A patient with Aicardi syndrome phenotype and DCHS1 gene variants. A new
step in the pursuit of the genetic cause of the disease or an incidental
finding?
Abstract
Aicardi Syndrome (AS) is a rare and severe neurodevelopment disorder,
usually involving the female gender and characterized by hypogenesis of
the corpus callosum, ocular abnormalities (chorioretinal lacunae), a
severe, drug-resistant epilepsy, intellectual disability, costovertebral
anomalies, other brain malformations and mild facial dysmorphism. The
genetic cause of AS has never been found. We report on a female patient,
affected by AS spectrum and presenting the classic triad (hypogenesia of
the corpus callosum, choriorentinal lacunae, drug-resistant epilepsy)
and other brain malformations (polymicrogyria, cortical dysplasia,
heterotopias and asymmetric ventricles). A NGS-panel for epilepsy and
brain malformations disclosed a compound heterozygosis in DCHS1 gene,
which is the cause of Van Maldergem syndrome, characterized by severe
face dysmorphism, skeletal abnormalities, respiratory tract
malformations and severe brain involvement. We hypothesize that the
phenotype of this AS patient may be caused by variants in DCHS1 gene and
that the two syndromes may share common genetic causes. Interestingly,
DCHS1 is located in proximity to TEAD1 (chromosome 11p15), reported as
causative of AS in a single patient, and both the proteins are involved
in the hippo-pathway (which regulates cellular growth and apoptosis).
Alternatively, the patient could present a new subtype of Van Maldergem
Syndrome, without face dysmorphism and skeletal abnormalities.