Laron syndrome
Encyclopedia
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
.
, the Israeli researcher who, with A. Pertzelan and S. Mannheimer, first reported the condition in 1966, based upon observations which began in 1958.
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 gene
tic investigations have shown that this disorder is mainly associated with mutation
s 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.
A related condition involving postreceptor insensitivity to growth hormone has been associated with STAT5B
.
). Physical symptoms include: prominent forehead, depressed nasal bridge, under-development of mandible, truncal obesity
and a very small penis
. Seizures are frequently secondary to hypoglycemia
. Some genetic variations have an impact upon intellectual capacity.
The majority of reported cases have been of Arabic or Semitic origin, with numerous patients in Israel
, Saudi Arabia
, Egypt
, Iraq
, and remote villages in Ecuador
with Sephardic
roots.
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.
to be effective.
IPLEX (Mecasermin rinfabate) is composed of recombinant human IGF-1 (rhIGF-1) and its binding protein IGFBP-3. It was FDA approved in 2005 for treatment of primary IGF-1 deficiency or GH gene deletion. Side effects from IPLEX are hypoglycemia.
represented a population with widespread Laron syndrome. This hypothesis has received criticism and is unconfirmed.
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
disorder characterized by an insensitivity to growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
(GH), caused by a variant of the growth hormone receptor
Growth hormone receptor
Growth hormone receptor is a protein that in humans is encoded by the GHR gene. GHR orthologs have been identified in most mammals.-Interactions:...
. It causes short stature
Short stature
Short stature refers to a height of a human being which is below expected. Shortness is a vague term without a precise definition and with significant relativity to context...
and a resistance to diabetes and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
Eponym
It is named after Zvi LaronZvi Laron
Zvi Laron is an Israeli paediatric endocrinologist, born in Cernăuţi, Romania, a professor emeritus at Tel Aviv University.In 1966, he described the type of dwarfism later called Laron syndrome...
, the Israeli researcher who, with A. Pertzelan and S. Mannheimer, first reported the condition in 1966, based upon observations which began in 1958.
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
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, has been termed Laron syndrome.
Pathophysiology
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
tic investigations have shown that this disorder is mainly associated with mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the gene for the GH receptor. These can result in defective hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
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
Insulin-like growth factor
The insulin-like growth factors are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment...
(IGF-1) and its principal carrier protein
Carrier protein
Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...
, insulin-like growth factor binding protein 3.
A related condition involving postreceptor insensitivity to growth hormone has been associated with STAT5B
STAT5B
Signal transducer and activator of transcription 5B is a protein that in humans is encoded by the STAT5B gene. STAT5B orthologs have been identified in most placentals for which complete genome data are available.-Interactions:...
.
Clinical characteristics
The principal feature of Laron syndrome is abnormally short stature (dwarfismDwarfism
Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....
). Physical symptoms include: prominent forehead, depressed nasal bridge, under-development of mandible, truncal obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
and a very small penis
Micropenis
Micropenis is an unusually small penis. A common criterion is a dorsal erect penile length of at least 2.5 standard deviations smaller than the mean human penis size. The condition is usually recognized shortly after birth...
. Seizures are frequently secondary to hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
. Some genetic variations have an impact upon intellectual capacity.
The majority of reported cases have been of Arabic or Semitic origin, with numerous patients in Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
, Saudi Arabia
Saudi Arabia
The Kingdom of Saudi Arabia , commonly known in British English as Saudi Arabia and in Arabic as as-Sa‘ūdiyyah , is the largest state in Western Asia by land area, constituting the bulk of the Arabian Peninsula, and the second-largest in the Arab World...
, Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
, Iraq
Iraq
Iraq ; officially the Republic of Iraq is a country in Western Asia spanning most of the northwestern end of the Zagros mountain range, the eastern part of the Syrian Desert and the northern part of the Arabian Desert....
, and remote villages in Ecuador
Ecuador
Ecuador , officially the Republic of Ecuador is a representative democratic republic in South America, bordered by Colombia on the north, Peru on the east and south, and by the Pacific Ocean to the west. It is one of only two countries in South America, along with Chile, that do not have a border...
with Sephardic
Sephardi Jews
Sephardi Jews is a general term referring to the descendants of the Jews who lived in the Iberian Peninsula before their expulsion in the Spanish Inquisition. It can also refer to those who use a Sephardic style of liturgy or would otherwise define themselves in terms of the Jewish customs and...
roots.
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.
Treatment
Administration of GH has no effect on IGF-1 production, therefore treatment is mainly by biosynthetic IGF-1. IGF-1 must be taken before pubertyPuberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
to be effective.
IPLEX (Mecasermin rinfabate) is composed of recombinant human IGF-1 (rhIGF-1) and its binding protein IGFBP-3. It was FDA approved in 2005 for treatment of primary IGF-1 deficiency or GH gene deletion. Side effects from IPLEX are hypoglycemia.
Homo floresiensis
Recent publications have proposed that Homo floresiensisHomo floresiensis
Homo floresiensis is a possible species, now extinct, in the genus Homo. The remains were discovered in 2003 on the island of Flores in Indonesia. Partial skeletons of nine individuals have been recovered, including one complete cranium...
represented a population with widespread Laron syndrome. This hypothesis has received criticism and is unconfirmed.