Microdeletions and microduplications are recurrent in the q11.2 region of chromosome 22. The 22q11.2 duplication syndrome is an extremely variable disorder with a phenotype ranging from severe intellectual disability, facial dysmorphism, heart defects, and urogenital abnormalities to very mild symptoms. Both benign and malignant hematological entities are rare. A male patient was diagnosed with mild facial dysmorphia, congenital heart anomalies shortly after birth and acute bowel obstruction due to malrotation of the intestine at the age of 3 years. A whole-genome single nucleotide polymorphism (SNP) array revealed a de novo 6.6 Mb duplication in the 22q11.1q11.22 chromosomal region. A year later, the patient was diagnosed with acute pre-B lymphoblastic leukemia (pre-B ALL). Five genes, CDC45, CLTCL1, DGCR2, GP1BB and SEPT5, in the 22q11.1q11.22 region are potentially responsible for cell cycle division. We hypothesized that dosage imbalance of genes implicated in the rearrangement could have disrupted the balance between cell growth and differentiation and played a role in the initiation of malignancy with a hyperdiploid leukemic clone, whereas over-expression of the TBX1 gene might have been responsible for congenital heart defects and mild facial dysmorphia.
Keywords: 22q11.1q11.22 duplication; Congenital heart defect; Facial dysmorphia; Leukemia; Leukemogensis; Malrotation of the intestine; TBX1 gene.