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Laron syndrome

Laron syndrome is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Laron syndrome rather than just read about it. In short: Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin-C) production in response to growth hormone (GH; hGH; somatotropin). It is usually caused by inherited growth hormone receptor (GHR) mutations.

Laron syndrome — main illustration
Laron syndrome — illustration

Key takeaways

  • Laron syndrome belongs to biology; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Laron syndrome to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Laron syndrome from memory before moving on to harder problems.

Reference excerpt

Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin-C) production in response to growth hormone (GH; hGH; somatotropin). It is usually caused by inherited growth hormone receptor (GHR) mutations. The syndrome is named after the scientist Zvi Laron who first discovered the syndrome in 1966. Affected individuals classically present with short stature between −4 and −10 standard deviations below median height, obesity, craniofacial abnormalities, micropenis, low blood sugar, and low serum IGF-1 despite elevated basal serum GH. LS is a very rare condition with a total of 250 known individuals worldwide. The genetic origins of these individuals have been traced back to Mediterranean, South Asian, and Semitic ancestors, with the latter group comprising the majority of cases. Molecular genetic testing for growth hormone receptor gene mutations confirms the diagnosis of LS, but clinical evaluation may include laboratory analysis of basal GH, IGF-1 and IGFBP levels, GH stimulation testing, and/or GH trial therapy. People with LS are unresponsive to growth hormone therapy; the disease is instead treated mainly with recombinant IGF-1, Mecasermin. Evidence has suggested that people with Laron syndrome have a reduced risk of developing cancer and diabetes mellitus type II, with a significantly reduced incidence and delayed age of onset of these diseases compared to their unaffected relatives. The molecular mechanisms of increased longevity and protection from age-related disease among people with LS is an area of active investigation.

Presentation

Physical features LS is recognized as being part of a spectrum of conditions that affect the Hypothalamic–pituitary–somatotropic axis and cause significant derangements in human growth, development, and metabolism. Along this spectrum of conditions, individuals with LS and growth hormone deficiency display short stature, while individuals with acromegaly and gigantism result in the opposite phenotype of tall stature. In addition to short stature, other characteristic physical symptoms of LS include: prominent forehead, depressed nasal bridge, underdevelopment of mandible, truncal obesity, and micropenis in males. Left untreated, the average height attained by individuals with LS are approximately 4–4.5 feet (1.2–1.4 m) in women/men respectively. Additional physical features include delayed bone age, hypogonadism, blue sclera, high-pitched voice, acrohypoplasia, sparse hair growth, and crowded teeth. The breasts of females reach normal size, and in some are large in relation to body size. It has been suggested that hyperprolactinemia may contribute to the enlarged breast size. Seizures are frequently seen secondary to hypoglycemia. Some genetic variations decrease intellectual capacity. Laron syndrome patients also do not develop acne, except temporarily during treatment with IGF-1 (if performed).

Pathophysiology

Under normal circumstances in humans, growth hormone (GH) is released in a pulsatile fashion from cells known as somatotrophs in the anterior pituitary gland. These pulses of GH are regulated by cells in the hypothalamus, via the release of growth hormone-releasing hormone (GHRH) into the hypothalamohypophysial system when stimulated by insulin, ghrelin, glucagon, arginine, deep sleep, exercise, fasting, sex hormone release during puberty, and a host of other factors. GH release is inhibited by somatostatin (GHIH), IGF-1, hyperglycemia, and glucocorticoids. Once released, the GH molecules travel through the bloodstream and eventually bind to GH receptors on the surface of cells composing bodily organs and tissues. One major site of action for GH is in the liver, where it stimulates gluconeogenesis and the release of IGF-1 through the JAK-STAT signaling pathway. IGF-1 promotes growth in a variety of tissues throughout the body, especially bone mineralization, and provides negative feedback on GH release. GH results in increased muscle mass, lipolysis, and protein synthesis. Obesity and increased adipose tissue, especially visceral fat, results in reduced GH secretion. There is a natural age-related decline in the GHRH-stimulated release of GH.

