Laron syndrome

Laron syndrome
Other namesgenetic pituitary dwarfism (1966), Laron dwarfism (1973), Laron-type dwarfism (1984), growth hormone insensitivity (1994), hereditary somatomedin deficiency, growth hormone receptor deficiency (GHRD)(1999)[1]
Growth hormone
SpecialtyEndocrinology, Medical Genetics, Pediatrics
SymptomsShort stature, truncal obesity, facial dysmorphism[2]
Usual onsetPresent at birth
DurationLifelong
CausesAutosomal recessive growth hormone receptor gene mutation (chromosome 5)[2]
Risk factorsHypoglycemia, seizures, reduced intellectual capacity, osteopenia[2]
Differential diagnosisSTAT5b, IGF1 gene mutation, ALS deficiency, IGF-1 receptor mutation, familial short stature, malnutrition, hepatic disease, congenital growth delay, hypopituitarism[1]
TreatmentIGF-1, Mecasermin[3]
Frequency1–9 / 1,000,000 (approximately 250 known cases worldwide) [4][5]

Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin-C) production in response to growth hormone (GH; hGH; somatotropin).[6] It is usually caused by inherited growth hormone receptor (GHR) mutations.[2][6]

Affected individuals classically present with short stature between −4 and −10 standard deviations below median height, obesity, craniofacial abnormalities, micropenis, low blood sugar, and low serum IGF-1 despite elevated basal serum GH.[7][5][8]

LS is a very rare condition with a total of 250 known individuals worldwide.[4][5] The genetic origins of these individuals have been traced back to Mediterranean, South Asian, and Semitic ancestors, with the latter group comprising the majority of cases.[5] Molecular genetic testing for growth hormone receptor gene mutations confirms the diagnosis of LS, but clinical evaluation may include laboratory analysis of basal GH, IGF-1 and IGFBP levels, GH stimulation testing, and/or GH trial therapy.

People with LS are unresponsive to growth hormone therapy; the disease is instead treated mainly with recombinant IGF-1, Mecasermin.[3]

Evidence has suggested that people with Laron syndrome have a reduced risk of developing cancer and diabetes mellitus type II, with a significantly reduced incidence and delayed age of onset of these diseases compared to their unaffected relatives.[9][10] The molecular mechanisms of increased longevity and protection from age-related disease among people with LS is an area of active investigation.[11]

  1. ^ a b Laron Z, Kopchick J (25 November 2010). Laron Syndrome - From Man to Mouse: Lessons from Clinical and Experimental Experience. Springer Science & Business Media. pp. 3–6. ISBN 978-3-642-11183-9. Retrieved 10 November 2020.
  2. ^ a b c d Hamosh A, O'Neill M, Phillips J, McKusick V. "# 262500 LARON SYNDROME". omim.org. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. Retrieved 10 November 2020.
  3. ^ a b Grimberg A, DiVall SA, Polychronakos C (2016). "Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency". Hormone Research in Paediatrics. 86 (6): 361–397. doi:10.1159/000452150. PMID 27884013. S2CID 5798925.
  4. ^ a b Leger J. "ORPHA:633". orpha.net. Retrieved 30 October 2020.
  5. ^ a b c d Rosenbloom AL (13 November 2019). "Growth Hormone Resistance". Medscape Reference. Archived from the original on 31 October 2020. Retrieved 3 November 2020.
  6. ^ a b Laron Z (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. PMID 15001582.
  7. ^ 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. S2CID 11524548.
  8. ^ Murray PG, Clayton PE (16 November 2016). Disorders of Growth Hormone in Childhood. MDText.com, Inc. PMID 25905205. Retrieved 3 November 2020.
  9. ^ Laron Z, Kopchick J (25 November 2010). Laron Syndrome - From Man to Mouse: Lessons from Clinical and Experimental Experience. Springer Science & Business Media. pp. 339, 341. ISBN 978-3-642-11183-9.
  10. ^ Laron Z, Kauli R, Lapkina L, Werner H (2017). "IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome". Reviews in Mutation Research. 772 (123–133): 123–133. doi:10.1016/j.mrrev.2016.08.002. PMID 28528685.
  11. ^ Werner H, Lapkina-Gendler L, Laron Z (2017). "Fifty years on: New lessons from the laron syndrome". Israel Medical Association Journal. 19 (1): 6–7. PMID 28457105.
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