Refractory infantile spasms associated with mosaic variegated aneuploidy syndrome

Background: Mosaic variegated aneuploidy syndrome (Online Mendelian Inheritance in Man 257300), or premature chromatid separation syndrome, is a rare cancer-prone disorder associated with an autosomal recessive trait related to BUB1B gene mutations. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor, and leukemia reported in several cases. Clinical features also include prenatal-onset growth retardation, microcephaly, mild dysmorphism, feeding difficulty, hypotonia, seizures, and developmental delay.

Patient: A boy patient exhibited severe developmental delay, microcephaly, hypotonia, intractable seizures including infantile spasms with hypsarrhythmia at 6 months old, and Dandy-Walker malformation on magnetic resonance imaging. Seizures were refractory to conventional antiepileptics and treatment with adrenocorticotropic hormone. Wilms tumor and an unidentified intraorbital tumor also developed at 22 months old.

Results: Chromosomal analysis showed multiple aneuploid cells, and premature chromatid separation was found in all chromosomes in 59.5% of 119 cells, indicating mosaic variegated aneuploidy syndrome.

Conclusions: The present case report demonstrates that mosaic variegated aneuploidy syndrome can be associated with developmental brain anomalies that lead to early-onset epileptic encephalopathy. Awareness of this disorder is important not only for proper diagnosis but also for genetic counseling of the family.