Absent cavum with intact septum pellucidum and corpus callosum may indicate midline brain abnormalities

Abstract

In a recent publication of a series of cases of absence of a visible cavum detected prenatally, Malinger et al.1 concluded that this finding is not always associated with callosal anomalies and may represent a variation of normal development with good postnatal outcome. Although this may be true in a proportion of cases, we would like to point out that absence of fluid in the cavum, with intact septum pellucidum and corpus callosum, potentially indicates subtle midline brain abnormalities that may have significant implications for perinatal management and postnatal neurological development. A 28-year-old woman presented for screening ultrasound at 19 + 4 weeks' gestation following isolated low unconjugated estriol level (0.29 multiples of the median) on serum screening for Down syndrome. Transvaginal sonography demonstrated absence of fluid within the cavum septi pellucidi but normal ventricular and callosal appearance. Follow-up ultrasound at 21 + 4 weeks confirmed these findings. Karyotyping performed on cultured amniocytes was normal. Smith–Lemli–Opitz syndrome was excluded by normal amniotic fluid 7-dehydrocholesterol level. A follow-up scan at 23 weeks showed no fluid within the cavum septi pellucidi (Figure 1). Transvaginal visualization of the corpus callosum demonstrated normal length, with possible subtle dysmorphic appearance of the splenium (Figure 2). A male infant was delivered by Cesarean section at 41 weeks after three failed inductions. Apgar scores were 3, 5 and 7 at 1, 5 and 10 min, respectively, and cord pH was 7.09. Respiratory effort was poor and he was transferred to the nursery due to mild respiratory distress. His blood glucose on arrival was < 1 mmol/L. He required two boluses of D10W and remained on D10W infusion for 48 h to achieve stabilization before discharge. He was readmitted at 11 days of age with persistent hyperbilirubinemia, low blood glucose level and weight loss. A diagnosis of cortisol deficiency, growth hormone deficiency and hypothyroidism was made, as well as, subsequently, diabetes insipidus. The adrenal insufficiency explained the prenatally detected low unconjugated estriol. Optic nerve hypoplasia was apparent on ophthalmological examination. Magnetic resonance imaging at 10 months of age showed vestigial prechiasmatic optic nerves and optic chiasm, as well as complete absence of pituitary tissue. There was posterior callosal dysgenesis. At the time of writing, he was 2 years old and was being followed for global developmental delay, hypotonia, panhypopituitarism, optic hypoplasia associated with visual impairment and symptomatic seizures. We believe that this case illustrates the need for caution in interpreting the significance of subtle midline intracranial abnormalities in the fetal brain, particularly when there is an aberration in development of the septum pellucidum. It has been well documented that visualization of the cavum septi pellucidi is a reliable means of confirming integrity of midline intracranial anatomy on screening ultrasound examination2. However, the septum pellucidum itself has not been well characterized histopathologically during fetal life, and pathogenesis in development is not well understood3. A hypothetical etiological association between septal agenesis and other midline brain anomalies has been postulated4. This is ascribed to possible vascular incidents which would explain the associated findings in embryologically disparate events. It could be extrapolated that an anomaly involving midline brain development, specifically development of the septum pellucidum, could be associated with other midline brain abnormalities. This case illustrates the importance of awareness of the possibility of pituitary and chiasmatic abnormalities, which may be difficult to detect with antenatal imaging and may result in significant clinical neonatal morbidity and developmental disability. D. Pugash*†, S. Langlois‡, P. Power§ and M. Demos¶ †Radiology, University of British Columbia, Ultrasound 1 T48, BC Women's Hospital, 4500 Oak St., Vancouver, British Columbia V6H 3 N1, Canada; ‡Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; §Medical Genetics, British Columbia Women's Hospital, Vancouver, British Columbia, Canada; ¶Pediatrics and Neurology, University of British Columbia, Vancouver, British Columbia, Canada *Correspondence. (e-mail: dpugash@cw.bc.ca)