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].

• 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]

  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]

• 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]

• Skeletal Dysplasia

  Another possibility is an inherited skeletal dysplasia; However, the normal skeletal survey renders this unlikely. Next in sequence should be targeted endocrine investigations. [medicaljoyworks.com]

  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]

  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 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]

• Osteophyte

  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]

• Alopecia

  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]

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].

• EEG Slowing

  The sleep microstructure (cyclic alternating pattern: CAP) showed significantly higher EEG slow oscillations (A1%) in NREM sleep, both during IGF-1 therapy and wash-out. [ncbi.nlm.nih.gov]

• Fasting Hypoglycemia

  Approximately 50% of infants and children with Laron syndrome present with overt symptoms of hypoglycemia (especially fasting hypoglycemia), including seizures. [accessanesthesiology.mhmedical.com]

  Metabolic abnormalities include fasting hypoglycemia and hypercholesterolemia. The underlying metabolic defect lies in the lack of responsiveness of the target organs to endogenous GH. [pubs.sciepub.com]

• Liver Biopsy

  The etiopathogenesis was disclosed by 2 liver biopsies demonstrating a defect in the GH receptor. Subsequent investigations demonstrated deletions or mutations in the GHR gene. [ncbi.nlm.nih.gov]

  Direct evidence of a defect in the GHR came in 1984 when Laron and colleagues demonstrated that hepatic microsomes obtained by liver biopsy of 2 patients did not bind radiolabeled GH. [flipper.diff.org]

  In 1984, it was proven by liver biopsy that GH does not bind to its receptors and therefore is unable to generate IGF-1 [ 10 ]. [pubs.sciepub.com]

  In 1984, it was proven by liver biopsy that GH does not bind to its receptors and therefore is unable to generate IGF-1 [ 8 ]. [doi.org]

Growth velocity decreased in the 6-12th month of combined treatment (0.9 cm/6 months), and treatment was suspended. [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]

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]

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]

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]

Aging, Baltimore, MD 21224, USA. 6 Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide–Consejo Superior de Investigaciones Cientificas and Centre for Biomedical Research on Rare Diseases, ISCIII, E-41013 Sevilla, Spain. 7 Division of Epidemiology [stm.sciencemag.org]

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]

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.