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Today, whole-genome array technologies allow to perform high-resolution breakpoint mapping and to rule out complex imbalances. fluorescence in situ hybridization (FISH). Until the year 2000, the technical options to establish a genotype-phenotype correlation were limited to targeted analyses and methods of restricted resolution, e.g. The minimum extent of this Down Syndrome Critical Region (DSCR), however, has been a matter of discussion. revealed that the genes which are essential in producing the main DS features cluster within a relatively small region in chromosomal bands 21q22.2q22.3. Particularly genotype-phenotype studies on partial trisomies performed by Sinet et al. It has been known for decades that not the complete duplicated chromosomal region in trisomy 21 patients contributes equally to the DS phenotype. DS is acknowledged as a gene dosage disease where overexpression of genes located on chromosome 21 distorts the balance of gene products. 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.ĭown syndrome (DS), typically caused by complete trisomy 21, is associated with a wide range of clinical phenotypes including cognitive deficits, craniofacial dysmorphism, neurological, cardiovascular, immunological defects as well as ophthalmologic and hearing problems. This presents one of the smallest duplications within DSCR leading to a Down syndrome phenotype. Array-CGH analysis confirmed a 2.56 Mb duplication of chromosome 21q22.13q22.2 encompassing DYRK1A. Conventional karyotype was normal, whereas interphase FISH analysis revealed three signals for DSCR in approximately 40% of lymphocytes and 80% of buccal mucosa cells. 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. However, patients with small duplications of DSCR without accompanying deletions have rarely been reported. Down syndrome, typically caused by trisomy 21, may also be associated by duplications of the Down syndrome critical region (DSCR) on chromosome 21q22.