Does asymptomatic septal agenesis exist? A review of 34 cases
Background: Primary septal agenesis (PSA) is a rare brain malformation that can be isolated or part of developmental brain abnormalities (holoprosencephaly, septo-optic dysplasia or cortical malformation). Such associated malformation can be subtle, leading to difficulties in the prenatal management of PSA. Moreover, the neurological prognosis of isolated PSA remains debatable. Objective: The aims of the study were to specify the patterns and frequency of brain malformations associated with septal agenesis (SA), to identify the clinical prognosis, and to discuss the aetiology of PSA with the new insights provided by molecular genetics. Materials and methods: The study consisted of a 14-year retrospective review of brain MRI in 34 patients having PSA (mean age, 5 years). Chiasm and optic nerves were not evaluated. Post-hydrocephalus SA or incomplete data were excluded. The clinical data were correlated to the MRI patterns. Results: The study disclosed 82.5% associated lesions with MRI (28/34): 11 neuronal migration disorders, 9 holoprosencephalies (HP), 7 pituitary stalk interruptions, 1 corpus callosum partial agenesis; 17.5% (6/34) of cases were apparently isolated PAS. Clinically, the patients had motor dysfunction in 68% (23/34), mental retardation in 65% (22/34), blindness in 24% (8/34), endocrinological defects in 21% (7/34) and epilepsy in 18% (6/34) of cases. Nine percent of patients (3/34) were neurologically normal (including one with scoliosis and two infants younger than 2 years at the last follow-up). Patients with bilateral cortical anomalies and HP (even if mild) had the worst neurological prognosis. A severe motor impairment was present without evidence of hemispheric anomaly in 12% of patients (4/34). Interestingly, the frontal lobes were involved in 90% of cortical anomalies and HP, supporting the malformative aetiology of PSA. Conclusions: PSA rarely appears isolated and severe psychomotor impairment may occur in apparently isolated forms. These unfavourable results should be highlighted and need to be confirmed by a prospective study.
KeywordsCongenital Brain Septum pellucidum Holoprosencephaly Septo-optic dysplasia MRI Children
Special thanks to Sylvie Odent for her references about the genetics of holoprosencephaly, to our colleagues in the paediatric neurology and paediatric endocrinology departments and to Pascale Zerbini for preparing the manuscript.
- 2.Kuhn MJ, Swenson LC, Youssef HT (1993) Absence of the septum pellucidum and related disorders. Comput Med Imaging Graph 17:137–147Google Scholar
- 3.Cihangiroglu M, Bulut S, Yilmaz S (2002) Isolated septum pellucidum agenesis in an adult. J Neuroimaging 12:89–91Google Scholar
- 4.Supprian T, Sian J, Heils A, et al (1999) Isolated absence of the septum pellucidum. Neuroradiology 41:563–566Google Scholar
- 5.De Morsier G (1956) Etudes sur les dystrophies crânio-encéphaliques III. Agénésie du septum pellucidum avec malformation du tractus optique: la dysplasie septo-optique. Schweiz Arch Neurol Neurochir Psychiatr 77:267–292Google Scholar
- 6.Hoyt WF, Kaplan SL, Grumbach MM, et al (1970) Septo-optic dysplasia and pituitary dwarfism. Lancet 1(7652):893–894Google Scholar
- 17.Siatkowski RM, Sanchez JC, Andrade R, et al (1997) The clinical, neuroradiographic, and endocrinologic profile of patients with bilateral optic nerve hypoplasia. Ophthalmology 104:493–496Google Scholar
- 19.Brunelli S, Faiella A, Capra V, et al (1996) Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly. Nat Genet 12:94–96Google Scholar
- 20.Barkovich AJ, Kjos BO (1992) Schizencephaly: correlation of clinical findings with MR characteristics. AJNR 13:85–94Google Scholar
- 21.Dattani ML, Martinez-Barbera J, Thomas PQ, et al (2000) Molecular genetics of septo-optic dysplasia. Horm Res 53 [Suppl 1]:26–33Google Scholar