52 Pathology-Based Diagnoses: Congenital Malformations infundibulum isnotseen. adolescent, andthe pituitary glandissmallforan eminence. Notethatthe gland statthemedian posterior lobeofthepituitary fornices ſt)andtheectopic pellucidum (notethelow-lying MR showsabsentseptum small. ﬊, andtheopticchiasmſtis inferiorly aroundthefornices anterior hornsaredraped septum pellucidum.The the absenceofamidline flat-roofed anteriorhornsand (Left) is normal. sheath. Theleftopticnervest through asmallopticnerve nerve ſtistiny,running hypoplasia. Therightoptic shows unilateralopticnerve the intraorbitalopticnerves same patientatthelevelof Coronal T2WIFSEMRinthe dysplasia (SOD). is oftenthecaseinseptooptic chiasm ﬇isnormalinsize,as fornices. Notethattheoptic frontal horns,drapedover the inferiormarginsof pellucidum andpointingſtof shows theabsenceofseptum (Left) Newborns: Hypoglycemic• seizures, apnea, cyanosis, CLINICAL ISSUES 3 orthogonal planes crucial• to identify all findin Coronal imaging shows• Optic nerves, pituitary• gland, septum pellucidum Absent septum pellucidum,• small optic chiasm IMAGING De Morsier syndrome• Septooptic dysplasia (SOD)• TERMINOLOGY Absent septum pellucidum,○ flat roof of frontal hor microphallus hypotonia, prolonged conjugated jaundice, and (in b Downward pointing anterior○ horns Flat-roofed ventricles○ small optic chiasm Coronal graphicdepicts Coronal T2WIFSEMR (Right) Sagittal T1WI (Right) Septooptic Dysplasia gs oys) ns, KEY FACTS SOD in small stature pediatric• patient with absent DIAGNOSTIC CHECKLIST Small optic nerves, with• ectopic posterior pituita Abnormal endocrine function• (60%): Look for multip Bilateral optic nerve • hypoplasia (70%) 75-90% have brain abnormalities;• 45% have pituitar ± mental retardation, • spasticity, , an Normal or color blindness,• visual loss, nystagmus, Child with short stature,• endocrine dysfunction Normal endocrine function• (40%): Often have with absent septum pellucidum pellucidum insufficiency strabismus schizencephaly, seizures pituitary deficiencies ry lobe, o s m i a septum y le Pathology-Based Diagnoses: 53 Congenital Malformations t e see ts nation gene HESX1 to cerebral lesion cerebral to development gestation diabetes maternal alcohol, variant) small pons, thick quadrigeminal plate, vermian plate, quadrigeminal thick pons, small componen underrecognized but significant dysplasia) spectrum SOD of phenotypes – Or vascular disruption (field defect) during brain during defect) (field – disruption vascular Or week 6th around nerve optic – and cerebral to Damage drugs, antiepileptic –, Teratogens: – Midline heritable defect (mild (mild –defect heritable Midline du fibers nerve optic of –degeneration secondary Or – heterotopia, ± midbrain, (short –abnormalities Midbrain-hindbrain dynamic MR dynamic – Homozygous mutations = full syndrome full – = mutations Homozygous pituitary milder = – mutations Heterozygous optic nerves optic ○sporadic are Most recessive or dominant ○ autosomal are Some in ○mutations have cases Some ○ Many consider it same disorder as SOD as disorder ○same it consider Many ○ Theories ○ MR sella/orbi through sections ○thin sagittal Coronal, better to CISS/FIESTA/SPACE or ○ saturation fat Use ○ Deficient falx (especially anteriorly) ± hypomyeli ± anteriorly) ○(especially falx Deficient ○ ± ectopic posterior pituitary lobe pituitary ○posterior ectopic on ± lobe pituitary anterior of ○enhancement Delayed PATHOLOGY DIFFERENTIAL DIAGNOSIS DIFFERENTIAL • Genetics • Optic-infundibular dysplasia, normal septum normal •dysplasia, Optic-infundibular