Septo-optic dysplasia complex: Clinical and radiological manifestations in Omani children

Abstract

Background:Septo-optic dysplasia (SOD), also known as de-Morsier's syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia (ONH), pituitary gland hypoplasia, and midline abnormalities of the brain including absence of septum pellucidum and corpus callosum dysgenesis. It is typically diagnosed in infancy and has a variable presentation that includes visual, neurologic, and/or hypothalamic-pituitary endocrine deficits.Purpose:To demonstrate the ophthalmic, endocrine, and neurologic spectrum of SOD in five Omani children and address the crucial role of high-resolution neuroimaging for its early and accurate diagnosis.Materials and Methods:A retrospective chart review was performed in 2010 of all children in the pediatric ophthalmology database of Sultan Qaboos University Hospital (SQUH) who were diagnosed to have ONH. All relevantdemographic, ophthalmic, neurologic, endocrine, and neuro-radiological manifestations were recorded in a data collection form. All previous neuroimaging results were reviewed by a neuro-radiologist.Results:Five patients (four males, one female) with the diagnosis of ONH were included in the study. They presented during the period 1998-2008. All patients were born at term, with normal birth weights to healthy mothers with insignificant antenatal history. Age at presentation ranged from three months to one year. Manifestations at presentation included severe visual impairment (5/5), neonatal hypoglycemia (3/5), seizure disorder (2/5), and failure to thrive (4/5). ONH was bilateral in 3/5 patients and unilateral in (2/5). Brain and orbit imaging revealed varying anomalies in all patients. These included absent septum pellucidum (3/5), severe corpus callosum agenesis (1/5), ectopic pituitary (5/5), falx cerebri deficiency (1/5), optic nerve hypoplasia (5/5), optic chiasmal hypoplasia (5/5), and olfactory tract hypoplasia (1/5). Endocrine deficits were detected in 4/5 patients (3 with panhypopituitarism, and 1 with growth hormone deficiency) and necessitated replacement therapy.Conclusion:SOD is a clinically heterogeneous disorder with a wide spectrum of ophthalmic, endocrine, and neurologic manifestations. All features might not be present in a single patient. A high consanguinity rate and lack of history of alcohol and drug use were observed in our cohort. Most affected children present first to the pediatrician with failure to thrive. Radiological confirmation of ONH necessitates high-resolution imaging and interpretation by an experienced neuro-radiologist. In our cohort, all patients with ONH had associated optic chiasmal hypoplasia. Early detection and treatment reduces disease-related morbidity, and can be life saving.

Cranial nerve I: clinical anatomy and beyond

“…There a significant phenotypical overlaps with other conditions like CHARGE-syndrome [84], combined pituitary hormone deficiency, and SOD [85]. Thus, the current data indicate that olfactory nerve, bulb and tract hypoplasia can be a part of septo-optic dysplasia or be an overlap with KS [86][87][88].…”

Genetic analysis of IRF6, a gene involved in craniofacial midline formation, in relation to pituitary and facial morphology of patients with idiopathic growth hormone deficiency

“…In 19 of them (61%), pituitary duplication was accompanied by cleft palate [ 19 ]. Another well-known association between pituitary problems and craniofacial midline defects is called septo-optic dysplasia, defined as the absence of the septum pellucidum combined with hypoplasia of the optic nerve and pituitary dysfunction [ 20 , 21 ].…”

Septo-optic dysplasia/de Morsier's syndrome

“…Septo-optic dysplasia (SOD), sometimes known as de Morsier's syndrome, is characterized by optic nerve hypoplasia, pituitary endocrine dysfunction, and midline brain abnormalities (agenesis of septum pellucidum or corpus callosum) [Figures 1 and 2 ]. [ 1 2 3 4 ] It is estimated an incidence of 1/10.000. [ 1 2 ] Etiology is uncertain; it is thought to be associated with genetic and environmental influences early in gestation.…”

“…[ 1 2 3 4 ] It is estimated an incidence of 1/10.000. [ 1 2 ] Etiology is uncertain; it is thought to be associated with genetic and environmental influences early in gestation. [ 3 4 5 ] Mutations in HESX1 and SOX2 genes have also been associated with SOD.…”

“…[ 3 4 5 ] Mutations in HESX1 and SOX2 genes have also been associated with SOD. [ 1 2 ] Hypopituitarism, hypothyroidism, hypogonadism, adrenal insufficiency, delayed growth, and development are common clinical presentations. [ 1 3 4 ] If not diagnosed and treated, SOD can lead to severe hypoglycemia, adrenal crisis, seizures, and sudden death.…”