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Laron Syndrome


Characterized by a very short stature, facial changes, and obesity, Laron syndrome is an autosomal recessive genetic disorder in which insensitivity to growth hormone by tissues is the main pathological entity. Mutations in the growth hormone gene have shown to be responsible for the disorder, but the diagnosis can be made only after a thorough clinical and laboratory workup.


The clinical presentation of patients suffering from Laron syndrome, occurring due to growth hormone (GH) insensitivity, is diverse, but the two most important features are dwarfism and obesity [1] [2]. The majority of patients exhibit short stature from birth, and a progressive deficit in growth and development throughout childhood leads to finite body heights between 4 and 10 height standard deviations (SDs) below the average for appropriate age [1]. In addition, very small hands and feet (known as acromicria) are observed, as well as short limbs compared to the size of the trunk [1]. Obesity is progressive, despite the fact that the caloric intake is normal or even reduced, and occurs on the grounds of reduced muscle and bone content [1]. It often predisposes patients to sleep apnea, skin wrinkling and joint pain as a result of poor muscle strength, which may be quite debilitating [1] [2] [3]. Genital and hormonal abnormalities, such as hypogonadism and underdevelopment of the genital organs (or hypogenitalism, manifesting as micropenis, small testes, and reduced ovarian size, respectively) are frequent findings in children suffering from this genetic disorder. Moreover, puberty is often delayed, and secondary sexual characteristics typically develop later in adolescence [1] [3] [4]. Facial changes, including protrusion of the forehead, a saddle nose, hypoplasia of the mandible and other facial bones, thin hair and delayed teething are common features as well [1] [5]. Delayed nail growth and blue sclerae may also be present [1].

Thyroid Nodule
  • Thyroid ultrasonography showed a reduced thyroid size (right lobe transverse diameter (TD) 11 mm and anteroposterior diameter (APD) 13 mm; left lobe TD 10 mm and APD 9 mm) with normal echotexture and without thyroid nodules.[ncbi.nlm.nih.gov]
Short Stature in Children
  • The studies enrolled a total of 71 children suffering from extreme short stature; all children exhibited symptoms of Primary IGFD, including slow growth rates, low IGF-1 serum concentrations, and normal growth hormone secretion.[centerwatch.com]
  • Richter-Unruh A, Knauer-Fischer S, Kaspers S, Albrecht B, Gillessen-Kaesbach G, Hauffa BP: Short stature in children with an apparently normal male phenotype can be caused by 45,X/46,XY mosaicism and is susceptible to growth hormone treatment.[doi.org]
Saddle Nose
  • They had typical appearance features of Laron syndrome such as short stature and obesity, with protruding forehead, saddle nose, large eyes, sparse and thin silky hair and high-pitched voice.[ncbi.nlm.nih.gov]
  • Facial changes, including protrusion of the forehead, a saddle nose, hypoplasia of the mandible and other facial bones, thin hair and delayed teething are common features as well. Delayed nail growth and blue sclerae may also be present.[symptoma.com]
  • Upon examination she was noted to have protruded forehead, thin hair, small hands and feet, and a saddle nose. No teething defects were found, and no blue sclera was observed ( Figure 1 ).[alliedacademies.org]
  • Other features include hypoplasia of the base of the skull with small face and mandible, delayed closure of the fontanels, saddle nose, hypotrichosis, delayed dentition, tooth discoloration, crowding of defective teeth, high-pitched voice, acromicria,[whonamedit.com]
  • The siblings had typical dysmorphic facies: frontal bossing, shallow orbit with blue sclera, saddle nose, mid-face hypoplasia, thin and silky hair and pale texture of skin.[pubs.sciepub.com]
  • Here, we identified a novel homozygous substitution mutation (E42K: GAG-- AAG at codon 42 cDNA) of the GHR gene in a Chinese girl with Laron syndrome.[ncbi.nlm.nih.gov]
Systolic Murmur
  • Their cardiac examinations were normal, except for one case, who had systolic murmur at cardiac auscultation. Arrhythmia was not observed on their electrocardiograms. The echocardiograms did not show a significant congenital cardiac anomaly.[ncbi.nlm.nih.gov]
  • Young adults have various degrees of alopecia, more pronounced in males. OBJECTIVE: The aim of the present study was to investigate the effect of primary IGF-1 deficiency on hair structure.[ncbi.nlm.nih.gov]
  • […] stature due to endocrine disorder Approximate Synonyms Ateliotic dwarf Ateliotic dwarfism without insulinopenia Congenital malformation syndromes associated with short stature Constitutional short stature Dolichocephalic dwarfism Dwarfism Dwarfism, alopecia[icd9data.com]
  • Young adults have various degrees of alopecia, more pronounced in males. Objective: The aim of the present study was to investigate the effect of primary IGF-1 deficiency on hair structure.[karger.com]
Skeletal Dysplasia
  • Dysplasia Sotos Syndrome Spina Bifida Spondyloepiphyseal Dysplasia Tangiers Syndrome Trichorhinophalangeal Syndrome Trisomy 14, Mosaic Pattern Trisomy 18 Trisomy 21 trisomy 4 P , GHD, genisis of the corpus colosom, ONH Weaver Syndrome Weill Marchesani[magicfoundation.org]
  • The genetic basis of these disorders is emerging, as many skeletal dysplasia gene loci have been identified. More than half of all patients with skeletal dysplasias have a mutation at COL2A1 or FGFR3.[doi.org]
  • The cervical spine in the skeletal dysplasias and associated disorders. Pediatr Radiol 1997 ; 27 : 402 –408 Dai LY, Yuan W, Ni B, Jia LS. Os odontoideum: etiology, diagnosis and management. Surg Neurol 2000 ; 53 : 106 –109 Heick A.[ajnr.org]
  • Thoracic and lumbar osteophytes were graded on a 5-point scale. Values were compared with a control group of 20 healthy persons matched for age. RESULTS: The skeleton appeared small in all patients. No signs of osteopenia were visible.[ncbi.nlm.nih.gov]
  • Several cases of intra-cranial hypertension or papilledema have been observed.[ncbi.nlm.nih.gov]


