Case Reports

Indian Pediatrics 2000;37:542-545

From the Departments of Pediatrics and Radiodiagnosis*, Safdarjang Hospital, New Delhi 110 029, India.

Reprint requests: Dr. K.C. Aggarwal, Senior Pediatrician, Department of Pediatrics, Safdarjang Hospital, New Delhi 110 029, India.

Manuscript Received: August 23, 1999;
Initial review completed: September 27, 1999;
Revision Accepted: November 19, 1999

In 1965, Aicardi and colleagues reported a new syndrome characterized by agenesis of corpus callosum (ACC) with cortical heterotopia, infantile spasm, chorioretinopathy, mental retardation with or without associated vertebral anomalies. Amongst these, ACC, infantile spasms, mental retardation and chorioretinal lacunae are the constant findings(1). It is a rare neuro-ophthalmic disorder with progressive mental deterioration. All the patients described till date have been females except two male subjects(2,3). We describe a male baby who had all the essential features suggestive of Aicardi’s Syndrome along with ventricular septal defect and lissencephaly.

A 9-month-old male child, first in birth order was a product of full term normal vaginal delivery with normal perinatal period. No history of consanguinity was noted. The child presented to us with delayed milestones, recurrent recalcitrant infantile spasms, inability to recognize his mother and history suggestive of recurrent chest infections (poor feeding and fever with fast respiration). No family member was affected with a similar illness and there was no history suggestive of intrauterine infection in the antenatal period.

On examination, there was microcephaly with head circumference of 37 cm (less than –3 SD). There was no evidence of cranio-synostosis or neurocutaneous malformation. The cardiovascular examination revealed Grade III ejection systolic murmur best heard at left parasternal border, flow middiastolic rumble and S3 at the apex. P2 was loud with normal split. Chest examination revealed tachypnea with subcostal retractions and basal crepita-tions. Central nervous system examination showed a hypotonic child with brisk deep tendon jerks with extensor plantars. Head control was partial with some head lag. The child responded to sound. Vision was doubtful with left side micro-opthalmia. The fundus examination, done under general anesthesia revealed bilateral chorioretinal lacunae, which were more prominent on the right side. No evidence of chorioretinitis was noted. There was no hepatosplenomegaly.

Investigations revealed cardiomegaly with increased pulmonary vascularity on X-ray chest. Electrocardiogram revealed left ventricular preponderance with normal QRS axis and tachycardia. Color Doppler Echocardiography confirmed moderate to large subaortic VSD with pulmonary blood flow more than 2:1. EEG showed diffuse background slowing with asynchronous burst-suppression pattern. Brain stem auditory evoked responses were normal. Visually evoked potential showed abnormal record. Investigation for TORCH group of infections was negative. X-ray skull did not show any calcification. CT scan head showed agenesis of corpus callosum with bat-wing anomaly with lissencephaly, i.e., smooth surface of cerebral cortex with absence of gyri and sulci (Figs. 1&2). MRI confirmed the CT head findings and also showed heterotopia with migration defect. Skeletal survey of baby did not reveal any abnormality except mild thoracic scoliosis.

In the present case all the essential features suggestive of Aicardi’s Syndrome, i.e., infantile spasms with agenesis of corpus callosum, chorioretinal lacunae and micro-ophthalmia were present. No other skeletal anomaly was detected except thoracic scoliosis.

Since the first case description, only two males with this disorder have been reported earlier(2,3). Karyotyping is not recommended routinely in this condition. However, because of phenotypic male sex, it was performed in this patient. The karyotype was 46 xy but mosaicism can not be excluded.

