Mild phenotype of a de novo partial trisomy 13q22.2-qter: case report and review of the literature

Large duplications or triplications involving the 13q22-qter chromosomal region have been reported to be associated with seizures in some patients. Herein, we report an additional case of epilepsy linked to a trisomy 13q22.2-qter and provide a detailed summary of the associated clinical and magnetic resonance imaging (MRI) findings. Whole-genome sequencing was performed on the patient. Sequencing data, including whole-exome sequencing (WES), copy number variation (CNV) sequencing, and mitochondrial genome sequencing, were used to identify the genetic basis of the disease. The patient experienced her first febrile seizure at the age of 14 months. Seizure semiology evolved from initial febrile generalized tonic-clonic seizures to later afebrile focal to bilateral tonic-clonic seizures. Cranial MRI revealed white matter hyperintensities in bilateral lesions, predominantly in posterior regions. Follow-up MRI at 2 years of age revealed mild progression in the extent of T2-FLAIR hyperintensities compared to the initial scan at 8 months of age, suggesting a slowly progressive white matter abnormality. Interictal EEG showed multifocal sharp waves. Her motor development is normal, while her language ability is somewhat limited with a relatively small verbal vocabulary. CNV-sequencing analysis identified a de novo heterozygous duplication in the region of 13q22.2-qter. Long-term biochemical follow-up showed persistent mild elevations in creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and transient elevations in total bile acid (TBA). The presented case illustrates the phenotype of 13q22.2-qter and reaffirms the importance of studying the karyotype of any patient with seizures who exhibit special clinical features, including developmental disorders, malformations, and leukoencephalopathy. The range of chromosomal duplication and the second chromosomal abnormality potentially explain the mechanism of phenotypic variation.