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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?
  • Andrea Praticò,
  • Federica Sullo,
  • Martino Ruggieri
Andrea Praticò
University of Catania
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Federica Sullo
University of Catania
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Martino Ruggieri
University of Catania
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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.