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 an increased sensitivity to insulin which means that they
are less likely to develop diabetes mellitus type 2 and possibly
cancer as well. It can be treated with injections of recombinant
1 Clinical characteristics
8 Homo floresiensis
9 See also
11 External links
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. The breasts of females reach normal size, and in
some are large in relation to body size. It has been suggested that
hyperprolactinemia may contribute to the enlarged breast size.
Seizures are frequently seen secondary to hypoglycemia. Some genetic
variations decrease intellectual capacity.
Laron syndrome patients
also do not develop acne, except temporarily during treatment with
IGF-1 (if performed).
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.
Laron syndrome has an autosomal recessive pattern of inheritance.
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.
A related condition involving postreceptor insensitivity to growth
hormone has been associated with STAT5B.
This section is empty. You can help by adding to it. (July 2017)
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, purchased by Ipsen, was approved by the US Food and Drug
Administration in August 2005 for replacing
IGF-1 in patients who are
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
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, after selling
its protein production facility, can no longer develop proteins, thus
can no longer manufacture IPLEX as of a statement released in July
Laron syndrome have strikingly low rates of cancer and
diabetes, although they appear to be at increased risk of accidental
death due to their stature.
The majority of reported cases of
Laron syndrome have been in people
with Semitic origins, almost all of them being
Jews or assimilated
descendants of Jews.
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
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 emigration 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.
It is named after Zvi Laron, 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.
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.
^ Bartke A, Sun LY, Longo V. Somatotropic Signaling: Trade-Offs
Between Growth, Reproductive Development, and Longevity. Physiological
Reviews. 2013;93(2):571-598. doi:10.1152/physrev.00006.2012.
^ Laron Z, Ginsberg S, Lilos P, Arbiv M, Vaisman N (2006). "Body
composition in untreated adult patients with
Laron syndrome (primary
GH insensitivity)". Clin. Endocrinol. 65 (1): 114–7.
doi:10.1111/j.1365-2265.2006.02558.x. PMID 16817829.
^ Laron, Zvi (2004). "Laron Syndrome (Primary Growth Hormone
Resistance or Insensitivity): The Personal Experience 1958–2003".
The Journal of Clinical
Endocrinology & Metabolism. 89 (3):
1031–1044. doi:10.1210/jc.2003-031033. ISSN 0021-972X.
^ a b 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, 255.
^ 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.
^ a b Guevara-Aguirre, J; Balasubramanian, P; Guevara-Aguirre, M; Wei,
M; Madia, F; Cheng, CW; Hwang, D; Martin-Montalvo, A; et al. (2011).
Hormone Receptor Deficiency Is Associated with a Major
Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans".
Science Translational Medicine. 3 (70): 70ra13.
doi:10.1126/scitranslmed.3001845. PMC 3357623 .
^ a b Bai, Nina. "Defective Growth
Gene in Rare
Stunts Cancer and Diabetes". Scientific American. Retrieved 17
^ Winerman, Lea. "Study:
Gene May Offer Protection From
Cancer, Diabetes". PBS. Retrieved 17 February 2011.
^ a b c d Wade, Nicholas (17 February 2011). "Ecuadorean Villagers May
Hold Secret to Longevity". The New York Times. ISSN 0362-4331.
Retrieved 17 February 2011.
^ Hwa V, Camacho-Hübner C, Little BM, et al. (2007). "Growth hormone
insensitivity and severe short stature in siblings: a novel mutation
at the exon 13-intron 13 junction of the STAT5b gene". Horm. Res. 68
(5): 218–24. doi:10.1159/000101334. PMID 17389811.
Increlex (mecasermin)". Centerwatch.com. Retrieved 21 Nov
^ Kemp, S.F. "Mecasermin rinfabate". Thomson Reuters. Retrieved 5
^ Meyer, Robert. "Approval letter (Mecasermin rinfabate)" (PDF). FDA.
Retrieved 5 March 2011.
^ "Insmed Provides Update on Supply of IPLEX(TM)". Retrieved 25 Aug
^ synd/2825 at Who Named It?
^ Laron Z, Pertzelan A, Mannheimer S (1966). "Genetic pituitary
dwarfism with high serum concentration of growth hormone—a new
inborn error of metabolism?". Isr. J. Med. Sci. 2 (2): 152–5.
