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]

• 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]

• Severe Short Stature

  The proband is a 3.5 year-old Druse girl with severe short stature (height SDS -5.1), high GH (250 micrograms/l), low IGF-I (2.7 nmol/l) and IGFBP-3 (410 micrograms/l), both unresponsive to exogenous GH. [ncbi.nlm.nih.gov]

  Laron syndrome (LS) first described 50 years ago in 1966 is with few exceptions a genetic form of severe short stature, found in the majority of instances in patients originating from the Mediterranean, Middle East and South Asian regions. [atlasofscience.org]

• 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]

• Myelopathy

  Atlantoaxial instability in os odontoideum with myelopathy. Spine 1996;21:1435–1439 ↵ Zapletal J, Hekster RE, Straver JS, Wilmink JT. Atlanto-odontoid osteoarthritis: appearance and prevalence at computed tomography. [ajnr.org]

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]

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

Management and treatment Management aims at improving growth and includes treatment with daily subcutaneous injections of mecasermin, recombinant human IGF-I, and diet with adequate caloric intake. [orpha.net]

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]

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]

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]

I love the woman's reaction when you said do you know you could be the key to preventing cancer in the world. It was a lovely expression. Thank you so much, john, for the journey. [abcnews.go.com]

Prevention - Laron syndrome Diagnosis - Laron syndrome Prognosis - Laron syndrome The long-term outlook (prognosis) for people with Laron syndrome is generally good. [checkorphan.org]

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.