have proposed that Homo floresiensis represented a population with widespread Laron syndrome. This is only one of several competing hypotheses, and has received criticism as insufficient to explain the "range features observed in H. Floresiensis".
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- synd/2825 at Who Named It?
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- Zvi Laron; J. Kopchick (25 November 2010). Laron Syndrome - From Man to Mouse: Lessons from Clinical and Experimental Experience. Springer Science & Business Media. pp. 253–. ISBN 978-3-642-11183-9.
- Shevah O, Kornreich L, Galatzer A, Laron Z (2005). "The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities". Horm. Metab. Res. 37 (12): 757–60. doi:10.1055/s-2005-921097. PMID 16372230.
- Bai, Nina. "Defective Growth Gene in Rare Dwarfism Disorder Stunts Cancer and Diabetes". Scientific American. Retrieved 17 February 2011.
- Winerman, Lea. "Study: Dwarfism Gene May Offer Protection From Cancer, Diabetes". PBS. Retrieved 17 February 2011.
- "Increlex (mecasermin)". Centerwatch.com. Retrieved 21 Nov 2014.
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- Meyer, Robert. "Approval letter (Mecasermin rinfabate)" (PDF). FDA. Retrieved 5 March 2011.
- Hershkovitz I, Kornreich L, Laron Z (2007). "Comparative skeletal features between Homo floresiensis and patients with primary growth hormone insensitivity (Laron syndrome)". Am. J. Phys. Anthropol. 134 (2): 198–208. doi:10.1002/ajpa.20655. PMID 17596857.
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- Aiello, Leslie C. (2010). "Five years ofHomo floresiensis". American Journal of Physical Anthropology 142: NA–NA. doi:10.1002/ajpa.21255. ISSN 0002-9483. PMID 20229502.
- Laron syndrome at the US National Library of Medicine Medical Subject Headings (MeSH)
- Secrets of a Long Life, a documentary about studies on Ecuadorians with Laron syndrome. Arte France (2013).