A five-year experience with fragile X testing. Setting laboratory standards of practice and a cost-effective protocol.

During the years 1990-1994, our center tested 652 patients, with a broad range of referral indications, for fragile X syndrome using either cytogenetic analysis alone (Protocol 1) or more recently, a combination of DNA analysis and routine karyotyping (protocol 2). The overall positive rate for fragile X was 3.1% with an incidence of other chromosomal abnormalities (OCAs) of 3.2%. Breakdown of cases using each testing protocol along with percent positives is: [table: see text] Use of Protocol 2 yielded only definitive fragile X results, while more than half of the "positives" using Protocol 1 were equivocal. Historically this has been problematic for both the laboratory and physician since interpretation is often dependent on an equally equivocal clinical picture. Protocol 2 eliminates these diagnostic dilemmas without compromising detection of other chromosomal abnormalities, the incidence of which appears to be unaffected by testing method used. The overall incidence of OCA of 3.2% underscores the value of routine karyotyping in this referral group and likely reflects the phenotypic variability of fragile X and its clinical overlap with other chromosomal abnormalities. We believe that a fragile X testing protocol combining routine karyotyping with definitive molecular technology represents the most cost-effective diagnostic approach to this clinically challenging patient population.