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Laron-type isolated somatotropin defect

MedGen UID:
78776
Concept ID:
C0271568
Disease or Syndrome
Synonyms: Growth hormone binding protein deficiency or dysfunction; Growth hormone receptor deficiency; Growth hormone receptor deficiency or dysfunction; Laron dwarfism; Laron Syndrome; Laron type pituitary dwarfism I; Pituitary Dwarfism II
SNOMED CT: Laron syndrome (38196001); Laron-type isolated somatotropin defect (38196001); Laron-type dwarfism (38196001); Laron dwarfism (38196001); Laron-type pituitary dwarfism (38196001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GHR (5p13.1-12)
 
Monarch Initiative: MONDO:0009877
OMIM®: 262500
Orphanet: ORPHA633

Definition

Laron syndrome is an autosomal recessive disorder characterized by marked short stature that results from failure to generate insulin-like growth factor I (IGF1; 147440) in response to growth hormone (GH; 139250). GH levels are normal or increased. The disorder is caused by dysfunction of the growth hormone receptor. A Laron syndrome-like phenotype associated with immunodeficiency (245590) is caused by a postreceptor defect, i.e., mutation in the STAT5B gene (604260). Patients with mutations in the GHR gene that cause only partial insensitivity to growth hormone have a form of short stature (604271). [from OMIM]

Additional description

From MedlinePlus Genetics
Laron syndrome is a rare form of short stature that results from the body's inability to use growth hormone, a substance produced by the brain's pituitary gland that helps promote growth. Affected individuals are close to normal size at birth, but they experience slow growth from early childhood that results in very short stature. If the condition is not treated, adult males typically reach a maximum height of about 4.5 feet; adult females may be just over 4 feet tall.

Other features of untreated Laron syndrome include reduced muscle strength and endurance, low blood glucose levels (hypoglycemia) in infancy, small genitals and delayed puberty, hair that is thin and fragile, and dental abnormalities. Many affected individuals have a distinctive facial appearance, including a protruding forehead, a sunken bridge of the nose (saddle nose), and a blue tint to the whites of the eyes (blue sclerae). Affected individuals have short limbs compared to the size of their torso, as well as small hands and feet. Adults with this condition tend to develop obesity. However, the signs and symptoms of Laron syndrome vary, even among affected members of the same family.

Studies suggest that people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes. Affected individuals appear to develop these common diseases much less frequently than their unaffected relatives, despite having obesity (a risk factor for both cancer and type 2 diabetes). However, people with Laron syndrome do not seem to have an increased lifespan compared with their unaffected relatives.  https://medlineplus.gov/genetics/condition/laron-syndrome

Clinical features

From HPO
Limb undergrowth
MedGen UID:
116086
Concept ID:
C0239399
Finding
Limb shortening because of underdevelopment of one or more bones of the extremities.
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
High pitched voice
MedGen UID:
66836
Concept ID:
C0241703
Finding
An abnormal increase in the pitch (frequency) of the voice.
Abnormal joint morphology
MedGen UID:
893053
Concept ID:
C0240083
Finding
An abnormal structure or form of the joints, i.e., one or more of the articulations where two bones join.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Small face
MedGen UID:
343376
Concept ID:
C1855538
Finding
A face that is short and narrow.
Delayed menarche
MedGen UID:
184929
Concept ID:
C0949173
Disease or Syndrome
First period after the age of 15 years.
Decreased serum insulin-like growth factor 1
MedGen UID:
892792
Concept ID:
C4072897
Finding
A reduced level of insulin-like growth factor 1 (IGF1) in the blood circulation.
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLaron-type isolated somatotropin defect
Follow this link to review classifications for Laron-type isolated somatotropin defect in Orphanet.

Professional guidelines

PubMed

Savage MO
Endocr Dev 2013;24:138-49. Epub 2013 Feb 1 doi: 10.1159/000342578. PMID: 23392102
Wit JM
Pediatr Endocrinol Rev 2011 Sep;9 Suppl 1:538-40. PMID: 22423513
Backeljauw P, Bang P, Clayton PE, Geffner M, Woods KA
Pediatr Endocrinol Rev 2010 Feb;7 Suppl 1:154-71. PMID: 20463651

Recent clinical studies

Etiology

Young J, Bell S, Qian Y, Hyman C, Berryman DE
Rev Endocr Metab Disord 2021 Mar;22(1):17-29. Epub 2020 Oct 10 doi: 10.1007/s11154-020-09600-6. PMID: 33037595Free PMC Article
Werner H, Laron Z
Mol Cell Endocrinol 2020 Dec 1;518:111003. Epub 2020 Sep 10 doi: 10.1016/j.mce.2020.111003. PMID: 32919021
Boguszewski CL, Boguszewski MCDS
Endocr Rev 2019 Apr 1;40(2):558-574. doi: 10.1210/er.2018-00166. PMID: 30500870
Janecka A, Kołodziej-Rzepa M, Biesaga B
In Vivo 2016 Jul-Aug;30(4):375-81. PMID: 27381597
Kurtoğlu S, Hatipoglu N
J Endocrinol Invest 2016 Jan;39(1):19-28. Epub 2015 Jun 11 doi: 10.1007/s40618-015-0327-2. PMID: 26062520

