microdeletion syndrome
A microdeletion syndrome is a disorder caused by the loss of a chromosome piece too small to see down a microscope but large enough to remove several neighbouring genes at once. Think of it as snipping out a short paragraph rather than a whole chapter: a standard karyotype looks normal, yet a handful of genes have quietly gone missing.
Because several adjacent genes are deleted together, these are also called contiguous gene syndromes, and the patient's features reflect the combined loss of all the genes in that interval. The deletions are typically too small for a karyotype, so they are detected by FISH, chromosomal microarray, or sequencing-based methods instead.
Well-known examples include DiGeorge / velocardiofacial syndrome (a deletion at 22q11.2) and Williams syndrome (a deletion at 7q11.23). Many such deletions recur at the same spot because the surrounding DNA contains repeated blocks that misalign during recombination, predisposing that region to loss.
A child with a heart defect and immune problems is tested with FISH for the 22q11.2 region; a missing signal confirms a microdeletion behind DiGeorge syndrome.
Too small for a karyotype, a microdeletion shows up as a missing FISH signal.
A normal karyotype does not rule out a microdeletion; these need FISH or microarray. The clinical picture comes from losing several genes together, not just one.