septum •absent with Schizencephaly Syndrome Kallmann •nerves olfactory Absent abnormalities •pituitary septal, visual, ± Holoprosencephaly •SOD to Similar Lobe Pituitary Posterior Ectopic Isolated pellucidum septum • chiasm/nerves, Normal • Etiology Angiographic Findings Angiographic • Conventional Recommendations Imaging •tool imaging Best •advice Protocol • T2WI •C+ T1WI General Features General Syndromes Overlapping With Septooptic Dysplasia Septooptic With Overlapping Syndromes aly ging t of t erve uitary gs as Septooptic Dysplasia Septooptic fornices frontal horns frontal nerves) optic of visualization present) –ectopia pituitary posterior ± midline fused or –continuation Callosal-forniceal –callosum corpus Thin –hippocampi Vertical nerves –olfactory hypoplastic/absent ± –schizencephaly ± – Small optic chiasm/nerves (fat saturation aides saturation (fat –chiasm/nerves optic Small pit of lobe anterior small –stalk, pituitary thin ± –ventricles Flat-roofed horns –anterior Downward-pointing – Absent septum pellucidum (remnants may be may (remnants –pellucidum septum Absent aspec inferior pointed –horns, frontal of roof Flat hypopituitarism pellucidum, pituitary gland, plus cortical dysplasi cortical plus gland, pituitary pellucidum, to overlap to ○ 3 orthogonal planes crucial to identify all findin all identify to crucial ○planes orthogonal 3 ○pellucidum septum Absent ○ventricles lateral ima Large coronal and axial on ○foramina optic bony Small ○shows imaging Coronal ○nerves optic Small lobe posterior ectopic with ○gland pituitary Small ○pellucidum septum Absent ○ Optic nerves, pituitary gland, septum pellucidum septum gland, ○pituitary nerves, Optic ○ Absent septum pellucidum, small optic chiasm optic small ○pellucidum, septum Absent hypoplasia (ONH), absent septum pellucidum, septum absent (ONH), hypoplasia dysfunction hypothalamic-pituitary SOD with patients 7 Described ○ (1956): Morsier De with SOD of association ○Described (1978): Hoyt IMAGING TERMINOLOGY • SOD plus: Abnormal optic nerves/chiasm, septum nerves/chiasm, •optic Abnormal plus: SOD General Features General Abbreviations MR Findings MR • T1WI CT Findings CT • NECT • Morphology • Size • Location •clue diagnostic Best Definitions n optic by characterized •association Heterogeneous •syndrome Morsier De •syndrome Kaplan-Grumbach-Hoyt •dysgenesis Suprasellar •dysgenesis Septooptic-pituitary •(SOD) dysplasia Septooptic Synonyms • Some authors consider SOD and lobar holoprosenceph lobar and SOD • consider authors Some 54 Pathology-Based Diagnoses: Congenital Malformations Geniculate nucleus (if• found): Disorganized layeri Associated abnormalities• Presentation Age• Demographics Most common signs/symptoms• Optic nerves, chiasm have• sparse or absent myelina Microscopic Features Forniceal columns (± fused)• → run along roof of Deficient/absent 3r septum• pellucidum Small or absent geniculate• nucleus Small optic chiasm/nerves• Gross Pathologic & Surgical Features Isolated ONH: Visual defect• only; intelligence and Staging, Grading, & Classification Common: Hypoplasia pituitary,• olfactory lobes Intrauterine or perinatal• insult (especially menin Complete septal agenesis:• Worse developmental prog ONH and septal and pituitary• deficiency: May have ONH and septal deficiency:• Same as isolated Clinical profile• CLINICAL ISSUES fibers Frequently associated○ with other cerebral anomalie Mutations of ○ Inactivation of ○ Generally detected ○ in infants Abnormal endocrine ○ function (60%): Look for multip Newborns: Hypoglycemic○ seizures, apnea, cyanosis, neurons deficiency