Disease relevance of Septo-Optic Dysplasia

• He suffered from septo-optic dysplasia, retinitis pigmentosa, exercise intolerance, hypertrophic cardiomyopathy, and rhabdomyolysis [1].
• Midline brain defects (septo-optic dysplasia, 28; holoprosencephaly, 2) and combined pituitary hormone deficiencies were present in 30 and 52 patients, respectively [2].
• The following patient groups were chosen to represent various clinical conditions affecting the newborn or fetus at different stages of development: children born preterm (N = 39), children with fetal alcohol syndrome (FAS [N = 16]), children with periventricular leukomalacia (PVL [N = 17]), and children with septo-optic dysplasia (SOD [N = 6]) [3].
• Optic nerve hypoplasia has been reported in association with other prenatal anticonvulsant exposures, but the occurrence of septo-optic dysplasia as a manifestation of valproic acid embryopathy has not been reported previously [4].
• Mutations in some of these genes have revealed a spectrum of pathology similar to that observed in septo-optic dysplasia, Möebius syndrome, and Duane retraction syndrome [5].

High impact information on Septo-Optic Dysplasia

• Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse [6].
• Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia [7].
• Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation [1].
• Septo-optic dysplasia and WS1 in the proband of a WS1 family segregating for a novel mutation in PAX3 exon 7 [8].
• Arrhythmicity in a child with septo-optic dysplasia and establishment of sleep-wake cyclicity with melatonin [9].

Chemical compound and disease context of Septo-Optic Dysplasia

• CONCLUSIONS: We report the first case of septo-optic dysplasia associated with maternal exposure to valproic acid throughout pregnancy [4].
• Hypothalamic pituitary function and growth hormone releasing hormone (GHRH) loading tests in two children with septo-optic dysplasia (SOD) revealed isolated GH deficiency in one and deficiencies of growth hormone, adrenocorticotropic hormone and antidiuretic hormone in the other [10].
• Delaying puberty is an option in septo-optic dysplasia, and minimising the dose of hydrocortisone is crucial in treating ACTH/cortisol insufficiency [11].

Biological context of Septo-Optic Dysplasia

• Mutations in the novel homeobox gene Hesx1/HESX1 are associated with the highly variable phenotype of septo-optic dysplasia in mouse and man [12].

Anatomical context of Septo-Optic Dysplasia

• Magnetic resonance imaging of pituitary stalk hypoplasia. A discrete midline anomaly associated with endocrine abnormalities in septo-optic dysplasia [13].
• The changes in the former are consistent with those previously described as craniotelencephalic dysplasia and those in the latter indicate primary developmental abnormalities of the central nervous system including septo-optic dysplasia, absent olfactory nerves, agenesis of the corpus callosum, and lissencephaly [14].

Gene context of Septo-Optic Dysplasia

• Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia [15].
• OBJECTIVES: Mutations in the genes encoding the transcription factors PROP1 and POUF-1 (Pit-1) have been reported as common causes of combined pituitary hormone deficiency (CPHD), and HESX1 mutations have been identified in children with septo-optic dysplasia (SOD) [15].
• This is the first reported case of a patient with septo-optic dysplasia who underwent corticotropin-releasing factor and growth hormone-releasing hormone stimulation [16].
• Eighty-one percent met classic criteria for GH deficiency and were classified as having idiopathic GH deficiency (59%), organic GH deficiency (18%), or septo-optic dysplasia (4%) [17].
• In contrast to previous reports, endocrine abnormalities were seen in only one quarter of patients, and the full-blown deMorsier syndrome (septo-optic dysplasia with panhypopituitarism) was seen in only 11.5% of patients with BONH [18].

References