Refractory infantile spasms associated with mosaic variegated aneuploidy syndrome

Area of Science:

• Genetics
• Oncology
• Neurology

Background:

• Mosaic variegated aneuploidy syndrome (MVAS), also known as premature chromatid separation syndrome, is a rare autosomal recessive disorder linked to BUB1B gene mutations.
• It is characterized by a high risk of malignancy, including rhabdomyosarcoma, Wilms tumor, and leukemia.
• Clinical manifestations include prenatal growth retardation, microcephaly, dysmorphism, feeding difficulties, hypotonia, seizures, and developmental delay.

Purpose of the Study:

• To report a case of MVAS with significant developmental brain anomalies and early-onset epileptic encephalopathy.
• To highlight the association between MVAS and neurological complications.
• To emphasize the importance of recognizing MVAS for diagnosis and genetic counseling.

Main Methods:

• A case study of a male infant with severe developmental delay, microcephaly, hypotonia, and intractable seizures.
• Magnetic resonance imaging revealed Dandy-Walker malformation.
• Chromosomal analysis confirmed mosaic variegated aneuploidy with premature chromatid separation.

Main Results:

• The patient presented with refractory infantile spasms and hypsarrhythmia.
• Wilms tumor and an intraorbital tumor were diagnosed at 22 months.
• Chromosomal analysis revealed mosaic variegated aneuploidy in 59.5% of cells, with premature chromatid separation observed across all chromosomes.

Conclusions:

• Mosaic variegated aneuploidy syndrome can be associated with developmental brain anomalies causing early-onset epileptic encephalopathy.
• Increased awareness of MVAS is vital for accurate diagnosis and appropriate genetic counseling.
• This case underscores the complex clinical spectrum of MVAS, extending to severe neurological impairments.