Introduction
Aicardi Syndrome (AS) [OMIM #304050] is a rare and severe neurodevelopment disorder characterized by agenesis/hypogenesis of the corpus callosum, ocular abnormalities and spasms in flexion (Young et al, 2016). It was named after Jean Aicardì, who first described this nosological entity in 1965 (Aicardi et al, 1965); after his original report, other findings have been included within the spectrum of the syndrome: a nearly exclusive involvement of the female gender, chorioretinal lacunae, costovertebral anomalies (Aicardi, 2005) as well as other brain malformations (i.e. polymicrogyria, periventricular and subcortical heterotopia, intracranial cysts, cerebellar abnormalities, and enlarged cisterna magna) (Lund et al, 2015). Facial dysmorphisms may be absent or subtle and only microphtalmia, prominent premaxilla with upturned nasal tip and sparse lateral eyebrows have been recognized among the “supporting features” for a diagnosis; by the contrary, a severe, drug-resistant epilepsy is often present, together with some non-specific EEG findings including hemispheres asynchrony, hypsarrhytmia, burst suppression (Nascimento et al, 2016). Cognition is usually severely affected and a global intellectual disability reported in almost all patients (Grosso et al, 2007) ( Tuft et al, 2017).
AS has never been reported as inherited and no familial cases can be found in literature; a unique genetic cause for this syndrome has never been discovered. It is known that affected individuals are always female or 47,XXY males, and it has been thought, for this reason, that ade novo dominant mutation on the X-chromosome may be the (most important) cause of the disease, with a hemizygous lethality in males (Aicardi, 2005).
We herein report on a female patient, affected by AS and presenting the classic triad (anomaly of the corpus callosum, choriorentinal lacunae, drug-resistant epilepsy), other severe brain abnormalities (i.e. polymicrogyria, cortical dysplasia, heterotopias and asymmetric ventricles) and psychomotor delay. Submitted to a NGS analysis of 286 genes associated to epilepsy and brain malformations, a compound heterozygosis (in trans) of DCHS1 variants was found. As this gene has been related to many cerebral malformation anomalies, together with a distinct syndrome (i.e. Van Maldergem syndrome, OMIM #601390) we assume that the phenotype of this AS patient may be caused by her gene variants and that the two syndromes may share some genetic factors in their pathogenesis. Moreover, DCHS1 location is close to TEAD1 , a gene reported as causative of AS: beside the other possible explanations of our findings (i.e. an incidental finding, or a new subtype of Van Maldergem Syndrome) it would be possible that an imbalance in the genetic region (11p15) containing DCHS1 andTEAD1 could have a critical role in the pathogenesis of AS.
A written informed consent has been obtained by the patient’s parents in order to report her clinical case.