Diagnosis

Miller BS, Rogol AD, Rosenfeld RG
Horm Res Paediatr 2022;95(6):619-630. Epub 2022 Nov 29 doi: 10.1159/000527123. PMID: 36446332
Guevara-Aguirre J, Guevara A, Palacios I, Pérez M, Prócel P, Terán E
Growth Horm IGF Res 2018 Feb;38:34-38. Epub 2017 Dec 12 doi: 10.1016/j.ghir.2017.12.006. PMID: 29395968
Kurtoğlu S, Hatipoglu N
J Endocrinol Invest 2016 Jan;39(1):19-28. Epub 2015 Jun 11 doi: 10.1007/s40618-015-0327-2. PMID: 26062520
Guleria S, Sharma J, Kaushik SL
J Postgrad Med 2014 Jul-Sep;60(3):322-3. doi: 10.4103/0022-3859.138816. PMID: 25121377
Wit JM
Pediatr Endocrinol Rev 2011 Sep;9 Suppl 1:538-40. PMID: 22423513

Therapy

Miller BS, Rogol AD, Rosenfeld RG
Horm Res Paediatr 2022;95(6):619-630. Epub 2022 Nov 29 doi: 10.1159/000527123. PMID: 36446332
Bang P, Woelfle J, Perrot V, Sert C, Polak M
Eur J Endocrinol 2021 Feb;184(2):267-276. doi: 10.1530/EJE-20-0325. PMID: 33434161Free PMC Article
Boguszewski CL, Boguszewski MCDS
Endocr Rev 2019 Apr 1;40(2):558-574. doi: 10.1210/er.2018-00166. PMID: 30500870
Bright GM
Growth Horm IGF Res 2016 Jun;28:62-5. Epub 2016 Jan 18 doi: 10.1016/j.ghir.2016.01.002. PMID: 26822565
Kurtoğlu S, Hatipoglu N
J Endocrinol Invest 2016 Jan;39(1):19-28. Epub 2015 Jun 11 doi: 10.1007/s40618-015-0327-2. PMID: 26062520

Prognosis

Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
Bang P, Woelfle J, Perrot V, Sert C, Polak M
Eur J Endocrinol 2021 Feb;184(2):267-276. doi: 10.1530/EJE-20-0325. PMID: 33434161Free PMC Article
Guevara-Aguirre J, Teran E, Lescano D, Guevara C, Guevara A, Saavedra J, Procel P, Wasserfall C, Gavilanes AWD
Growth Horm IGF Res 2020 Aug-Oct;53-54:101339. Epub 2020 Jul 28 doi: 10.1016/j.ghir.2020.101339. PMID: 32763832
Bright GM
Growth Horm IGF Res 2016 Jun;28:62-5. Epub 2016 Jan 18 doi: 10.1016/j.ghir.2016.01.002. PMID: 26822565
Backeljauw P, Bang P, Clayton PE, Geffner M, Woods KA
Pediatr Endocrinol Rev 2010 Feb;7 Suppl 1:154-71. PMID: 20463651

Clinical prediction guides

Backeljauw PF, Andrews M, Bang P, Dalle Molle L, Deal CL, Harvey J, Langham S, Petriczko E, Polak M, Storr HL, Dattani MT
Orphanet J Rare Dis 2023 Oct 7;18(1):312. doi: 10.1186/s13023-023-02928-7. PMID: 37805563Free PMC Article
Guevara-Aguirre J, Peña G, Acosta W, Pazmiño G, Saavedra J, Soto L, Lescano D, Guevara A, Gavilanes AWD
Endocr Relat Cancer 2023 Oct 1;30(10) Epub 2023 Aug 14 doi: 10.1530/ERC-22-0402. PMID: 37428642
Guevara-Aguirre J, Guevara A, Bahamonde M
Growth Horm IGF Res 2018 Feb;38:44-48. Epub 2017 Dec 20 doi: 10.1016/j.ghir.2017.12.012. PMID: 29306561
Bright GM
Growth Horm IGF Res 2016 Jun;28:62-5. Epub 2016 Jan 18 doi: 10.1016/j.ghir.2016.01.002. PMID: 26822565
Wit JM, de Luca F
Growth Horm IGF Res 2016 Jun;28:57-61. Epub 2015 Nov 30 doi: 10.1016/j.ghir.2015.11.005. PMID: 26670721

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