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Abstract

We report three generation family that includes two patients with severe mental retardation and additional anomalies who have been studied, clinically, cytogenetically, and molecular cytogenetically. A clinical diagnosis could not be made in the propositus, but facial anomalies of Down syndrome (DS) were recognized in the maternal uncle of the propositus. In view of a strong family history of recurrent miscarriage, a familial translocation was highly suggestive. Standard cytogenetic analysis did not reveal any abnormalities. Fluorescence in situ hybridization (FISH) using subtelomeric DNA probes identified a familial cryptic translocation of chromosomes 18 and 21, resulting in partial trisomy 21 and partial monosomy 18q in both patients. FISH analysis of obligate carriers demonstrated a balanced translocation between the terminal parts of 18q and 21q. Including this family, a total of six different familial cases with cryptic or subtle subtelomeric translocations of chromosome 21q has been reported, of which three involved terminal parts of chromosome 18q. The remarkable similarity of the chromosomal breakpoints of our patients and the described families prompted us to refine the breakpoints and to discuss phenotypic differences between these patients. Our results reinforce the role of cryptic subtelomeric rearrangements in patients with mental retardation associated with physical anomalies and stress the importance of FISH technology to supplement routine cytogenetics.