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At a glance

It is a genetically transmitted endocrine disorder characterized by severe dwarfism. It is associated with a congenital insensitivity to growth hormone (GH). Besides dwarfism, the clinical features include a blue sclerae, hip degeneration, prominent forehead, depressed nasal bridge, micrognathia, truncal obesity, and micropenis. Females have normal sexual character development. Acute hypoglycemia and seizures are often present. As a matter of interest, it was reported in 2011 that individuals affected with this medical condition in Ecuador are resistant to cancer, diabetes mellitus, and to an extent protected against aging.

Synonyms

Growth Hormone Insensitivity Syndrome; Laron Dwarfism (or Laron-Type Dwarfism); Primary GH Insensitivity (Primary GH Resistance); Pituitary Dwarfism II.

History

It is a genetic disorder that was first reported by Laron et al in 1966. Most patients are of Jewish descent (including many individuals who converted to Christianity during the Spanish Inquisition and emigrated to the New World).

Incidence

More than 250 cases have been reported worldwide. Male-to-female ratio varies based on geographic area.

Genetic inheritance

Autosomal recessive; gene locus at 5p13.1-p12 (33 mutations have been reported).

Pathophysiology

Mutation of the gene encoding the GH receptor (Type I dwarfism) or a defect in the postreceptor signaling mechanism (Type II dwarfism), resulting in complete resistance to the action of GH and failure to generate somatomedin or insulin-like growth factor-1 (IGF-1). Lack of feedback causes pituitary oversecretion of GH.

Diagnosis

Clinical signs of GH deficiency including biochemical (normal or increased plasma GH levels, low IGF-1 levels unresponsive to exogenous GH, and low GH-binding protein levels) and radiologic (delayed bone age, markedly advanced osseous maturation for height and age).

Clinical aspects

Clinical hyposomatotropism manifested by proportionate short stature, delayed bone age, limited elbow extension, and hip degeneration. An important characteristic is the more pronounced decrement in body size than in head size, resulting in childlike body proportions in adults, small face, prominent forehead occasionally blue sclerae, flat nasal bridge, and delayed tooth development. Patient may have micrognathia, sparse hair, high-pitched voice (caused by a narrow larynx), delayed menarche in girls, a small-size penis (which reaches normal adult size) in boys, and normal intelligence. Adult stature is severely affected (ranging from −4 to −12 standard deviation). Approximately 50% of infants and children affected with Laron Syndrome present overt symptoms of hypoglycemia (especially fasting hypoglycemia) causing seizures. Hip dysplasia, especially avascular necrosis of the femoral head (Legg-Calvé-Perthes disease) is common in this medical condition.

Precautions before anesthesia

Because of increased risk for spinal cord compression and atlantoaxial odontoid subluxation, all patients must be assessed very carefully prior to anesthesia (eg, clinically and ...

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