1. Septo-Optic Dysplasia Tim Alves

2. Outline Overview Etiology Epidemiology Presentation Workup
Radiologic findings
Prognosis and Treatment
Key Points
References

3. Septo-optic dysplasia
Previously called De Morsier syndrome
Originally described in 1941 as an absence of the septum pellucidum with optic nerve abnormalities.
Later updated to include pituitary dysfunction
There is some controversy regarding diagnostic criteria, but generally it is a clinical diagnosis made when at least 2 of 3 classic criteria are met:
Optic nerve hypoplasia
Pituitary hormone abnormalities
Midline brain defects, including agenesis of the septum pellucidum and/or corpus callosum

4. Etiology Early forebrain developmental abnormality
Disorder of midline ventral prosencephalic development (~4th to 6th week of gestation) including optic nerves, forebrain, olfactory bulbs, septum pellucidum, corpus callosum, and pituitary gland
Most cases sporadic/idiopathic

5. Etiology, cont. Genetic basis? Environmental? Multifactorial
AD and AR patterns have been described, two genes identified – HESX1 and SOX2
Genetic diagnosis made in <1% of cases
Environmental?
Associated with maternal diabetes, quinidine ingestion, antiseizure medications, drug abuse, CMV infection, and congenital brain malformations
Multifactorial

6. Epidemiology
1 in 10,000 to 1 in 50,000
More common in children born to younger mothers and first-borns
M=F, no ethnic predilection

7. Uncertain classification
Heterogeneous, variable features and severity
Syndrome vs. complex
Continuum…
Milder form of lobar holoprosencephaly?
Milder forms of SOD?

8. Presentation Generally two presentations:
At birth, in association with multiple congenital anomalies – seizures, apnea, cyanosis, hypotonia, jaundice, microphallus
Later on in childhood, with growth failure and/or visual abnormalities
Approx. 50% do not have a schizencephaly – this group tends to present with endocrine dysfunction
Approx. 50% of patients with SOD have a schizencephaly and present with seizures, almost normal visual apparatus, generally normal endocrine function – “SOD plus”

9. Associated Clinical Findings
Developmental delay
Obesity
Anosmia
Seizures
SNHL
Visual impairment
Cardiac anomalies
Sleep disturbances
Precocious puberty

10. Diagnostic Workup
History – visual problems, symptoms of hormonal deficiencies, other congenital and developmental abnormalities
Opthalmologic exam – optic nerve hypoplasia
Tests of pituitary function
MR is the best imaging modality

11. MRI Findings in SOD
Optic nerve hypoplasia/dysplasia, unilateral or bilateral
Agenesis of the septum pellucidum
Abnormalities of the corpus callosum and hypothalamo-pituitary axis
Thin pituitary stalk, small anterior pituitary, posterior pituitary ectopia
Findings are variable, and also include…
Olfactory nerve hypoplasia, schizencephaly, cortical dysplasias and heterotopia.

12. MR shows absent septum pellucidum, typical flat ventricular roof, pointy frontal horns, absent pituitary stalk and ectopic posterior lobe.

13. Images show absent septum pellucidum, hypoplastic pituitary stalk and calloso-forniceal continuation.

14. Significantly hypoplastic right optic nerve, ipsilateral to close lip schizencephaly is probably not SOD.

15. The optic nerves are very small as is the optic chiasm and pituitary stalk, the septum pellucidum is absent.

16. Imaging Differential Diagnosis
Lobar holoprosencephaly – similar to SOD but has lack of separation (“fusion”) of cerebral hemispheres, SOD is considered by some to be a milder form of this disorder
Overlap syndromes – Optic-infundibular dysplasia (OID) - normal septum; Schizencephaly
Isolated ectopic posterior pituitary lobe –normal optic chiasm/nerves, normal septum
Kallmann Syndrome- absent or dysplastic olfactory nerves/ olfactory sulci, hypogonadotropic hypogonadism, occasionally associated with visual, septal, or pituitary abnormalities

17. Prognosis and Treatment
Variable morbidity and prognosis - depends on associated brain and pituitary malformations
Possible hypothalamic and pituitary crises – sudden death from hypocortisolism
Treatment: Hormone replacement therapy

18. Key points
Classically optic nerve hypoplasia, pituitary hormone abnormalities, and absent septum pellucidum
Disorder of early prosencephalic development with varying presentations and degrees of severity
Mainly a clinical diagnosis
Exact criteria and classification is debatable
Continuum?
Majority of cases are idiopathic/sporadic, but genetic and environmental causes have been identified
MRI of the brain plays a key role in diagnosis
Key findings
Quickly narrows down a broad clinical differential diagnosis

19. References
Adam, A. Grainger & Allison’s Diagnostic Radiology, 5th ed Ch 70, Malformations of commissural and related structures + Figure Barkovich AJ. Diagnostic Imaging: Pediatric Neuroradiology, 1st edition, Amirsys. I5: Castillo M. Neuroradiology Companion: Methods, Guidelines, and Imaging Fundamentals, 3rd ed p Hahn JS and Barnes PD. Neuroimaging advances in holoprosencephaly: Refining the spectrum of the midline malformation. Am J Med Genet C Semin Med Genet Feb 15;154C(1): Webb EA, Dattani MT. Septo-optic dysplasia. European Journal of Human Genetics. 2010; 18: