Laron syndrome




Laron syndrome is a condition that occurs when the body is unable to utilize growth hormone. It is primarily characterized by short stature.  It is often caused by mutations in the GHR gene and is inherited in an autosomal recessive manner. Treatment is focused on improving growth and generally includes injections of insulin-like growth factor 1 (IGF-1).

Type 1 involves a defect in the growth hormone receptor gene which prevents the hormone from binding and being used. Hence there are high levels of free growth hormone in the plasma. Type 2 involves a problem with the processing of the growth hormone once it has been bound properly to the cell surface.


 Laron syndrome is a rare condition in which the body is unable to use growth hormone. The primary symptom is short stature.
Although affected people are generally close to average size at birth, they experience slow growth from early childhood. If left untreated, adult males with Laron syndrome typically reach a maximum height of about 4.5 feet and adult females may be just over 4 feet tall.

Other signs and symptoms associated with the condition vary but may include:

  • Reduced muscle strength and endurance
  • Hypoglycemia in infancy
  • Delayed puberty
  • Small genitals
  • Thin, fragile hair
  • Dental abnormalities
  • Short limbs (arms and legs)
  • Obesity
  • Distinctive facial features (protruding forehead, a sunken bridge of the nose, and blue sclerae)


Laron syndrome is caused by mutations in the GHR gene. This gene encodes growth hormone receptor, which is a protein found on the outer membrane of cells throughout the body. Growth hormone receptor is designed to recognize and bind growth hormone, which triggers cellular growth and division. When growth hormone is bound to the growth hormone receptors on liver cells, specifically, insulin-like growth factor I (another important growth-promoting hormone) is produced. Mutations in GHR impair the function of growth hormone receptors which interferes with their ability to bind growth hormone. This disrupts normal growth and development of cells and prevents the production of insulin-like growth factor I (IGF-1) which causes the many signs and symptoms of Laron syndrome.


Genetical counselling is recommended. Most cases of Laron syndrome are inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Reports exist of rare families in which Laron syndrome appears to be inherited in an autosomal dominant manner. In these cases, a person only needs a change in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. An affected person has a 50% chance with each pregnancy of passing along the altered gene to his or her child


A diagnosis of Laron syndrome is often suspected based on the presence of characteristic signs and symptoms. Additional testing can then be ordered to confirm the diagnosis and rule out other conditions that cause similar features. This generally includes blood tests to measure the levels of certain hormones that are often abnormal in people with Laron syndrome. For example, affected people may have:

  • Elevated levels of growth hormone (GH)
  • Reduced levels of insulin-like growth factor I (IGF-1)
  • Genetic testing for changes in the GHR gene can also be used to confirm a diagnosis in some cases


The long-term outlook (prognosis) for people with Laron syndrome is generally good. The condition does not appear to affect lifespan and is associated with a reduced risk of cancer and type 2 diabetes.


There is currently no cure for Laron syndrome. Treatment is primarily focused on improving growth. The only specific treatment available for this condition is subcutaneous injections of insulin-like growth factor 1 (a growth-promoting hormone), often called IGF-1. IGF-1 stimulates linear growth (height) and also improves brain growth and metabolic abnormalities caused by long-term IGF-1 deficiency. It has also been shown to raise blood glucose levels, reduce cholesterol, and increase muscle growth. IGF-1 and GH levels should be closely monitored in people undergoing this treatment because overdosage of IGF-I causes a variety of health problems.

Approved therapies:

  • Mecasermin (Increlex) FDA-approved indication: Long-term treatment of growth failure in children with severe primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to growth hormone.  
  • Mecasermin rinfabate (Iplex) FDA-approved indication: Treatment of growth failure in children with severe primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to growth hormone


Refer to Research Publications.