Septo-optic dysplasia

Septo-optic dysplasia (SOD), (de Morsier syndrome)^[1][2] is a rare congenital malformation syndrome featuring underdevelopment of the optic nerve, pituitary gland dysfunction, and absence of the septum pellucidum (a midline part of the brain). Two of these features need to be present for a clinical diagnosis — only 30% of patients have all three.^[3]

Neuroradiologically, intracranial malformations associated with septo-optic dysplasia include agenesis of the septum pellucidum, schizencephaly, and lobar holoprosencephaly.

Presentation

Optic nerve

The optic nerve hypoplasia is generally manifested by nystagmus (involuntary eye movements, often side-to-side) and a smaller-than-usual optic disc. The degree of visual impairment is variable, and ranges from normal vision to complete blindness. When nystagmus develops, it typically appears by 1–8 months of age, and usually indicates that there will be a significant degree of visual impairment, but the severity is difficult to predict in infancy. Although there are many measures to compensate for visual impairment, there are few treatments available to induce normal optic nerve function.^[4]

Pituitary

The degree of pituitary deficiency is also variable, and ranges from normal function, to deficiency of both anterior and posterior hormones. It is often unclear if the hypopituitarism is due to a primary pituitary dysfunction or is secondary to a hypothalamic dysfunction. Hypopituitarism in this syndrome is most often manifested by growth hormone deficiency. If severe, it can lead to diagnosis in the first days of life by causing hypoglycemia, jaundice, and micropenis (if a boy). The cause of the jaundice is unknown, and an unusual aspect of it (compared to most neonatal jaundice) is that it can be largely a conjugated (direct) hyperbilirubinemia suggestive of obstructive liver disease. It typically resolves over several weeks once hormone replacement is begun. All of the pituitary hormones can be replaced, and this is the treatment for deficiencies. Septo-optic dysplasia is one of the most common forms of congenital growth hormone deficiency.

Septum pellucidum

The brain effects are also variable. Seizures sometimes occur. Prediction of intellectual outcome in infancy is difficult. Various types of early intervention or equivalent programs can help a child reach full developmental potential.

Variability

Septo-optic dysplasia is a highly variable disorder. It is rare for siblings to present with identical features of the septo-optic dysplasia spectrum. Many patients present with additional developmental defects outside the septo-optic dysplasia triad. In particular digital defects are common.

Causes

Septo-optic dysplasia is a developmental disorder resulting from a defect of normal embryological development. There is no single cause of septo-optic dysplasia. Septo-optic dysplasia has been linked to young maternal age.^[5]

Genetic

Rare familial recurrence has been reported, suggesting at least one genetic form (HESX1).^[6] In addition to HESX1, mutations in OTX2, SOX2 and PAX6 have been implicated in de Morsier syndrome,^[7] but in most cases SOD is a sporadic birth defect of unknown cause and does not recur with subsequent pregnancies.

Valproate toxicity

Valproate toxicity in utero has been implicated as a possible etiology of septo-optic dysplasia.^[8]

References