Introduction
Laron syndrome, also known as Laron-type dwarfism, is a rare genetic disorder in which there is a deficit of response to growth hormones. People with Laron syndrome have short stature and other physical features, caused by mutations in the growth hormone receptor gene. Patient organizations create public awareness about the disease and enable patients and families to connect with each other. In-person and online resources are provided by these organizations to enable people with Laron syndrome to cope with the disease condition. Many collaborate with researchers and other medical professionals and extend help to those affected by this condition.
What Is Laron Syndrome?
Laron syndrome, also known as growth hormone sensitivity syndrome, is an uncommon disorder characterized by the body's inability to effectively utilize growth hormones. The typical characteristic of Laron syndrome is dwarfism or short stature. The pituitary gland, located in the brain, produces a chemical substance called growth hormone, which plays a crucial role in facilitating growth and development. People affected with Laron syndrome are of normal size at birth, but they show delayed growth from childhood resulting in short stature. If the condition is left untreated for long, males attain a maximum height of 4.5 feet, and females reach a height of four feet.
What Is the Prevalence of Laron Syndrome?
Laron syndrome or Laron dwarfism is a rare disorder. Only 350 people in the world have been diagnosed with this condition. The largest group of people who were diagnosed with this condition live in Southern Ecuador. However, studies have suggested that people diagnosed with Laron syndrome are less likely to acquire cancer and type 2 diabetes. In addition, despite obesity, people with Laron syndrome are less likely to develop other diseases. However, the lifespan of these individuals is less than that of unaffected individuals.
What Are the Causes of Laron Syndrome?
Laron syndrome is a genetic disorder caused by mutations or defects in the growth hormone receptor (GHR) gene. This gene contains information and instructions for synthesizing a protein known as the growth hormone receptor. Usually, this receptor is present on the outer membrane of the liver cells. As the name suggests, the growth hormone receptor binds to the growth hormone, and the two fit together like a lock and key.
When the growth hormone binds to its receptors, it stimulates cell growth and division. The production of insulin-like growth factors (IGF-1) from the liver cells is also stimulated by the growth hormone. Growth hormone and IGF-1 have several effects on the growth and function of the different parts of the body. The problem arises due to variations or mutations in the GHR. These mutations impair the abilities of the receptors to bind with the growth hormone or trigger signaling of the cells.
As a result, the cells cannot respond even if the growth hormone is available. This inability of the cells to respond to the growth hormone is known as growth hormone insensitivity. As a result of this insensitivity, the growth and functions of many areas of the body get disrupted. However, the mechanism by which mutations in the GHR gene occur is still a topic of research. Growth hormone insensitivity also alters the mechanism of action of insulin. As a result, people with Laron syndrome have increased insulin sensitivity and are less likely to develop diabetes.
What Are the Signs and Symptoms of Laron Dwarfism?
The signs and symptoms of Laron syndrome vary from person to person. Laron syndrome symptoms that are commonly seen include the following:
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Truncal obesity (accumulation of fats around the abdomen).
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Tooth agenesis (absence of one or more teeth or the failure of tooth development).
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Short stature.
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Micrognathia (a condition in which the lower jaw is small in size).
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Microdontia (decreased size of the tooth).
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Hypoplastic or small nasal bridge.
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Increased height of the forehead.
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Delayed rate of skeletal maturation.
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Underdevelopment or absence of the nose or its parts.
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Endocrine system abnormalities.
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Abnormal morphology of the face.
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Underdeveloped eyebrows.
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Short or stubby toes.
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Delayed motor development.
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Underdeveloped penis.
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Delayed pubertal growth.
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The fingers or toes appear short.
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Abnormality in the elbow joints.
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The patient appears aged.
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Degeneration or wear of the articular cartilage.
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Poor intellect.
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Excessive sweating.
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High-pitched voice.
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Bluish discoloration of the sclera.
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Abnormal morphology of the skull bones.
What Is the Inheritance Pattern of Laron Syndrome?
Laron syndrome is inherited in an autosomal recessive pattern meaning both copies of the GHR gene are mutated or defective. The parents of the individual having an autosomal recessive condition carry one copy of the defective gene. However, they do not present with any signs and symptoms of the disease.
How Is Laron Syndrome Diagnosed?
Laron syndrome diagnosis begins with a thorough medical history of the patient’s condition. The diagnostic procedures are described below:
Medical History - A medical history is verbal communication between the doctor and the patient. It helps the doctor recognize the patient’s illness and gives him a general idea about his medical condition.
Physical Examination - The physical examination allows the doctor to check the physical signs of Laron dwarfism. For example, a patient suffering from Laron dwarfism appears small in height and has a characteristic facial appearance.
Laboratory Tests - Laboratory tests are done to check a sample of the patient’s blood, urine, and body tissues to diagnose diseases. Patients suffering from Laron syndrome usually present with hypoglycemia (low blood glucose levels) and hypercholesterolemia (elevated blood cholesterol levels).
Genetic Analysis With Polymerase Chain Reaction (PCR) - It is the gold standard for diagnosing Laron syndrome. A sample of the patient’s tissues will be taken and tested in the laboratory to detect any mutations in the GHR gene.
How Is Laron Syndrome Managed?
Currently, there are no medications or treatment plans available for Laron syndrome. However, the treatment aims to improve the growth of the affected individual. The only treatment option available to manage Laron syndrome is subcutaneous injections of IGF-1. This is because IGF-1 stimulates brain growth, height, and metabolic abnormalities produced by IGF-1 deficiency. It also helps increase blood glucose levels, lower cholesterol, and increase muscle strength. Therefore, IGF-1 and growth hormone levels must be carefully monitored in patients undergoing the treatment. The following medications help manage Laron syndrome:
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Mecasermin - This medication helps in the long-term treatment of growth failure in children suffering from severe deficiency of IGF-1 or the deletion of the growth hormone genes.
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Mecasermin Rinfabate - It is used to treat growth failure in children with IGF-1 or growth hormone deficiency.
Conclusion:
Laron syndrome is a rare genetic condition that mainly affects children. The typical facial and bodily appearance of the patient makes it easier for the doctors to diagnose this condition. Predicting the prognosis of the disease is challenging, as only a limited number of individuals have been diagnosed with this condition. In addition, there is no specific cure for this disease, but certain drugs are available to help overcome the symptoms of this condition and improve growth hormone levels. So, individuals diagnosed with Laron syndrome need not worry and can consult their doctor at the earliest to know more about its treatment.
