Septo-Optic Dysplasia

Synonyms: De Morsier syndrome, pituitary hormone deficiency combined HESX1-related, septo-optic dysplasia, SOD

Septo-optic dysplasia is a rare, heterogeneous condition characterised by a combination of pituitary gland hypoplasia, optic nerve hypoplasia and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum.¹

This is a rare condition, in the order of less than 10 per 100,000 of the population. A study from Greater Manchester and Lancashire has identified cases being more common where there is high unemployment, low income and in teenage pregnancies,² this association with young mothers having been previously been reported in Glasgow.³

Genetics of SOD

The condition is caused by mutation of the gene locus 3p21.2-p21.1 that controls HESX1, an important regulator of development - particularly of the pituitary. Although it appears to be genetic in origin it rarely runs in families, suggesting that mutation is more often spontaneous than inherited. It has been claimed that there is no mendelian basis for the condition but a rare report of its occurrence in a brother and sister raises the possibility of an autosomal recessive trait.⁴ It has also been reported in 2 siblings from a highly consanguineous marriage.⁵

• Suspicions can be raised at mid-trimester ultrasound scanning and the condition be diagnosed but it can also easily be missed.⁶
• The child may appear normal at birth or there may be problems such as poor development of male genitalia.
• Unexplained hypoglycaemia may suggest pituitary inadequacy.
• Vision testing and screening in young children may reveal the first sign of abnormality.
• Susceptibility to infection may suggest a problem and merit investigation.

A study of 228 patients from Australia found that there is a broad spectrum of pituitary problems ranging from isolated growth hormone deficiency to panhypopituitarism. About two-thirds of these patients have isolated hypopituitarism and 30% had all 3 manifestations with pituitary hypoplasia, optic nerve hypoplasia and agenesis of midline structures.⁷

Hormonal problems

• The most consistent clinical feature is short stature associated with poor or absent growth hormone. Weight and head circumference are normal for size.
• Lack of growth hormone and other pituitary hormones can make them susceptible to neonatal hypoglycaemia. There may also be hypernatraemia.
• Other pituitary hormones are often deficient and there may be diabetes insipidus although the posterior pituitary or neurohypophysis has a different embryological origin from the anterior pituitary of adenohypophysis.
• If there is illness, the lack of ACTH can precipitate an adrenal crisis and sudden death.

Other problems

• There are hypoplastic optic discs with a classical double margin. There may be blindness in one or both eyes and nystagmus.
• The septum pellucidum is usually absent. Other midline abnormalities may affect the corpus callosum and cerebellum.
• A majority of patients have some psychomotor impairment.
• Associations with autism have been described.
• Thermoregulation may be deficient.

Classification according to MRI findings⁸

A series of 55 patients divided them into 4 groups based on septum pellucidum and hypothalamic-pituitary axis appearance on MRI scan:

• In group 1 both were normal
• In group 2 there was abnormal septum pellucidum and normal hypothalamic-pituitary axis
• In group 3 there was normal septum pellucidum and abnormal hypothalamic-pituitary axis
• In group 4 both were abnormal

None of the patients in group 1 had endocrine dysfunction compared with 22% in group 2, 35% in group 3 and 56% in group 4. Group 2 was the commonest to experience precocious puberty.

• Brain imaging with MRI is an important investigation and an MRI to measure the size of the optic nerves can confirm the diagnosis.⁹ MRI will indicate the degree of structural abnormality and this indicates the likely endocrine abnormality.
• Tests of pituitary function may show hypopituitarism.
• Developmental assessment is likely to show retardation.

• Growth hormone may be administered.
• If ACTH is deficient the correct dose of cortisone to permit health and growth is a delicate balance.
• Management of puberty requires judgement.¹⁰ It may involve induction of puberty or delaying it if premature.
• Psychomotor retardation complicated by poor vision requires specialist help.

Appearance of the septum pellucidum and hypothalamic-pituitary axis on MRI predict the likely spectrum of endocrine disorder and prognosis is also dependent upon the degree of abnormality. Early diagnosis improves outcome.¹¹