Laron Syndrome: Genetic Growth Hormone Insensitivity and Emerging Clinical Insights
Overview of the Disorder Laron Syndrome is a rare inherited condition characterized by the body’s inability to respond properly to growth hormone due to mutations in the growth hormone receptor (GHR) gene. Although circulating growth hormone levels may be normal or elevated, defective receptor signaling prevents downstream production of insulin-like growth factor 1 (IGF-1), leading to impaired growth and distinctive physical traits. First identified in the 1960s, this disorder has become an important model for understanding endocrine signaling and growth regulation in humans. Genetic Basis and Disease Mechanism The disorder arises from loss-of-function mutations in the GHR gene located on chromosome 5. These mutations interfere with receptor activation, dimerization, or intracellular signaling through pathways such as JAK2-STAT5. Inheritance follows an autosomal recessive pattern, meaning both copies of the gene must be affected for the condition to manifest clinically. Carriers...
