Prenatal diagnosis of colpocephaly with absent corpus callosum

Introduction

Colpocephaly is a congenital abnormality in the ventricular system of the brain and often associated with partial or full agenesis of the corpus callosum.^1,2 It is a rare form of foetal ventriculomegaly and must be differentiated from the more common causes such as loss of brain volume (perhaps due to infection or infarction), or impaired outflow or absorption of cerebrospinal fluid from the ventricles. Herein, we report a case of colpocephaly with absent corpus callosum, confirmed antenatally with foetal MRI following diagnostic suspicion based on mild lateral ventriculomegaly and absent septum pellucidum at prenatal sonography. Prenatal diagnosis of central nervous system (CNS) anomalies and possible associated abnormalities are vital for providing correct information to parents regarding the neurological development of their child and pregnancy management.

Case presentation

A male, preterm 32 weeks gestation baby was born to healthy nonconsanguineous parents by emergency section following nonreassuring cardiotocography (CTG) after the onset of preterm labour. Mother was 33 years old and had one previous child born at term; the baby was small for gestational age but otherwise healthy. She was smoking throughout her pregnancy and reports no exposure to teratogens. There was no family history of birth defects and neurologic or cognitive impairment. Her pregnancy was unremarkable and anomaly scan at 20 weeks was normal. However follow-up sonogram done at 28 weeks as previous baby being small for date revealed mild lateral ventriculomegaly, absent septum pellucidum and corpus callosum could not be visualised. Foetal MRI done at 31 weeks confirmed agenesis of corpus callosum with colpocephalic ventricular prominence (Figures 1 and 2). Parents were counselled regarding the diagnosis and the need for postnatal evaluation and follow-up. OPEN IN VIEWER

OPEN IN VIEWER

Figure 2.

Coronal section of the foetal brain MRI at the level of third ventricle showing absence of corpus callosum.

Infant was intubated soon after birth in view of poor respiratory effort and required ventilatory support for 24 h. Apgars were 6 at 1 and 8 at 5 min. Clinical examination was essentially normal with no obvious dysmorphism. Birth weight (2025 g, 75th centile) and occipitofrontal circumference (31 cm, 75th centile) were appropriate for gestational age.

Investigation

Postnatal imaging, cranial ultrasound scans and MRI brain showed appearances consistent with absent corpus callosum and colpocephaly, but could have lead to the diagnosis of hydrocephalus if diagnosis was not known (Figures 3–6).Chromosomal analysis was normal and blood serology for toxoplasmosis, rubella, cytomegalovirus and herpes was negative. He was discharged from the neonatal unit on day 23 and his hearing screen and eye examinations were normal upon discharge. OPEN IN VIEWER

OPEN IN VIEWER

Figure 4.

Midline sagittal section of MRI brain showing complete absence of corpus callosum and highly placed third ventricle.

OPEN IN VIEWER

Figure 5.

Left parasagittal section of the brain MRI showing enlarged occipital horn of the lateral ventricle.

OPEN IN VIEWER

Figure 6.

Axial section of the brain MRI showing bilateral enlargement and parallel orientation of occipital horns of the lateral ventricles.

Follow-up

On follow-up, at corrected age of 22 months, his gross motor, fine motor skills, vision and social skills are age appropriate and his head circumference is normal. His parents have some concerns regarding his speech and he has been referred to audiology in view of this.

