Improving the phenotype description of Basel-Vanagaite-Smirin-Yosef syndrome, MED25-related: polymicrogyria as a distinctive neuroradiological finding

• DOI: 10.1007/s10048-020-00625-2
• Publication Date: 2020-08-20T07:04:22Z
• Authors: Ilenia Maini; Edoardo Errichiello; Stefano Giuseppe ...; Simonetta Rosato; Veronica Bizzarri; Marzia Pollazzon; Gabriele Trimarchi; Gianluca Contrò; Benedetta Cavirani; Chiara Gelmini; Manuela Napoli; Claudio Moratti; Rosario Pascarella; Susanna Rizzi; Carlo Fusco; Orsetta Zuffardi; Livia Garavelli
• Keywords: Male; Comparative Genomic Hybridization; 0303 health sciences; Mediator Complex; Developmental Disabilities; Intellectual disability; 610; Basel-Vanagaite-Smirin-Yosef syndrome; MED25; Neuropathy; Pedigree; 3. Good health; Malformations of Cortical Development; 03 medical and health sciences; Thin corpus callosum; Phenotype; Polymicrogyria; Intellectual Disability; Mutation; Multiple congenital anomalies; Humans; Abnormalities, Multiple; Female; Child

Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) is an extremely rare autosomal recessive genetic disorder caused by variants in the MED25 gene. It is characterized by severe developmental delay and variable craniofacial, neurological, ocular, and cardiac anomalies. Since 2015, through whole exome sequencing, 20 patients have been described with common clinical features and biallelic variants in MED25, leading to a better definition of the phenotype associated with BVSYS. We report two young sisters, born to consanguineous parents, presenting with intellectual disability, neurological findings, and dysmorphic features typical of BVSYS, and also with bilateral perisylvian polymicrogyria. The younger sister died at the age of 1 year without autoptic examination. Whole exome sequencing detected a homozygous frameshift variant in the MED25 gene: NM_030973.3:c.1778_1779delAG, p.(Gln593Argfs). This report further delineates the most common clinical features of BVSYS and points to polymicrogyria as a distinctive neuroradiological feature of this syndrome.