Down syndrome phenotype in a boy with a mosaic microduplication of chromosome 21q22

Background: Down syndrome, typically caused by trisomy 21, may also be associated by duplications of the Down syndrome critical region (DSCR) on chromosome 21q22. However, patients with small duplications of DSCR without accompanying deletions have rarely been reported.

Case presentation: Here we report a 5½-year-old boy with clinical features of Down syndrome including distinct craniofacial dysmorphism and sandal gaps as well as developmental delay. Conventional karyotype was normal, whereas interphase FISH analysis revealed three signals for DSCR in approximately 40% of lymphocytes and 80% of buccal mucosa cells. Array-CGH analysis confirmed a 2.56 Mb duplication of chromosome 21q22.13q22.2 encompassing DYRK1A.

Conclusion: This presents one of the smallest duplications within DSCR leading to a Down syndrome phenotype. Since the dosage sensitive gene DYRK1A is the only duplicated candidate DSCR gene in our patient, this finding supports the hypothesis that DYRK1A contributes to dysmorphic and intellectual features of Down syndrome even in a mosaic state.