Discussion

The term colpocephaly is defined as disproportionate enlargement of the occipital horns of the lateral ventricles when compared with the frontal horns. The term was coined by Yakovlev and Wadsworth from the Greek word kolpos meaning hollow. ¹

Colpocephaly was later defined as persistence of the primitive foetal configuration beyond six months of gestational age.^2,3 Thus, when mild disproportionate enlargement of the occipital horns is seen prenatally and the ventricles appear otherwise normal, the use of the term colpocephaly is probably incorrect and some authors have termed the above as primitive foetal ventricular configuration. This is a relatively common MRI finding in 7% of normal population. Only when the disproportion was marked, or when the frontal horns have abnormal orientation, they used the term colpocephaly. ⁴ In our case, the diagnosis of colpocephaly was supported by typical appearances on prenatal imaging at 31weeks and postnatally with associated parallel orientation of lateral ventricles, highly placed third ventricle and absence of corpus callosum. Only when foetuses were determined to have colpocephaly rather than primitive foetal ventricular configuration, was complete or partial agenesis of corpus callosum found to be associated. ⁴

Colpocephaly may be associated with several other central nervous system malformation: agenesis of corpus callosum, neuronal migration disorders (lissencephaly, pachygyria), schizencephaly, microgyria, macrogyria, enlargement of cistern magna, cerebellar atrophy, optic nerve hypoplasia, chorioretinal coloboma, microcephaly, meningomyelocele and hydrocephalus.^1,2 Agenesis of corpus callosum is the most frequently associated malformation. ² The present case exemplifies this.

Colpocephaly is a disorder of multiple and diverse aetiologies, including (1) chromosomal anomalies such as trisomy-8 mosaicism and trisomy-9 mosaicism; (2) intrauterine infection such as toxoplasmosis; (3) perinatal anoxic ischaemic encephalopathy; (4) maternal drug ingestion during early pregnancy such as corticosteroids, salbutamol and theophylline, (5) familial or genetic origin with an autosomal or X-linked recessive inheritance and (6) periventricular leukomalacia due to the destruction of the white matter of the occipital lobe.^3,5 All investigations done in our case for the aetiology were unremarkable and there was no evidence of calcification, focal lesion or periventricular leukomalacia in MRI brain.

Prenatal diagnosis of CNS anomalies and possible associated abnormalities are vital for providing correct information to parents regarding the neurological development of their child and pregnancy management. For this reason, evaluation of the size of the lateral ventricles should be an integral part of the ultrasound examination in the second and third trimester. ⁶ The finding of cerebral ventriculomegaly should raise a suspicion of corpus callosum agenesis. Prenatal ultrasonography performed during the second trimester of pregnancy (<22 weeks) may not visualise the corpus callosum.^4,7,8 Therefore, diagnostic suspicion is based on indirect signs, such as absence of cavum septum pellucidum and/or an abnormal configuration of the lateral ventricles, such as in our case.^4,9 When ventriculomegaly is mild, i.e. with transverse diameter at the level of the atrium of 10–15 mm,^4,10,11 which accounts for some 15–20% of foetal ventriculomegaly, the risk of isolated agenesis of corpus callosum is 10% and that for corpus callosal agenesis with CNS or extra CNS malformations is 3%. ¹² In our case, the atrial diameter was 14–15 mm which prompted us to search for associated abnormalities and showed absent cavum septum pellucidum with absent corpus callosum. Subsequently foetal MRI, postnatal cranial scans and MRI brain showed appearances consistent with absent corpus callosum and colpocephaly with a highly placed third ventricle.

In conclusion, the diagnosis of colpocephaly should be considered in a developing foetus with ventriculomegaly disproportionately affecting the occipital horns and must be differentiated from the more common forms of foetal ventriculomegaly such as loss of brain volume (perhaps due to infection or infarction), or impaired outflow or absorption of cerebrospinal fluid from the ventricles. Visualisation of the entire lateral ventricles and searching for associated intracranial anomalies in cases of mild ventriculomegaly may help in identification of colpocephaly. Prenatal diagnosis of colpocepahly or corpus callosal agenesis is difficult with ultrasound and need prompt referral for foetal MRI scan and subsequent appropriate postnatal imaging as evidenced in previous reports and the present case.

Learning points

Colpocephaly is described as persistence of the primitive foetal configuration beyond six months of gestational age. Agenesis of corpus callosum is the most frequently associated malformation.