cause of optic nerve, chiasmatic, and hypothalamic Overlapping syndromes○ with optic, septal, frontal Normal endocrine function○ (40%): Often have ventricle developmental delay normal ± mental retardation,○ spasticity, microcephaly, an Normal or color blindness,○ visual loss, nystagmus, Child with short stature,○ endocrine dysfunction (does not occur in sporadic SOD) substitution leads to deficient anterior pituitary microphallus hypotonia, prolonged conjugated jaundice, and (in b Incomplete hippocampal – rotation Olfactory tract/bulb hypoplasia– Ocular anomalies (coloboma,– anophthalmia, Midline malformations (callosal– dysgenesis, etc.) Perisylvian polymicrogyria– Most common = schizencephaly– schizencephaly, seizures pituitary deficiencies strabismus midline, olfactory deficiencies microphthalmia) F G F R 1 H E S X 1 , PROKR2 (3p21.2-3p21.2) by Arg53Cys also described Septooptic Dysplasia gitis) as ng of small growth d lobe ted o s m i a lobe, s nosis oys) le Hormonal replacement therapy• Treatment Depends upon severity • of associated brain and pitu Hypothalamic and pituitary• crises; sudden death Natural History & Prognosis .Cemeroglu AP et al: Spectrum of clinical1. presentat Small optic nerves, + • ectopic posterior pituitary Image Interpretation Pearls SOD in small stature pediatric• patient with absent Consider .Bancalari RE et al: Pituitary gland development:6. a Epidemiology• Gender • .Signorini SG et al: Septo-optic dysplasia8. in child .Winter TC et al: Holoprosencephaly: a 2. survey of th .Raivio T et al: Genetic overlap in Kallmann7. syndro 3 Camino R et al: Septo-optic13. dysplasia plus. Lancet .García-Arreza A et al: Isolated absence5. of septum .Volpe P et al: Disorders of prosencephalic9. develop 2 Riedl S et al: Refining12. clinical phenotypes in sep .Garcia-Filion P et al: Optic nerve hypoplasia4. synd 1 Hung JH et al: Prenatal11. diagnosis of schizencephal .Severino M et al: Midbrain-hindbrain involvement3. i 0 Borchert M et al: The 10. syndrome of optic nerve hypo SELECTED REFERENCES DIAGNOSTIC CHECKLIST absent septum pellucidum malformations (hypocortisolism) Septooptic dysplasia○ ○ 1 in 50,000 worldwide○ M = F○ More common among younger○ mothers and 1st born pellucidum 97(4):E694-9, 2012hormone deficiency, and septo-optic dysplasia. J Cl Pediatr Endocrinol Metab. ePub, 2015findings of patients with septo-optic dysplasia: a 15, 2012 diagnosis and outcome. Fetal Diagn Ther. 33(2):130- MRI findings. Eur J Pediatr. 167(11):1269-76, 2008 89, 2013 epidemiology and clinical associations. Curr Treat 54(11):1018-24, 2012cognitive and neuro-ophthalmological perspective. D Res. 34(4 Pt 2):674-9, 2008dysplasia by ultrasound and magnetic resonance imag AJNR Am J Neuroradiol. 35(8):1586-92, 2014 and fetal imaging. Radiographics. 35(1):275-90, 201 Neurosci Rep. 8(5):395-403, 2008 29(4):340-354, 2009 75-90% have brain abnormalities;– 45% have pituitar 25-50% have absent septum– pellucidum 60% have brain abnormalities– (not just child Bilateral optic nerve hypoplasia– (70%) 30% have both□ schizencephaly); 62-88% have pituitary insufficienc insufficiency hood: the neurological, to-optic dysplasia based on rome: a review of the retrospective study. J me, combined pituitary n update. Endocr Dev. 23:1- Neurol. 2(7):436, 2003 pellucidum: prenatal Options Neurol. 15(1):78- e entity, with embryology y with septo-optic ment. Prenat Diagn. n septo-optic dysplasia. ions and endocrinological in Endocrinol Metab. 5 plasia. Curr Neurol 2, 2013 ev Med Child Neurol. ing. J Obstet Gynaecol lobe, plus septum i t a r y y y