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