From the Guidelines
Laron syndrome patients should be treated with recombinant insulin-like growth factor-1 (IGF-1) therapy, such as mecasermin (Increlex), to improve growth outcomes and quality of life, while also potentially reducing the risk of aging-related diseases like cancer and diabetes, as evidenced by their naturally reduced insulin/IGF-1 signaling pathway activity 1.
Key Characteristics of Laron Syndrome
- Severe short stature
- Delayed bone age
- Characteristic facial features, including prominent forehead and underdeveloped nasal bridge
- Obesity
- Delayed puberty
- Hypoglycemia ### Treatment and Management
- Recombinant IGF-1 therapy, typically administered as mecasermin (Increlex) at doses of 40-120 μg/kg twice daily by subcutaneous injection
- Treatment should begin as early as possible for optimal height outcomes and continue through puberty
- Regular monitoring of IGF-1 levels, growth velocity, and potential side effects like hypoglycemia is essential ### Reduced Risk of Aging-Related Diseases
- Individuals with Laron syndrome have significantly reduced rates of cancer and diabetes due to their reduced insulin/IGF-1 signaling pathway activity 1
- This reduced pathway activity may increase lifespan and postpone the advent of aging-related diseases, as supported by research on the insulin/insulin-like growth factor signaling pathway and the mammalian or mechanistic target of rapamycin (mTOR) pathway 1
From the Research
Definition and Characteristics of Laron Syndrome
- Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner 2.
- The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect 2.
- Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration 2, 3.
- Typical appearance includes dwarfism, facial phenotype, obesity, and hypogenitalism 2, 3.
Clinical Features and Treatment
- LS patients suffer from hypoglycemia, hypercholesterolemia, and sleep disorders, but surprisingly have a very low cancer risk 2.
- The treatment of LS is recombinant IGF-1, which stimulates linear growth but increases the degree of obesity 3.
- Adult-age patients with congenital IGF-1 deficiency are protected from cancer but can develop insulin resistance, glucose intolerance, diabetes, and cardiovascular disease 3.
- IGF-1 treatment can also lead to hyperandrogenism in female patients, characterized by oligo/amenorrhoea and acne 4.
Epidemiology and Prognosis
- Globally, around 350 people are affected by this syndrome, with two large groups living in separate geographic regions: Israel and Ecuador 2.
- Laron syndrome was first described by the Israeli physician Zvi Laron in 1966 2.
- Treatment with recombinant IGF1 has improved the prognosis in these patients, but does not actually realize the conditions for genuine replacement therapy 5.
- LS is a unique disease model presenting a dissociation between GH and IGF-1 activity, offering a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment 2, 3.