Jia Xuan Tan
Introduction
Septo-optic dysplasia (SOD), previously known as de Morsier syndrome, is a rare congenital disorder that is characterized by a triad of optic nerve hypoplasia, pituitary hormone dysfunction and midline brain abnormalities (typically agenesis or hypoplasia of septum pellucidum and/or corpus callosum) (1). The diagnosis is clinical and can be made when at least two features of the triad are fulfilled. Epidemiological studies estimate its prevalence between 1.9 and 2.5 per 100,000 live births (1). Early recognition and a coordinated multidisciplinary approach and essential to reduce morbidity and mortality. In particular, timely identification of endocrine dysfunction prevents life-threatening adrenal crises and growth disturbances which early vision and developmental support enhance long-term functional outcomes (2).
Pathophysiology
SOD arises from abnormal embryologic development of the anterior midline brain structures and optic nerves in early gestation, typically between the fourth and sixth weeks of embryonic life (3). The exact cause is multifactorial and remains incompletely understood.
Pathogenic variants in several transcription factors important for forebrain and pituitary development such as HESX1, SOX2, SOX3, OTX2 and PAX6 have been reported in several cases (4). These genes regulate the differentiation of neural and pituitary progenitor cells, and their disruption can impair the growth of the optic nerves and hypothalamo-pituitary axis.
Environmental exposures during pregnancy including infection, maternal diabetes, drug or toxin exposure have been proposed as contributing factors (4).
Clinical features
The clinical spectrum of SOD is broad and variable. Only 30% of patients present with the full triad; most have two features or an incomplete phenotype (2). Manifestations may be evident at birth or emerge gradually during infancy and early childhood.
Optic nerve hypoplasia is the most common and often the earliest recognised feature. Most patients present with worsening visual acuity and nystagmus. Other associated ocular findings include foveal hypoplasia, strabismus, refractive error and cortical visual impairment may co-exist and contribute to poor functional vision.
Midline abnormalities of the brain in SOD could include agenesis of corpus callosum and septum pellucidum. This may manifest as global developmental delay, motor deficits, seizures and behavioural and neuropsychiatric features (5).
Pituitary hormone deficiency is among the most clinically significant features of SOD. Deficits can include central hypothyroidism being the most common, followed by growth hormone deficiency, adrenal insufficiency and diabetes insipidus (4). Endocrine insufficiency can present at birth or arise later therefore ongoing surveillance is essential to ensure timely hormone replacement.
Investigation
A systematic diagnostic work-up is vital for suspected SOD.
Comprehensive ophthalmic assessments include visual acuity evaluation and fundus examination are helpful in detecting mild optic nerve hypoplasia (6).
Magnetic resonance imaging (MRI) is the recommended modality to evaluate optic nerves/chiasm, septum pellucidum, corpus callosum and pituitary gland.
Prompt referral to paediatric endocrinology is essential for baseline hormonal assessment and initial biochemical screening including glucose, serum sodium and hormone panels.
Management
There is currently no curative therapy for SOD. Management is directed toward minimizing complications and optimizing function through a multidisciplinary team approach.
Endocrinology management includes hormone replacement tailored to specific deficiencies (e.g. Levothyroxine for central hypothyroidism, recombinant growth hormone for GH deficiency, hydrocortisone for ACTH deficiency and desmopressin for diabetes insipidus) is crucial for maintaining metabolic stability and normal growth (7).
Early involvement of Ophthalmology and low-vision services facilitates visual development. Corrective lenses, amblyopia therapy and management of strabismus or refractive errors may improve functional vision (2).
Neurology and neuropsychology play a vital role in managing complications including seizures, motor impairments and cognitive or behavioural difficulties. Ongoing neuropsychological assessment helps to identify learning and language challenges early and to guide individualized intervention and educational planning for affected children (2).
Conclusion
Septo-optic dysplasia represents a complex developmental disorder with highly variable presentation and prognosis. Coordinated multidisciplinary management is essential to treat endocrine, visual, and neurodevelopmental complications. Ophthalmologists play a pivotal role in early recognition through identification of optic nerve hypoplasia and prompt referral for neuroimaging and endocrine evaluation. Early diagnosis, proactive hormone management, and comprehensive rehabilitative care significantly improve quality of life and long-term outcomes for affected individuals.
Reference
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- Sataite I, Cudlip S, Jayamohan J, Ganau M. Septo-optic dysplasia. Handbook of Clinical Neurology. 2021 Jan 1;181:51-64.
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- Mann A, Aghababaie A, Kalitsi J, Martins D, Paloyelis Y, Kapoor RR. Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review. Molecular Autism. 2023 Jul 25;14(1):26.