• FISH
• PAX2 gene
• chromosome imbalance
• subtelomeric cryptic rearrangement

• BAC, bacterial artificial chromosome
• FISH, fluorescence in situ hybridisation
• PAC, P1 artificial chromosome
• PCR, polymerase reaction
• VEP, visual evoked potential
• VUR, vesicoureteric reflux

Several papers have recently shown that 6–7% of retarded patients with unclassified malformation syndromes and normal routine cytogenetic analysis have cryptic rearrangements involving subtelomeric regions.¹ About half of these patients have familial unbalanced translocations, the other half have de novo deletions,² and very few cases have duplications.³ The existence of subtelomeric imbalances with only minor or even absent phenotypic effects has been hypothesised and subsequently demonstrated,^3–8 thanks to the increased use of telomeric screening on many groups of patients, tested with different methodologies and selected with different clinical ascertainment criteria.¹ When an unbalanced rearrangement is found both in a proband with an abnormal phenotype and in one of his or her normal parents, the following hypotheses can be made: (1) the rearrangement represents a genomic polymorphism; (2) the imbalance is bigger in the proband than in the phenotypically normal parent; (3) the unbalanced region contains imprinted genes so that the supernumerary/deleted gene is inactive in the normal parent and becomes active in the child; (4) the remaining allele of one of the genes deleted in the submicroscopic rearrangement is mutated in the proband but not in the phenotypically normal parent so that he or she still has a normal copy of that gene. We studied a cryptic rearrangement of chromosome 22q resulting in distal trisomy for both 6p and 20q. The same der(22) was present in the proband, a patient with normal IQ affected by bilateral chorioretinal coloboma and grade IV bilateral vesicoureteric reflux (VUR), and in his clinically normal father. The size of the duplicated 6p and 20q chromosome regions and their gene content were investigated to define the impact of the trisomic segments on the phenotype.