Identification of a Novel Variant in the MAD1L1 Gene in an Individual with Mosaic Variegated Aneuploidy Syndrome (MVAS)

• Mosaic Variegated Aneuploidy Syndrome (MVAS) is a rare autosomal recessive disorder characterized by mosaic aneuploidy, chromosomal instability, developmental delays, congenital anomalies, and cancer predisposition.
• Variants in MVAS-related genes lead to defects in the spindle assembly checkpoint, a key mechanism that ensures chromosomes are correctly distributed to daughter cells during mitosis.
• Given the high cancer risk associated with MVAS, long-term follow-up, genetic counseling for family members, and ongoing surveillance are essential for patient care and risk assessment.
• The proband was a 6-year-old male with a prior history of right-sided Wilms tumor status post resection, chemotherapy, and bone marrow transplant who was evaluated at the genetic clinic due to global developmental delay, hyperpigmented macules, thrombocytopenia, and concerns for myelodysplastic disease. He was diagnosed with acute myeloid leukemia after genetic diagnosis.
• There was no significant family history that pertained to the patient’s phenotype, though this patient’s parents are reportedly consanguineous.
• Objective: To identify and characterize a novel MAD1L1 variant in a patient with MVAS.