Unlocking the Mysteries of Laron Syndrome: Genetic Testing for Improved Diagnosis and Management

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Laron syndrome, also known as growth hormone insensitivity syndrome, is a rare genetic disorder characterized by short stature and resistance to the effects of growth hormone. The condition is caused by mutations in the growth hormone receptor gene (GHR), leading to undetectable serum growth hormone-binding protein (GHBP) levels. Genetic testing has emerged as a valuable tool for diagnosing and managing Laron syndrome, offering new insights into the disease and potential treatment options. In this article, we will explore the role of genetic testing in understanding, diagnosing, and using genetic testing for Laron syndrome with undetectable serum GHBP.

Understanding Laron Syndrome

Laron syndrome is a rare autosomal recessive disorder that affects approximately 1 in 1 million people worldwide. The condition is caused by mutations in the GHR gene, which encodes the growth hormone receptor. This receptor is essential for the binding of growth hormone (GH) to its target cells, enabling the hormone to stimulate growth and development. In individuals with Laron syndrome, the GHR gene is mutated, resulting in an impaired or nonfunctional growth hormone receptor. Consequently, the affected individuals are unable to respond to growth hormone, leading to short stature and other clinical features such as delayed bone age, obesity, and hypoglycemia.

Diagnosing Laron Syndrome

Diagnosing Laron syndrome can be challenging, as the clinical features of the condition can overlap with other growth disorders. Traditionally, the diagnosis has relied on clinical examination, biochemical tests, and radiological assessments. However, genetic testing has emerged as a powerful tool for confirming the diagnosis of Laron syndrome and identifying the specific GHR gene mutations responsible for the condition.

GH-binding protein activity and IGF-I measurements

A study by Laron et al. demonstrated that measuring serum GH-binding protein activity and insulin-like growth factor I (IGF-I) levels can help identify heterozygous carriers of Laron syndrome. This approach is valuable for genetic counseling, enabling at-risk families to better understand their risk of having a child with Laron syndrome.

Identification of novel GHR gene mutations

Genetic testing has also led to the discovery of new GHR gene mutations associated with Laron syndrome. For example, a study by Wu et al. identified a novel homozygous substitution mutation (E42K) in the GHR gene in a Chinese girl with Laron syndrome. Similarly, Keskin et al. reported a novel mutation (W104R) at exon 5 of the GHR gene in a patient with Laron type dwarfism. These findings highlight the genetic heterogeneity of Laron syndrome and underscore the importance of genetic testing in accurately diagnosing the condition.

Using Genetic Testing for Laron Syndrome Management

Long-term IGF-I treatment

Genetic testing can also inform the management of Laron syndrome by guiding treatment decisions. A study by Laron et al. evaluated the long-term effects of IGF-I treatment on serum IGF-binding protein-3 and the acid-labile subunit in Laron syndrome patients with normal growth hormone binding protein. The findings suggest that IGF-I treatment can be a viable option for managing Laron syndrome, particularly in patients with specific GHR gene mutations.

Genetic counseling and family planning

Genetic testing for Laron syndrome can also play a crucial role in genetic counseling and family planning. By identifying carriers of GHR gene mutations, at-risk couples can make informed decisions about having children and explore options such as preimplantation genetic diagnosis (PGD) to minimize the risk of having a child with Laron syndrome.

In conclusion, genetic testing has emerged as a valuable tool for understanding, diagnosing, and managing Laron syndrome with undetectable serum GH-binding protein. By identifying the specific GHR gene mutations responsible for the condition and guiding treatment decisions, genetic testing can improve the quality of life for individuals with Laron syndrome and their families.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)