Institution: | 1. Grupo de Enfermedades Raras, Mitocondriales y Neuromusculares (ERMN), Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain;2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain;3. Unidad Pediátrica de Enfermedades Raras, Enfermedades Mitocondriales y Metabólicas Hereditarias, Hospital 12 de Octubre, Madrid, Spain;4. Servicio de Radiología, Sección de Neurorradiología, Hospital 12 de Octubre, Madrid, Spain;5. https://orcid.org/0000-0001-6250-7745;6. Francisco Martínez‐Azorín, Grupo de Enfermedades Raras, Mitocondriales y Neuromusculares (ERMN), Instituto de Investigación Hospital 12 de Octubre (i+12), Centro de Actividades Ambulatorias (CAA), 6a Planta, Bloque E, Avda. Córdoba s/n, E‐28041 Madrid, Spain. |
Abstract: | We report the case of a Caucasian Spanish origin female who showed severe psychomotor developmental delay, hypotonia, strabismus, epilepsy, short stature, and poor verbal language development. Brain magnetic resonance imaging scans showed thickened corpus callosum, cortical malformations, and dilated and abnormal configuration of the lateral ventricles without hydrocephalus. Whole‐exome sequence uncovered a de novo variant in the microtubule associated serine/threonine kinase 1 gene (MAST1; NM_014975.3:c.1565G>A:p.(Gly522Glu)) that encodes for the MAST1. Only 12 patients have been identified worldwide with 10 different variants in this gene: six patients with mega‐corpus‐callosum syndrome with cerebellar hypoplasia and cortical malformations; two patients with microcephaly and cerebellar hypoplasia; two patients with autism, one patient with diplegia, and one patient with microcephaly and dysmorphism. Our patient shows a new phenotypic subtype defined by mega‐corpus‐callosum syndrome with cortical malformations without cerebellar hypoplasia. In conclusion, our data expand the phenotypic spectrum associated to MAST1 gene variants. |