Genetic disease that causes the triad of optic nerve
hypoplasia, structural brain abnormalities, and hypothalamic/pituitary
Septo-Optic Dysplasia; Optic Nerve Hypoplasia;
Some cases are sporadic, whereas other cases
seem to indicate autosomal dominant and recessive patterns of inheritance.
Caused by mutation in the homeobox gene HESX1. The
typical picture includes optic hypoplasia, pituitary hypofunction, and
midline defects of the prosencephalon. Milder forms exist in individuals
with heterozygous mutations of the gene.
Clinical picture, family history, brain imaging, and
cytogenetic identification of mutations of the HESX1 gene.
Wide variability in the clinical picture. The
syndrome is characterized by hypoplasia of the optic disk and nerve,
hypothalamic-pituitary axis defects, and agenesis of the septum pellucidum.
Agenesis of the corpus callosum, hypoplastic cerebellar changes similar to
Dandy-Walker malformation, hemiparesis or hemiplegia, spasticity, and mental
retardation (mild-to-severe) have been described as optional signs. The
extent of pituitary involvement ranges from growth hormone deficiency only
to panhypopituitarism. The clinical picture of decreased hormone levels may
result not only in short stature but also in hypoglycemia (decreased levels
of adrenocorticotropic hormone), diabetes insipidus, and precocious puberty.
Visual impairment is usually noted at birth, ranging from decreased vision
in one eye to no vision in both eyes secondary to optic disc atrophy and
corneal opacification. Variable pupillary dilatation and searching nystagmus
can often be found. Facial features include a flat face and midline cleft
lip. Abnormal external genitalia (cryptorchidism, micropenis) have been
reported. Patients are prone to intercurrent infections.
The hazards of anesthetizing a
patient in whom the syndrome has not been recognized have been documented.
Bear the diagnosis in mind in a patient with visual impairment and small
stature. Ideally, the patient is under the care of an endocrinologist. Ask
about episodes of hypoglycemia. The patient may be on chronic hormone
replacement therapy, requiring additional hydrocortisone stress coverage in
the perioperative period. Preoperative assessment should include evaluation
of hydration and electrolytes in view of possible diabetes insipidus. Check
Sudden unexpected death has been
described in these patients, probably as a consequence of intercurrent viral
illness and consecutive adrenal crisis. Specific attention must be
paid to prevent hypoglycemia. Maintaining hydration, if diabetes insipidus is
present, is crucial, and extra doses of hydrocortisone to cover for
perioperative stress are required. Temperature control is important because
patients may suffer from thermoregulatory disturbances.
Be aware of interactions between
anticonvulsants and anesthetic drugs. Hormone replacement therapy must be
Brodsky MC, Conte FA, Taylor D, et al: Sudden death in septo-optic
dysplasia: Report of 5 cases. Arch Ophthalmol
Sherlock DA, McNicol LR: Anaesthesia and septo-optic dysplasia. Implications
of missed diagnosis in the peri-operative period. Anaesthesia
Thomas PQ, Dattani MT, Brickman JM, et al: Heterozygous HESX1 mutations
associated with ...