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.