Aicardi syndrome: Unique baby, unique condition

The first patient, a 3-month-old girl baby presented with recurrent episodes of abnormal tonic posturing, frothing, and abnormal blinking of eyes since the 22nd day of her life. Clinical examination demonstrated abnormal facial morphological features like prominent premaxilla and sparse lateral eyebrows.

The second patient, a 6-month-old girl baby with recent abnormal body movements, whose antenatal ultrasound scan demonstrated an interhemispheric cystic lesion in the brain with corpus callosum agenesis. Clinical examination demonstrated mild scoliosis and cleft lip.

The non-contrast brain MRI examination was performed on a 3T MRI with spin-echo T1, T2, and FLAIR sequences in all 3 orthogonal planes. Imaging findings demonstrated a constellation of classic findings that pointed toward a neurodevelopmental pathology. The first baby had an additional MRI finding of polymicrogyria (Figure 1b). On the other hand, the second baby had an additional finding of a posterior ocular coloboma on the left side (Figure 2b). Both the patients shared common MRI findings like complete corpus callosum agenesis (Figures 1a, 2a and 2c), uni/bi-lobulated interhemispheric cyst (Figures 1a, 1b and 2a), and sub-ependymal/sub-cortical grey matter heterotopia (Figures 1b, 2a and 2c). Both patients shared a similar spectrum of imaging findings; however, they differed slightly when it came to the clinical presentation and examination.

Background

Aicardi syndrome (AS) was first described by Jean Dennis Aicardi, as an X-linked syndrome presenting as a triad of infantile spasms, partial or total agenesis of the corpus callosum, and various ocular abnormalities [1,9]. The exact pathophysiology for this syndrome still remains a mystery, with exome sequencing failing to identify the exact genetic cause of AS [2]. Clinical trials are underway to understand the causative chromosomal abnormality better.

Clinical Perspective

Patients commonly present with neurodevelopmental delay and infantile spasms. Further studies have found that it can also be associated with microcephaly, microphthalmia, hemivertebrae, cleft lip, and palate, among others [3].

Imaging Perspective

Most common MRI findings involve partial or total corpus callosum agenesis, interhemispheric cyst, heterotopia, and polymicrogyria. Other less common features include microphthalmia, posterior retrobulbar ocular colobomatous cysts, and abnormal myelination patterns. There was no clear consensus on the diagnostic criteria for AS. In 2005, Sutton et al proposed a modified diagnostic criteria:

• Major features are cortical malformations (polymicrogyria), periventricular and sub-cortical heterotopia, cysts around the third ventricle and/or choroid plexus, and optic disc/nerve coloboma. The supporting features are a prominent premaxilla with an upturned nasal tip and sparse lateral eyebrows, vascular malformations/malignancy, vertebral and costal abnormalities, microphthalmia, split-brain EEG, and gross cerebral hemispheric asymmetry [4,8,9]. The presence of two classic features, along with the other two features, is strongly indicative of Aicardi syndrome [4].

Outcome

Aicardi syndrome has no cure, and the treatment mainly revolves around symptomatic management. With seizures being a predominant issue plaguing the individuals affected by this syndrome, anticonvulsants are widely used in the treatment. Epilepsy is the most difficult aspect, if not impossible, to treat. Multiple musculoskeletal anomalies are another common feature of AS, which makes physiotherapy and orthopaedic surveillance an important treatment option for affected individuals [5]. Gastrointestinal problems like constipation, reflux, and diarrhoea were reported as the second most common health problem after seizures, and various methods were employed to tackle them [2]. Pulmonary complications are the most common cause of death; therefore, any infections should be dealt with aggressive use of antibiotics [1]. Pulmonary infections are presumed to be secondary to hypotonia [10]. A study found that the risk of death in affected individuals reduces from the first year of life until the age of 4. Thereafter, it continuously increases until the age of 16, after which it drops again [6].

Take Home Message / Teaching Points

MRI plays a pivotal role in the early detection and diagnosis of Aicardi syndrome when correlated with the clinical examination of the patient. The higher life expectancy in people with AS hints at a higher functioning capacity. Therefore, parents should be counselled and motivated to promote and support the cognitive development of their children affected by Aicardi syndrome [1,6].

All patient data have been completely anonymised throughout the entire manuscript and related files.