Laron syndrome

Laron syndrome (Laron syndrome)

1) Disease description (causes and symptoms)

• Cause
  • Pathogenic variants in the growth hormone receptor (GHR) gene (usually inherited in an autosomal recessive manner) cause growth hormone (GH) levels to be normal or elevated, but GH cannot act because of receptor deficiency, resulting in reduced IGF-1 production.
  • Blood levels of GH-binding protein (GHBP), IGF-1, and IGFBP-3 are low.
• Summary of pathophysiology
  • The normal mechanism by which GH stimulates the liver and peripheral tissues to produce IGF-1 is impaired, resulting in low IGF-1 levels and consequently reduced bone lengthening and overall growth.
• Main symptoms
  • Usually normal at birth, but severe growth delay develops from 6–12 months of age, leading to extreme short stature (dwarfism) during childhood
  • Typical facial features: prominent forehead, low nasal bridge, and microcephaly
  • Short limbs (not usually asymmetric, but short in proportion to the trunk), and a small penis and testes (in boys)
  • Normal or mildly reduced intelligence; sexual function and reproductive capacity are usually preserved
  • Metabolic features: tendency toward obesity, osteopenia (reduced bone density), hyperlipidemia, etc.
• Additional clinical findings (findings helpful for diagnosis)
  • Blood GH levels are normal or high, while IGF-1 and IGFBP-3 levels are low
  • In an IGF-1 generation test, there is no or reduced IGF-1 response after GH administration
  • Reported average final adult height: approximately 119 cm for women and 124 cm for men (with substantial individual variation)

2) Treatment methods and precautions

• Standard treatment
  • Subcutaneous administration of recombinant insulin-like growth factor (IGF-1, such as mecasermin) is the mainstay of treatment. (Administration of recombinant GH is ineffective.)
  • The earlier treatment is started, the better the expected final growth outcome.
• Medications/procedures
  • Mecasermin (brand name: Increlex, etc.) — administration should be coordinated with meals to prevent hypoglycemia; regular growth and metabolic monitoring is necessary
• Lifestyle management
  • Weight management (prevention and correction of obesity), a balanced diet, and regular exercise are recommended
  • Calcium and vitamin D intake and bone health monitoring (bone density testing) are recommended in preparation for osteopenia
  • If lipid abnormalities or obesity are present, cardiovascular risk factors should be managed (diet, exercise, and medication if necessary)
• Precautions (treatment-related)
  • Common complications of IGF-1 treatment: hypoglycemia (especially immediately after administration), injection-site reactions, and increased frequency of nasopharyngeal and middle-ear infections, etc.
  • Rarely, intracranial hypertension (benign increased intracranial pressure) has been reported → immediate evaluation is necessary if headache or visual disturbances occur
  • Regular monitoring of growth (height, growth velocity, and bone age), blood IGF-1 levels, and metabolic panels (blood glucose and lipids)
• Risk of complications
  • If untreated or inadequately monitored, the risk of metabolic complications such as obesity, osteopenia, and hyperlipidemia increases
  • In general, cancer incidence tends to be low according to available reports, but this is related to epidemiological characteristics and requires further validation

3) Checkpoints before an outpatient visit (items to prepare and information to confirm)

• Items/documents to prepare
  • A list of recently used medications (including supplements) and administration times
  • Previous growth charts (for children, records from public health centers, vaccination booklets, etc.) and parents’ heights (family history)
  • Previous test results: blood GH, IGF-1, IGFBP-3, genetic test results (if available), bone age and bone density tests, and blood tests (lipids and fasting blood glucose)
  • A record of symptom changes (when growth delay was first noticed, weight changes, headache or visual changes, etc.)
  • A brief note on sleep, eating, and activity patterns
• Information to tell the healthcare provider first during the outpatient visit
  • Any recent fever or infection, vaccination, or start of another treatment
  • Any history of hypoglycemia symptoms (lethargy, cold sweats, trembling, etc.)

Example questions (for patients/guardians to review themselves)

• Changes in height and weight over the past 3–6 months (values or increasing/decreasing trends)
• Any recent changes in appetite, sleep, or activity level
• Medication administration times and method of administration (especially if insulin-like growth factor administration is planned)

4) Examples of general questions to ask the doctor

• "What are the expected effects and side effects of this treatment (IGF-1)?"
• "When should treatment be started, what is the expected treatment duration, and what are the treatment goals (growth velocity and target IGF-1 level)?"
• "Which tests are needed during treatment, and how often should they be performed?"
• "What points require particular attention regarding lifestyle habits (diet and exercise)?"
• "How likely are complications (bone loss and metabolic abnormalities), and how can they be prevented?"

5) Examples of disease-specific questions (1–2)

• "Is genetic counseling for our (or my child’s) genetic test results and related family inheritance (recurrence risk, recommendations for testing siblings, etc.) necessary?"
• "If IGF-1 treatment is started, what degree of improvement in expected final height can be anticipated? Could you explain specifically about the timing of treatment (for example, why it should be started as early as possible)?"

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Note: Diagnosis and treatment vary according to each patient’s individual circumstances (age, growth velocity, coexisting conditions, genetic test results, etc.). Please consult the treating specialist to determine the actual testing and treatment plan.