Agenesis of corpus callosum - a rare case.AK Desai, AG Bhide, SA Bhalerao
Nowrosjee Wadia Maternity Hospital, Parel, Mumbai, India., India
A case of corpus callosum agenesis associated with a chromosomal structural defect is described.
Keywords: Case Report, Chromosome Deletion, Chromosomes, Human, Pair 6, Corpus Callosum, abnormalities,Fatal Outcome, Female, Human, Infant, Newborn,
Corpus callosum is an important commissure, which connects the non-olfactory areas of the right and left hemispheres. It is developed from the telencephelon. It is essential for learning, discrimination, sensory experience, memory, synchronicity of sleep. It has been claimed that there are gender differences in the size and shape of the splenium of corpus callosum. A case of corpus callosum agenesis is described.
A 29-year-old lady married since three years (G2P0L0, 32 weeks' gestation) was referred from a private nursing home for intrauterine growth retardation (IUGR) and oligohydramnios.
Her first pregnancy was an intrauterine foetal demise at 26 weeks. She was fully investigated then and it was an unexplained death. On admission, uterus was clinically 28 weeks. Amniotic fluid seemed to be reduced. Fundal height was 24 cm. Foetal heart sounds were 150/min and regular. Ultrasonography (USG) showed single, live foetus in cephalic presentation. Composite gestational age was 28 weeks with symmetric IUGR present. Amniotic fluid index was 5 cm. Corpus callosum was absent. Cavum septum pellucidum was absent, third ventricle was displaced superiorly and dilated and the lateral ventricles were slightly dilated 12 mm. each. No other systemic or intracranial anomalies were seen. Doppler done showed normal uteroplacental flow.
The couple was offered cordocentesis for karyotyping however they did not agree. Patient was kept admitted with daily foetal kick count, non stress test twice weekly and biophysical profile weekly. At 35 weeks of gestation non-stress tests done were repeatedly non- reactive.
USG done then showed composite gestational age of 31 weeks, foetus in breech presentation. Estimated birth weight was 1.5 Kg. Amniotic fluid index was 4 cms, breathing movements were absent and foetal movements were sluggish.
The couple was explained the guarded prognosis of the baby, however they opted for an elective caesarean in view of a small for gestational age baby in breech presentation.
Elective caesarean was carried out and a 1.8 kg female baby delivered. Baby did not cry immediately after birth. APGAR at 5 minutes was 4/10. Baby was resuscitated and required continuous airway positive pressure ventilation. The baby had dysmorphic facies, high arched palate, hyper flexible joints, dislocation of hip joint, small second toe of both feet. Cranial ultrasound confirmed the antenatal findings. Cord blood was sent for karyotyping. Radiograph revealed defective body of eighth thoracic vertebra. No other skeletal abnormalities seen. The baby died of terminal cardio respiratory arrest four hours after birth. Karyotyping of the baby was 44 XX, terminal deletion of long arm of chromosome 6, q22- q terminal [Figure - 1]. Karyotyping of both parents was normal which suggested that the foetal chromosomal aberration was de-novo rather than as a result of a balanced translocation in one of the parents.
Corpus callosum is the largest cerebral commissure connecting neocortical areas and develops between 12 to 20 weeks of gestation. The development results from neocortical commissural axon fasciculation and reflects the inter-hemispheric circuitry and successive steps of synaptogenesis. It is a phylogenetically recent structure and not necessary for vital functions.
In agenesis of corpus callosum, commissural fibres do not cross the midline instead thick bundles of intersecting fibres called Probst bundles which lie along the super medial aspect of the lateral ventricles and the third ventricle may sometimes be displaced upward. In most cases there is a stable, non-progressive dilatation of the caudal portion of lateral ventricles.
There is a high incidence of agenesis of corpus callosum in aberrations of chromosomes 8,11, 13-15, 18 and rarely chromosome 6.
It has been associated with several syndromes such as Andermann Syndrome (peripheral neuropathy with corpus callosum agenesis). Aicardi Syndrome (infantile spasms, ocular anomalies and agenesis of corpus callosum), Shapiro's syndrome (paroxysmal hypothermia with agenesis of corpus callosum) and sporadically with Dandy Walker syndrome, foetal alcohol syndrome, Leigh's syndrome, Arnold Chiari II syndrome,.
The typical ultrasound features are absence of corpus callosum and cavum septum pellucidum, increased separation of the lateral ventricles. There is marked separation of the slit like horns of the lateral ventricles, dilatation of the occipital horns creating a typical 'rabbit's - ear' appearance and upward displacement of the third ventricle.
Despite the limitations of early diagnosis, the value of antenatal diagnosis is two-fold. Firstly as this condition is associated with a high incidence of other structural anomalies, a careful search of the entire foetal anatomy is required. The prognosis of cases with associated anomalies is very poor. Secondly, it is important to recognize that the sonographic appearance of agenesis of corpus callosum may be very similar to that of uncomplicated ventriculomegaly as the most striking finding is the enlargement of the occipital horns and atria.
The diagnosis if apparently isolated foetal agenesis of corpus callosum (in the absence of sonographically detectable anomalies) appears to carry an excellent prognosis with an 85% chance of normal developmental outcome and 15% risk of handicap in the form of seizures or other mental disorders. This is after excluding cases that died, had termination of pregnancy or where outcome was not reported. This is in keeping with the hypothesis that neurological impairment is not a consequence of the agenesis per se but rather of the many associated anomalies. Foetal karyotyping should be offered to all cases independent of other sonographically detectable anomalies.
Moreover, this diagnosis leads to concern regarding the possibility of an association with either genetic syndromes, inborn errors of metabolism or anatomic anomalies, which cannot be tested by prenatal karyotyping. Other factors, which may aid the prognosis have been reported. The upward displacement of the third ventricle and widened inter-hemispheric tissue are most frequently associated with neurological impairment, associated anomalies or both.
The precision of these estimations is low, but represent the best information available to prospective parents at the current time.
As isolated agenesis is compatible with normal intellectual development, this raises an important issue with regard to continuation of pregnancy and possible outcome. Each case should be dealt with a pleuridisciplinary approach, with appropriate prenatal counselling and management individualised.
[Figure - 1]