Laron syndrome

Other Names: Growth hormone insensitivity syndrome; Pituitary dwarfism II; Growth hormone receptor deficiency; Primary growth hormone resistance; Primary growth hormone insensitivity; Laron dwarfism; Laron type pituitary dwarfism Laron syndrome is a condition that occurs when the body is unable to utilize growth hormone. It is primarily characterized by short stature.

Growth hormone, a substance produced by the brain's pituitary gland that helps promote growth. Affected individuals are close to normal size at birth, but they experience slow growth from early childhood that results in very short stature.

Cause

Laron syndrome is caused by changes (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 which causes the many signs and symptoms of Laron syndrome.

Inheritance

Autosomal recessive inheritance, a 25% chance

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.

Signs and symptoms

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)

People affected by Laron syndrome appear to have a reduced risk of cancer and type 2 diabetes.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Aplasia/Hypoplasia involving the nose(Decreased nasal size)
• Delayed eruption of teeth(Delayed eruption)
• Delayed skeletal maturation(Delayed bone maturation)
• High forehead
• Hypoplastic nasal bridge(Decreased size of nasal bridge)
• Microdontia(Decreased width of tooth)
• Micrognathia(Little lower jaw)
• Reduced number of teeth(Decreased tooth count)
• Severe short stature(Dwarfism)
• Truncal obesity

30%-79% of people have these symptoms

• Abnormality of the elbow(Abnormality of the elbows)
• Brachydactyly(Short fingers or toes)
• Delayed puberty(Delayed pubertal development)
• Hypoglycemia(Low blood sugar)
• Hypoplasia of penis(Underdeveloped penis)
• Motor delay
• Short toe(Short toes)
• Underdeveloped supraorbital ridges(Flattened bony protrusion above eyes)

5%-29% of people have these symptoms

• Blue sclerae(Whites of eyes are a bluish-gray color)
• Depressed nasal ridge(Flat nose)
• High pitched voice
• Hypercholesterolemia(Elevated serum cholesterol)
• Hypohidrosis(Decreased ability to sweat)
• Intellectual disability(Mental deficiency)
• Osteoarthritis(Degenerative joint disease)
• Prematurely aged appearance(Precociously senile appearance)

Diagnosis

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 and reduced levels of insulin-like growth factor I. Genetic testing for changes (mutations) in the GHR gene can also be used to confirm a diagnosis in some cases.

Treatment

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. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition

• Mecasermin (Brand name: Increlex®) 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 (Brand name: Iplex®)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.

Prognosis

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. This template is no longer used; please see Template:Endocrine pathology for a suitable replacement

NIH genetic and rare disease info

• NIH info on Laron syndrome

Laron syndrome is a rare disease.

Laron syndrome Resources
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