Agenesis of Septum Pellucidum

Q04.3, Q04.4

Septo-optic dysplasia, De Morsier Syndrome

Holoprosencephaly, agenesis of corpus callosum, schizencephaly

Absence of the septum pellucidum; when this is associated with optic disc hypoplasia and hypopituatism, the condition is defined septo-optic dysplasia (or De Morsier syndrome).

Agenesis of the septum pellucidum (ASP) is found with many other brain anomalies, including mostly holoprosencephaly and schizencephaly ^{1, 2}. ³. Severe ventriculomegaly and Arnold-Chiari malformation are frequently associated with secondary disruption of the septum pellucidum. Apparently isolated cases of ASP may be due to septo-optic dysplasia (SOD) or represent an isolated anomaly. SOD, which also known as De Morsier syndrome, is a rare condition characterized by agenesis of the septum pellucidum  and hypoplasia of the optic nerve, chiasm and pituitary gland. 

Ventriculomegaly, schizencephaly, agenesis of the corpus callosum, cranio-facial anomalies such as hypothelorism and clefting

Unknown. SOD can be caused by a mutation in the homeobox gene HESX1 or occur because of exposure to teratogens or viral infections.⁴. Most cases are sporadic. Hereditary cases have however been reported, that were compatible with both autosomal recessive and autosomal dominant transmission ^4-7    

The risk of recurrence is low, albeit a few cases suggesting mendelian transmission have been described.

Well formed forntal horns that  divaricate anteriorly with otherwise normal cerebral structures, including a regular corpus callosum favor the diagnosis of absence of the septum pellucidum versus lobar holoprosencephaly. After birth, a definitive diagnosis of septo-optic hypoplasia is made by the CT or MRI demonstration of optic tract hypoplasia, endocrine evaluation and visual assessment. In the fetus, the differential diagnosis between SOD and isolated ASP may be attempted by evaluation of maternal urine and serum estriol levels; fetal blood assays for growth hormone, ACTH and prolactin; and visualization of the optic nerve size as depicted by MRI in a search for optic nerve hypoplasia.⁸ More recently, 3D ultrasound has been used to visualize the optic chiasm.¹² Normal measurements of the posterior optic tracts have been reported and in a rather large series of fetuses affected by agenesis of the septum pellucidum these measurements effectively predicted visual impairment and/or optic tract hypoplasia.¹³.On the basis of the available experience it would seem therefore that 3D ultarsound is the best method to discriminate between simple agenesis of the septum pellucidum and septo-optic dysplasia. However, the experience is limited and certainly the technique for visualizing and measuring the optic tracts is difficult to master.

Many fetuses with absence of the septum pellucidum have severe cerebral anomalies such as holoprosencephaly and schizencephaly that are rapidly recognized and carry a poor prognosis. Isolated agenesis of the septum pellucidum may have a normal outcome ⁹ but may also be associated with SOD.^{8, 13, 14} The outcome of individuals affected by SOD is variable. The optic nerves and chiasm are affected by different degrees of hypoplasia, resulting in poor vision and nystagmus . A subset of these infant is blind, but usually will develop a modest degree of vision function in later life. Signs of both anterior and posterior hypopituitarism are always present. However intelligence tends to be within normal limits. Of 7 infants with isolated septo-optic dysplasia, with no other brain abnormalities, only one was found to have moderate cognitive and language delays.¹⁵ The available experience suggests that in a fetus with absence of the septum pellucidum, there is roughly a 25% chance of SOD.^{13, 14} Low levels of maternal estriol as well as MR or 3D ultrasound demonstration of small optic tracts are associated with a much increased risk of SOD. Even when these findings are normal, it is not possible to rule out SOD.

Standard obstetric care.

1.         Belhocine O, Andre C, Kalifa G, Adamsbaum C. Does asymptomatic septal agenesis exist? A review of 34 cases. Pediatr Radiol 2005;35(4):410-8.

2.         Malinger G, Lev D, Kidron D, Heredia F, Hershkovitz R, Lerman-Sagie T. Differential diagnosis in fetuses with absent septum pellucidum. Ultrasound Obstet Gynecol 2005;25(1):42-9.

3.         Raybaud C, Girard N, Levrier O, Peretti-Viton P, Manera L, Farnarie rP. Schizencephaly: correlation between the lobar topography of the cleft(s) and absence of the septum pellucidum. Childs Nerv Syst. 2001;17(4-5):217-222.

4.         Dattani ML, Martinez-Barbera J, Thomas PQ, Brickman JM, Gupta R, Wales JK, Hindmarsh PC, Beddington RS, Robinson IC. Molecular genetics of septo-optic dysplasia. Horm Res 2000;53 Suppl 1:26-33.

5.         Kelberman D, Dattani MT. Septo-optic dysplasia - novel insights into the aetiology. Horm Res 2008;69(5):257-65.

6.         McCabe MJ, Alatzoglou KS, Dattani MT. Septo-optic dysplasia and other midline defects: the role of transcription factors: HESX1 and beyond. Best Pract Res Clin Endocrinol Metab;25(1):115-24.

7.         Wales JK, Quarrell OW. Evidence for possible Mendelian inheritance of septo-optic dysplasia. Acta Paediatr 1996;85(3):391-2.

8.         Lepinard C, Coutant R, Boussion F, Loisel D, Delorme B, Biquard F, Bonneau D, Guichet A, Descamps P. Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia. Ultrasound Obstet Gynecol 2005;25(1):73-5.

9.         Celentano C, Prefumo F, Liberati M, Tartaro A, Gallo G, Lattanzio G, Rotmensch S. Prenatal diagnosis of septal agenesis with normal pituitary function. Prenat Diagn. 2006;26(11):1075-1077.

10.        Pilu G, Sandri F, Cerisoli M, Alvisi C, Salvioli GP, Bovicelli L. Sonographic findings in septo-optic dysplasia in the fetus and newborn infant. Am J Perinatol 1990;7(4):337-9.

11.        Pilu G, Tani G, Carletti A, Malaigia S, Ghi T, Rizzo N. Difficult early sonographic diagnosis of absence of the fetal septum pellucidum. Ultrasound Obstet Gynecol 2005;25(1):70-2.

12.        Bault JP. Visualization of the fetal optic chiasma using three-dimensional ultrasound imaging. Ultrasound Obstet Gynecol 2006;28(6):862-4.

13.        Bault JP, Salomon LJ, Guibaud L, Achiron R. Role of three-dimensional ultrasound measurement of the optic tract in fetuses with agenesis of the septum pellucidum. Ultrasound Obstet Gynecol;37(5):570-5.

14.        Damaj L, Bruneau B, Ferry M, Moutard ML, Garel C, Odent S, Adamsbaum C, Avni F, Treguier C, Lazaro L. Pediatric outcome of children with the prenatal diagnosis of isolated septal agenesis. Prenat Diagn;30(12-13):1143-50.

15.        Williams J, Brodsky MC, Griebel M, Glasier CM, Caldwell D, Thomas P. Septo-optic dysplasia: the clinical insignificance of an absent septum pellucidum. Dev Med Child Neurol 1993;35(6):490-501.

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