^ Laron Z (2004). "
Laron syndrome (primary growth hormone resistance
or insensitivity): the personal experience 1958–2003". J. Clin.
Endocrinol. Metab. 89 (3): 1031–44. doi:10.1210/jc.2003-031033.
^ Hershkovitz I, Kornreich L, Laron Z (2007). "Comparative skeletal
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.
^ Culotta E (2007). "Paleoanthropology. The fellowship of the hobbit".
Science. 317 (5839): 740–742. doi:10.1126/science.317.5839.740.
^ 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.
V · T · D
OMIM: 262500 245590
Laron syndrome at the US National Library of Medicine Medical Subject
Diseases of the endocrine system (E00–E35, 240–259)
MODY 1 2 3 4 5 6
insulin receptor (Rabson–Mendenhall syndrome)
beta cell (Hyperinsulinism)
G cell (Zollinger–Ellison syndrome)
CRH (Tertiary adrenal insufficiency)
vasopressin (Neurogenic diabetes insipidus)
Pituitary ACTH hypersecretion
general (Nelson's syndrome)
Growth hormone deficiency
ACTH deficiency/Secondary adrenal insufficiency
posterior (Neurogenic diabetes insipidus)
Empty sella syndrome
Euthyroid sick syndrome
Thyroid hormone resistance
Familial dysalbuminemic hyperthyroxinemia
Toxic nodular goitre
Toxic multinodular goiter
Osteitis fibrosa cystica
aldosterone: Hyperaldosteronism/Primary aldosteronism
Glucocorticoid remediable aldosteronism
Cushing's syndrome (Pseudo-Cushing's syndrome)
sex hormones: 21α CAH
sex hormones: 17α CAH
ovarian: Polycystic ovary syndrome
Premature ovarian failure
17β-hydroxysteroid dehydrogenase deficiency
aromatase excess syndrome
Androgen receptor (Androgen insensitivity syndrome)
Hypogonadism (Delayed puberty)
Postorgasmic illness syndrome
Autoimmune polyendocrine syndrome multiple
Multiple endocrine neoplasia
Cell surface receptor
Cell surface receptor deficiencies
G protein-coupled receptor
Congenital hypothyroidism 1)
LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia,
Male-limited precocious puberty)
FSHR (Follicle-stimulating hormone insensitivity, XX gonadal
GnRHR (Gonadotropin-releasing hormone insensitivity)
EDNRB (ABCD syndrome,
Waardenburg syndrome 4a, Hirschsprung's disease
Nephrogenic diabetes insipidus 1)
PTGER2 (Aspirin-induced asthma)
PTH1R (Jansen's metaphyseal chondrodysplasia)
CASR (Familial hypocalciuric hypercalcemia)
Familial exudative vitreoretinopathy
Familial exudative vitreoretinopathy 1)
ROR2 (Robinow syndrome)
FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome,
Crouzon syndrome, Jackson–Weiss syndrome)
FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia,
INSR (Donohue syndrome
NTRK1 (Congenital insensitivity to pain with anhidrosis)
KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
Persistent Müllerian duct syndrome
Persistent Müllerian duct syndrome II)
TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic
TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
Leber's congenital amaurosis 1)
Type I cytokine receptor: GH (Laron syndrome)
Surfactant metabolism dysfunction 4)
MPL (Congenital amegakaryocytic thrombocytopenia)
TNFRSF1A (TNF receptor associated periodic syndrome)
Selective immunoglobulin A deficiency
Selective immunoglobulin A deficiency 2)
TNFRSF5 (Hyper-IgM syndrome type 3)
Autoimmune lymphoproliferative syndrome 1A)
LRP2 (Donnai–Barrow syndrome)
LRP4 (Cenani–Lenz syndactylism)
LRP5 (Worth syndrome,
Familial exudative vitreoretinopathy
Familial exudative vitreoretinopathy 4,
LDLR (LDLR Familial hypercholesterolemia)
Immunoglobulin superfamily: AGM3, 6
Junctional epidermolysis bullosa with pyloric atresia
EDAR hypohidrotic ectodermal dysplasia)
PTCH1 (Nevoid basal-cell carcinoma syndrome)
BMPR1A juvenile polyposis syndrome)
IL2RG (X-linked severe combined immunodeficiency)