Isolated agenesis of corpus callosum (ACC) can be a chance finding on CT Scan head. Majority of them remain asymptomatic throughout childhood. Many syndromes have been documented with ACC but the most widely described one is Aicardi’s syndrome in which ACC is associated with neuronal migration defect in the cerebral cortex, especially in periventricular area. In addition to this, polymicrogyria and neuronal heterotopia may also be associated. Lissen-cephaly, i.e., smooth surfacing of cerebral cortex with absence of sulci and gyri has not been described in Aicardi’s syndrome earlier and is another unusual feature in this case. A close differential diagnosis is Walker Waburg syndrome (WWS) which is comprised by lissencephaly (type 11), microophthalmia, retinal dysplasia and hypotonia. The described case does not fit into WWS as there is no absence of cerebellar vermis, there is extreme type of lissencephaly (type 1) and ACC is present. Miller Dicker syndrome, which is also associated with lissencephaly and heart defect can be excluded by the presence of retinal changes and ACC(4).

Fig. 1. CT scan head, axial cut at high parietal level shows absence of gyri and sulci in the cerebral cortex suggestive of lissencephaly and Bat-Wing appearance of lateral ventricles suggestive of agenesis of corpus-callosum.

Fig. 2. CT scan head axial cut at ventricle level shows wide separation of anterior horn of lateral ventricles with high position of third ventricle suggestive of agenesis of corpus collasum. There is smooth surface of cerebral cortex suggestive of lissencephaly.

The abnormal event in Aicardi’s syndrome probably supervenes in fourth to fifth week of gestation(5). A viral cause has also been suggested but not substantiated by others(6). A genetic theory has been advocated after studying a pedigree of eighteen cases of Aicardi’s Syndrome. It is postulated to be a sex linked dominant inheritance with early embryonic lethality in hemizygous males with all cases being new mutation. Some authors believe that the abnormal gene is located at the XP-22.3 locus(5,6). Eye-findings in Aicardi’s Syndrome consist of chorioretinal lacunae in posterior pole of eye with ectopic pigmented epithelium. There is micro-cornea with micro-ophthalmia along with hypoplasia of optic nerve and macula(6-8). Conspicuously there is absence of chorioretinitis. Various skeletal anomalies described are absent ribs, hemivertebra, kyphoscoliosis and fusion of vertebrae. Unilateral cerebellar hypoplasia has also been described in Aicardi’s Syndrome(9). Aicardi’s syndrome is a rare neuro-ophthalmic disorder, which carries a bad prognosis because of poorly controlled seizures and mental retardation. Majority die of aspiration pneumonitis. The atypical features in the case described by us include male sex, ventricular septal defect and type I lissen-cephaly, which has not been reported earlier.

1. Aicardi J, Lefebre J, Letique Koechlin A. Spasm in flexion, callosal agenesis, ocular abnormali-ties: A new syndrome. Electrocephalog Clin Neurophysiol 1965; 19: 607-610.

2. Curatolo P, Libutti G, Dallapiccula B. Aicardi syndrome in a male infant. J Pediatr 1980; 96: 286-287.

3. Hopkin J, Humphery I, Keith CG. The Aicardi syndrome in 47/xxy male. Aust Pediatr J 1979; 15: 278-280.

4. Nurille GR. Pediatric Neurology. In: Brain’s Diseases of Neurology, 10th edn. Ed. Walton J. London, Oxford University Press, 1993; pp 464-465.

5. Donnenfield AE, Packer RJ, Zackai EH. Clinical, cytogenetics and pedigree findings in 18 cases of Aicardi’s Syndrome. Am J Med Genet 1989; 32: 461-467.

6. Allaire GS, Michaud J, Polomeno RC, Dube J. Aicardi’s Syndrome: A clinico-pathological report. Can J Ophthalmol 1995; 30: 154-158.

7. Orquin J. Syndrome of Aicardi. J Ophthalmol 1981; 16: 200-202.

8. Host GH, Billion F, Ouvrier R. Ocular features of Aicardi’s Syndrome. Arch Ophthalmol 1978; 96: 291-295.

9. Gonzalez CS, Prats Vinas JM. Unilateral aplasia of cerebellumin Aicardi’s Syndrome. Neuro-logia 1998; 13: 254-256.