Laron Syndrome

Genetically transmitted endocrine disorder characterized by congenital insensitivity to growth hormone (GH). It is characterized by short stature, blue sclerae, hip degeneration, and delayed bone age.

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

Genetic disorder 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).

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

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

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.

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 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 child-like 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 with Laron syndrome present with overt symptoms of hypoglycemia (especially fasting hypoglycemia), including seizures. Hip dysplasia, especially avascular necrosis of the femoral head (Legg-Calvé-Perthes disease) is common.

Because of increased risk for spinal cord compression and atlantoaxial odontoid subluxation, all patients must be assessed very carefully prior to anesthesia (e.g., clinically and radiologically). The investigation should include a complete endocrinologic evaluation, including and lung ventilation glucose level and tolerance to fasting. Avoid long periods of fasting.

Intelligence usually is normal for chronologic age. Limited elbow movement and hip degeneration calls for extra care during positioning of the patient. A difficult airway may be encountered in the presence of micrognathia. Manipulate patient's head very cautiously, especially during tracheal intubation (possible cervical spine instability) and positioning for surgery. Check blood glucose intraoperatively and postoperatively.

No known specific pharmacological implications; however, the basic principles of safe airway management in these patients dictate that spontaneous ventilation should be maintained until an easy tracheal intubation and lung ventilation can be confirmed. Therefore, neuromuscular blockade agents must be used judiciously.

Coffin-Siris Syndrome: Present at birth and affects both sexes equally. Characterized by severe failure to thrive, frequent respiratory infections, and growth deficiencies.

Cockayne Syndrome: Progressive disorder presenting with onset during the second year of life and characterized by photosensitivity and growth retardation.

Pituitary Dwarfism: Panhypopituitary dwarfism is not considered a rare condition, considering that approximately 7000 to 10,000 cases have been diagnosed in the United States. Most cases are the result of craniopharyngioma and other nongenetic causes. If inherited, it is believed to be autosomal recessive, but rare.