Information on the following diseases can be found in the Related Disorders section of this report:

• Coffin-Siris Syndrome
• Cockayne Syndrome

Laron syndrome is characterized by severe but proportionate short stature that is evident at birth or soon after. Along with growth retardation, there are delays in tooth eruption. There is also disproportion between the growth of the head and jaw, a saddle nose and deep-set eyes. Sexual development is slow but it does occur. The usual age of sexual maturation in boys with Laron syndrome is about 22 years of age. In females with the disorder, sexual maturation usually takes place between 16 to 19 years of age. Hands and feet are smaller than normal. Obesity and a high-pitched voice may also be present.

There are always high levels of growth hormone in the plasma of people with LTD1. A high percentage of patients have extremely low blood sugar levels (hypoglycemia) that can have very serious consequences if not treated promptly by a doctor.

Laron syndrome type I is inherited as an autosomal recessive genetic disorder. The defective gene has been traced to chromosome 5 (5p13-p12).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 5p13-p12" refers to a location between bands 13 and 12 on the short arm of chromosome 5. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Worldwide, only about 250 cases have been reported. The ethnic background for most (90%) of the reported cases is known. About 65% of cases involve persons of Middle Eastern ancestry (Jews or Arabs) and a group of Ecuadorian conversos. (Conversos are Jews who converted to Christianity in Spain during the Inquisition, some of whom migrated to the New World bringing the defective gene with them.) Subsequently, marriage among close relatives (consanguineous marriages) made the disorder more common among the descendants of this group.)

The male-to-female ratio of Laron syndrome differs among certain groups. For instance, in Israel and Ecuador, more females than males are affected. Outside of these populations, the ratio is reversed and more males are affected.

Symptoms of the following disorders can be similar to those of Laron syndrome. Comparisons may be useful for a differential diagnosis:

Coffin-Siris syndrome is a disorder of unknown cause. It is present at birth and affects both sexes. It is chiefly characterized by feeding problems, frequent respiratory infections, and growth deficiencies. (For more information on this disorder, choose "Coffin-Siris" as your search term in the Rare Disease Database.)

Cockayne syndrome is a progressive disorder which manifests itself during the second year of life. It is characterized by a hypersensitivity to sunlight and growth retardation. (For more information on this disorder, choose "Cockayne" as your search term in the Rare Disease Database.)

There are many disorders that can cause dwarfism. For more information on those disorders choose "Dwarf" as your search term in the Rare Disease Database or contact the Human Growth Foundation or the Short Stature Foundation noted in the resources section of this report.

The U.S. Food and Drug Administration (FDA) in August 2005 approved an orphan drug known as Increlex for children whose growth failure is linked to abnormally low levels of insulin-like growth factor type I (IGF-1). Increlex is recombinant IGF-1. It is manufactured by Tercica Inc. Questions about Increlex should be directed to the manufacturer:

Tercica Inc.
2000 Sierra Point Parkway, Suite 400
Brisbane, CA 94005
Phone: (650) 624-2900
Fax: (650) 624-4940
www.tercica.com

Treatment of Laron syndrome with human growth hormone (HGH) is not effective because the body cannot utilize the hormone to grow. If the patient has low blood sugar (hypoglycemia), this condition must be treated to prevent further complications. Other treatment is symptomatic and supportive. Genetic counseling may be of benefit for patients and their families.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Pituitary Dwarfism II. Entry Number; 262500: Last Edit Date; 7/24/1998.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Laron Syndrome, Type II. Entry Number; 245590: Last Edit Date; 6/5/2001.

TEXTBOOKS
DiGeorge AM, Parks JS. Hypopituitarism. In: Behrman RE, Kliegman RM, Arvin AM. Eds. Nelson Textbook of Pediatrics. 15th ed. W.B. Saunder Company. Philadelphia, PA; 1996:1570-71.

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2380.

REVIEW ARTICLES
Baumann G. Genetic characterization of growth hormone deficiency and resistance: implications for treatment with recombinant growth hormone. Am J Pharmacogenomics. 2002;2:93-111.

Laron Z. Clinical Use of somatomedin-1: yes or no? Paediatr Drugs. 1999;1:155-59.

Hull KL, Harvey S. Growth hormone resistance: chemical states and animal models. J Endocrinol. 1999;163:155-72.

JOURNAL ARTICLES
Laron Z. Consequences of not treating children with laron syndrome (primary growth hormone insensitivity). J Paediatr Endocrinol Metab. 2001;14 Suppl 5:1243-48,1261-62.

Kornreich L, Horev G, Schwarz AM, et al. Laron syndrome abnormalities: spinal stenosis, os odontoideum, degenerative changes in atlanto-odontoid joint, and small oropharynx. AJNR Am J Neuroradiol. 2002;23:625-31.

Kaji H. [Laron syndrome by loss of functions of growth hormone receptor] Nippon Rinsho. 2002;60:105-19. [Abstract only].

Takeda K, Sugiura T. [Molecular defects in hormone receptors and G proteins in human disorders Rinsho Byori. 2000;48:396-408. [Abstract only].

Baumbach L, Schiavi A, Bartlett R, et al. Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron’s Syndrome). J Clin Endocr Metab. 1997;82:444-51.

Guevara-Aguirre J, Rosenbloom AL, Vasconez O, et al. Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency. J Clin Endocr Metab. 1997;82:629-33.

FROM THE INTERNET
Wetterau L, Cohen P. Laron Syndrome. eMedicine. Last Updated: September 27, 2002. 13pp.
www.emedicine.com/ped/topic1277.htm

Mosely CT, Phillips JP III, Pituitary Gene Mutations and the Growth Hormone Pathway. Medscape. 2000.
www.medscape.com/viewarticle/410889

Levy RA. Growth Hormone Deficiency (Children). The Magic Foundation. nd. 2pp.
www.magicfoundation.org/divisions/ghd_ch.htm

Lynn JA. Somatotrophin (Growth Hormone) Deficiency. EndocrineSurgeon. nd. 2pp.
www.endocrinesurgeon.co.uk/pituitary/pituitary3-7.html

Dwarfism: Definition. Medcyclopaedia. nd. 1p.
www.amershamhealth.com/medcyclopaedia/Volume%20VII/dwarfism.asp

Dwarfism: Some causes of short stature. Medcyclopaedia. nd. 2pp
www.amershamhealth.com/medcyclopaedia/Volume%20III%201/dwarfism.asp