Septo-optic dysplasia

Abstract

This review summarises the key clinical features of septo-optic dysplasia (SOD), the significant inroads that progress in genetics has made into our understanding of the aetiology of the condition over the last decade, and the pitfalls and challenges that we face in the management of these phenotypically variable patients.

Vascular Cerebral Anomalies Associated with Septo-Optic Dysplasia

“…Even if the sporadic occurrence of SOD remains unexplained, it has been suggested that SOD is the end result of several different genetic abnormalities or in utero injuries, such as vascular disruption 7 , viral infections 8 or maternal exposure to valproic acid 9 . Optic nerve hypoplasia is usually bilateral (88% of the cases) rather than unilateral and is often the first clinical presentation while endocrinological abnormalities may manifest later 10 . In rare cases, eye abnormalities may be severe, including microphthalmia or bilateral anophthalmia 8 .…”

Midbrain-Hindbrain Involvement in Septo-Optic Dysplasia

“…10 Midline brain defects classically consist of complete or partial absence of the septum pellucidum with fused midline fornices (60% of cases) and/or corpus callosum abnormalities, such as agenesis, dysplasia, or hypoplasia. 1,10,11 Pituitary gland malformations include anterior pituitary hypoplasia, ectopic posterior lobe, and/or thin or interrupted pituitary stalk. 3 Optic nerve hypoplasia is frequently associated with ocular anomalies such as coloboma, anophthalmia, and microphthalmia.…”

“…Classically, the diagnosis of SOD is made when 2 or more features of the classic triad of optic nerve hypoplasia, pituitary hormone abnormalities, and midline brain defects are present. 1 However, only one-third of patients present with all cardinal features of SOD. 3 Visual deficits due to optic nerve hypoplasia and ocular malformations are usually the first presenting sign, whereas endocrine dysfunction may become apparent later on.…”

“…Currently, genetic abnormalities are identified only in 1% of patients, whereas the etiology remains unclear in most. 1 However, an increasing number of early developmental transcription factors and associated pathway genes have been implicated in the etiology of SOD, ie, HESX1, SOX2, SOX3, OTX2, PROKR2, FGF1, and FGF8. [2][3][4] These genes are expressed in regions that determine the formation of forebrain and related midline structures, such as the hypothalamus and pituitary gland, and mutations in these genes are therefore associated with marked phenotypic heterogeneity.…”

“…3 Visual deficits due to optic nerve hypoplasia and ocular malformations are usually the first presenting sign, whereas endocrine dysfunction may become apparent later on. 1 The severity of pituitary-hypothalamic dysfunction is highly variable, ranging from isolated deficit of pituitary hormones to panhypopituitarism. 3 Neurologic deficits are common, and range from global retardation to focal deficits such as epilepsy or hemiparesis.…”