Laron Syndrome

Alternative Names

  • Growth Hormone Insensitivity Syndrome
  • Pituitary Dwarfism II
  • Growth Hormone Receptor Deficiency

Associated Genes

Growth Hormone Receptor
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Disorders of other endocrine glands

OMIM Number

262500

Mode of Inheritance

Autosomal recessive

Gene Map Locus

5p13-p12

Description

Laron syndrome is an autosomal recessive congenital disorder distinguished by marked short stature correlated with normal or high serum growth hormone (GH) and low serum insulin-like growth factor-1 (IGF-1) levels which fail to increase following exogenous GH administration. The disorder affects both males and females equally, with a prevalence of 1-9/1,000,000, and is more frequent in Semitic or Mediterranean populations. Worldwide, over 250 cases have been portrayed.

Patients generally retain normal intrauterine growth and birth size, however, postnatal growth is decelerated and usually disproportional with delayed bone age; adult stature ranges between -3 to -12 SD. Motor development is belated due to diminished muscle mass and newborns are often portrayed with hypoglycemia and a micropenis. Puberty is often belated, with frequent facial dysmorphism, which consists of protruding, high forehead, shallow orbits, hypoplastic nasal bridge, and small chin. Throughout infancy, sparse hair can be observed with relative obesity, delayed tooth eruption, high-pitched voice, thin bones and skin, and decreased sweating. Moreover, patients might seldom suffer from blue sclera and hip degeneration. Females suffering from Laron syndrome possess normal reproductive capability but require Cesarean delivery.

Larson syndrome is diagnosed through clinical and biological findings including the results of hormonal tests that can disclose either normal or elevated levels of GH and low IGF-1 levels, which fail to increase following exogenous GH administration. Meanwhile, for an accurate etiological diagnosis, genetic tests are employed. The differential diagnosis ought to include severe growth hormone deficiency (GHD) and growth delay as a result of IGF-I resistance, with secondary IGF-I deficiency typically as a result of nutritional difficulties or chronic pediatric diseases.

Genetic counseling can be offered to parents of an affected person prior to further pregnancy, to inform them of the risks and the accessible diagnostic techniques. Laron syndrome can be managed through treatment with daily subcutaneous injections of mecasermin, recombinant human IGF-I, and diet with sufficient caloric intake to improve patients' growth. The disease cannot be treated fully or prevented however, frequent feeding is essential to prevent hypoglycemia. Prognosis appears to be of high-quality although with age, subjects can develop obesity, hypercholesterolemia and suffer from a higher risk of fractures as a result of osteopenia.

Molecular Genetics

Laron syndrome originates due to mutations in GHR (growth hormone receptor) gene located on 5p14-p12.

Epidemiology in the Arab World

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Other Reports

Kuwait

Zaki et al. (1993) reported the first sibship in an Arab Muslim family from Kuwait and demonstrated the latest accessible recombinant human insulin-like growth factor I, which acts as a promoter of growth in children with Laron syndrome.

Palestine

Laron (1984) indicated the presence of the condition in patients of Palestinian Arab origin and a few patients from other Mediterranean countries [See also: Yemen > Laron et al., 1966; Laron, 1995].

Yemen

Laron (1995) started clinical investigations in 1958 of three siblings (two males and one female) with marked short stature. Their ages were 3.5 yr, 1.5 yr, and a newborn baby. They belonged to a consanguineous Jewish family of Yemenite origin (the parents' grandparents were first cousins). They had five older siblings of normal stature. According to their appearance, they resembled children with hypopituitarism, such as dwarfism, obesity, and severe hypoglycemia (Laron, 1995). A few years later, Laron et al. (1966) found out that the patients had very high serum hGH levels in the acromegalic range and concluded that this familial condition is most probably hereditary and could be a new syndrome involving hGH [See also: Palestine > Laron, 1984].

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