Growth hormone receptor mutations Molecular genetic investigations have shown that LS is mainly associated with autosomal recessive mutations in the gene for the growth hormone receptor (GHR). These can result in defective hormone binding to the ectodomain or reduced efficiency of dimerization of the receptor after hormone occupancy. LS is generally classified as "primary" GH insensitivity, which is distinguished from "secondary" GH insensitivity. Primary (congenital/hereditary) GH insensitivity may result from growth hormone receptor defects, as in the case of Laron syndrome, but can also be caused by defective post-receptor signal transduction (STAT5B), abnormalities of the IGF-1 gene or IGF-1 receptor. Secondary (acquired) GH insensitivity results from antibodies to growth hormone or the growth hormone receptor, as well as poor nutritional status, liver disease or diabetes mellitus. A GHR mutation that results in only partial insensitivity to GH can manifest as a form of idiopathic short stature.

STAT5B A related condition involving postreceptor insensitivity to growth hormone has been associated with STAT5B.

Diagnosis LS should be suspected in children or adults with distinctive physical features listed above, extremely elevated serum hGH concentrations despite low serum IGF-1 levels. A failure of IGF-1 to increase in response to exogenous hGH (IGF-1 stimulation test) is diagnostic for LS. The gold standard for confirming a diagnosis of LS is to perform a genetic analysis with PCR to identify the precise molecular defect in the GH receptor gene. Other laboratory abnormalities include GHBP (growth hormone binding protein) levels being low in cases with mutations in the extracellular domain of the GH receptor and normal in cases with mutations in the intracellular domain. Low serum levels of IGFBP are non-diagnostic for LS.

… excerpt ends here. Continue reading the full article.

Illustrations

Laron syndrome illustration
Laron syndrome: Laron syndrome has an autosomal recessive pattern of inheritance.
Laron syndrome has an autosomal recessive pattern of inheritance.
Laron syndrome illustration
Laron syndrome: Impact of insulin/IGF-1 signaling in Laron syndrome (A) and Western diet (B) on FoxO-mediated gene regulation and associated pathologies. GHR*, growth hormone receptor loss of function mutation in Laron syndrome; GIP, glucose-dependent insulinotropic polypeptide, a whey protein-induced incretin, which stimulates β-cell proliferation and insulin secretion; PRL, prolactin; PRL secretion is induced by serotonergic hypothalamic signaling; Trp, tryptophan, and Leu, leucine, essential amino acids enriched in the whey protein α-lactalbumin; Trp via serotonin synthesis stimulates pituitary GH and PRL secretion and Leu stimulates β-cell proliferation and insulin secretion.
Impact of insulin/IGF-1 signaling in Laron syndrome (A) and Western diet (B) on FoxO-mediated gene regulation and associated pathologies. GHR*, growth hormone receptor loss of function mutation in Laron syndrome; GIP, glucose-dependent insulinotropic polypeptide, a whey protein-induced incretin, which stimulates β-cell proliferation and insulin secretion; PRL, prolactin; PRL secretion is induced by serotonergic hypothalamic signaling; Trp, tryptophan, and Leu, leucine, essential amino acids enriched in the whey protein α-lactalbumin; Trp via serotonin synthesis stimulates pituitary GH and PRL secretion and Leu stimulates β-cell proliferation and insulin secretion.

Worked examples

Example 1 — a first encounter with Laron syndrome

Start with the simplest possible case. Write down what Laron syndrome claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Laron syndrome before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Laron syndrome ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Laron syndrome

In research
Laron syndrome appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Laron syndrome in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Laron syndrome is common in secondary-school and first-year university syllabi. It links to neighbouring topics Autosomal recessive disorders, Cell surface receptor deficiencies, Disorders causing seizures, so understanding it makes those chapters shorter.
In everyday life
Look for Laron syndrome outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.
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How to study Laron syndrome in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Laron syndrome means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Laron syndrome out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Laron syndrome in simple terms?

Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin-C) production in response to growth hormone (GH; hGH; somatotropin). It is usu…

Why does Laron syndrome matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Laron syndrome?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Laron syndrome.

Tags

  • Autosomal recessive disorders
  • Cell surface receptor deficiencies
  • Disorders causing seizures
  • Growth disorders
  • Growth hormones
  • Rare syndromes
  • Syndromes affecting stature

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