The diagnosis of Laron syndrome can be difficult to attain without a thorough patient history and a meticulous physical examination. The autosomal recessive nature of the disorder may be the reason why it is identified almost exclusively in families with consanguineous marriages, and the majority of patients are of Middle-Eastern or Mediterranean origin [1] [2]. For this reason, the presence of similar symptoms and signs in among close relatives or siblings may be a valuable clue toward the diagnosis, whereas a complete physical examination provides sufficient clinical criteria to assume impaired growth hormone activity. Basic laboratory workup should include estimation of glucose levels, as many patients suffer from hypoglycemia, the later development of diabetes mellitus and insulin intolerance, together with serum alkaline phosphatase (ALP), creatinine, a full lipid profile, and hormonal assessment [1]. Paradoxically, growth hormone (GH) levels are normal or markedly elevated when exogenous stimulation is performed, but the values of insulin-like growth factor 1 (IGF-1) are quite low, which serves as one of the key regulators of GH activity [1]. Low IGF-1 levels are thought to explain the mild pancytopenia that is observed in patients, due to its potential role in erythropoiesis [1]. Imaging studies, such as plain radiography and computed tomography (CT), could be used to assess skeletal and soft-tissue changes, respectively. Even though the diagnosis is often made based on clinical and laboratory criteria [3] [6], genetic studies should be carried out, if possible, in order to confirm GH insensitivity [1].


