A 4.3Mb duplication of chromosome 21 bands q22.13 to q22.2 was diagnosed by interphase Fluorescent In-Situ Hybridisation (FISH) in a 31 week baby with cystic hygroma and hydrops; the duplication was later found in the mother and her 8 year old daughter by the same method and confirmed by array comparative genomic hybridization (aCGH). All had the facial gestalt of Down syndrome. This is the smallest accurately defined duplication of chromosome 21 reported with a Down syndrome (DS) phenotype. The duplication encompasses the gene DYRK1 but neither DSCR1 nor DSCAM, all of which have previously been implicated in the causation of DS. Previous karyotype analysis and telomere screening of the mother, and karyotype analysis and metaphase FISH of a Chorionic Villus Sample had all failed to reveal the duplication. The findings in this family add to the identification and delineation of a ‘critical region’ for the DS phenotype on chromosome 21. Cryptic chromosomal abnormalities can be missed on a routine karyotype for investigation of abnormal prenatal ultrasound findings, lending support to the use of aCGH analysis in this setting.
- Array comparative genomic hybridization
- Down syndrome critical region
- cystic hygroma