  • Growth velocity decreased in the 6-12th month of combined treatment (0.9 cm/6 months), and treatment was suspended.[ncbi.nlm.nih.gov]
  • Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 /- 0.8 nmol/l (mean /- SEM), rising to 10 /- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day.[ncbi.nlm.nih.gov]
  • We describe the development of androgenization during IGF-I treatment of female LS patients.[ncbi.nlm.nih.gov]
  • Whether patients with LS are osteopenic or not, and whether they need treatment with bisphosphonates, remains uncertain.[ncbi.nlm.nih.gov]
  • Blood samples for procollagens were collected before, during and at the end of IGF-I treatment.[ncbi.nlm.nih.gov]


  • Prognosis Prognosis seems good but with age, patients may develop obesity, hypercholesterolemia and have increased risk of fractures due to osteopenia. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • Prevention - Laron syndrome Diagnosis - Laron syndrome Prognosis - Laron syndrome The long-term outlook (prognosis) for people with Laron syndrome is generally good.[checkorphan.org]
  • Prognosis With age, osteoporosis can become apparent. Patients may develop obesity, hypercholesterolemia, insulin resistance, glucose intolerance and even type II diabetes.[orpha.net]


  • Etiology The disease is due to mutations in the GHR gene (5p14-p12).[orpha.net]
  • Deletions and mutations in the growth hormone receptor (GHR) gene are the underlying etiology of Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS), an autosomal recessive disease.[ncbi.nlm.nih.gov]
  • In the present pandemics of obesity and insulin resistant diabetes mellitus (DM), the specific contribution of etiological factors such as shifts in nutritional and exercise patterns, genetic and hormonal, is subject of ongoing research.[ncbi.nlm.nih.gov]


  • Epidemiological studies have shown that LS occurs more often in consanguineous families and isolates, and it has been described in several countries in South East Asia.[ncbi.nlm.nih.gov]
  • Recent epidemiological studies have shown that patients with Laron syndrome (LS), the best-characterized entity among the congenital IGF1 deficiencies, seem to be protected from cancer development.[ncbi.nlm.nih.gov]
  • Summary Epidemiology The disease has been described in more than 250 cases and is more frequent in Semitic or Mediterranean populations. Males and females are equally affected.[orpha.net]
Sex distribution
Age distribution


  • Additional chapters examine the pathophysiology of insulin-dependent diabetes mellitus, the molecular genetics of thyroid cancer, the molecular basis of hypophosphatemic rickets, and inherited diabetes insipidus.[books.google.com]
  • The genetic basis of the syndrome is fully considered, and all aspects of the pathophysiology of IGF-I deficiency are described. Data derived from the recently generated mouse model of LS are reviewed and compared with the human LS experience.[springer.com]
  • […] reported that people with this syndrome in the Ecuadorian villages are resistant to cancer and diabetes and are somewhat protected against aging. [6] [7] [8] This is consistent with findings in mice with a defective growth hormone receptor gene. [9] Pathophysiology[en.wikipedia.org]


  • This mutation is expected to prevent the translation of the protein. We present clinical, biochemical and molecular evidence of Laron syndrome as the result of a mutation (ATG-- TTG) in the codon for the initial methionine of the GHR gene.[ncbi.nlm.nih.gov]
  • Currently, cancer prevention mainly revolves around changing lifestyle factors. According to the World Health Organisation, "at least one-third of all cancer cases are preventable".[huffingtonpost.co.uk]
  • {"duration":"3:00","description":"Rare form of genetic mutation found in dwarfism also prevents cancer and diabetes."[abcnews.go.com]



  1. Laron Z. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. J Clin Endocrinol Metab. 2004;89(3):1031-1044.
  2. Kanety H, Hemi R, Ginsberg S, et al. Total and high molecular weight adiponectin are elevated in patients with Laron syndrome despite marked obesity. Eur J Endocrinol. 2009;161(6):837-844.
  3. Phanse-Gupte SR, Khadilkar VV, Khadilkar AV. Clinical features and endocrine profile of Laron syndrome in Indian children. Indian J Endocrinol Metab. 2014;18(6):863-867.
  4. Goswami S, Ghosh S, Chowdhury S. Growth hormone insensitivity syndrome: A sensitive approach. Indian J Endocrinol Metab. 2012;16(5):817-818.
  5. Cotta OR, Santarpia L, Curtò L, et al. Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report. J Med Case Reports. 2011;5:301.
  6. Guleria S, Sharma J, Kaushik SL. Laron syndrome. J Postgrad Med. 2014;60(3):322-323.

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Last updated: 2019-06-28 12:36