Cytogenetic diagnosis of the fragile X syndrome: efficiency, utilization, and trends.

In order to assess the impact of the increasing awareness of the fra(X) syndrome and a broader approach to fra(X) testing, we analyzed our laboratory experience for 1980-1988. In 1981-1986, there was an average of 80 cases/year (62 male; 18 female). The 103 (74 male; 29 female) cases in 1987 represent a 45% increase over the prior 3 years; this sustained in 1988 with 106 cases. The fra(X) positive yield decreased from a high of 49% in 1980 to an average of 20% (range 15-24%) in 1981-1984, 10% (range 9-11%), in 1985-1987 and 7% in 1988. The positive rate for males and females was nearly identical in both time periods. The positive yield for mentally retarded individuals with a family history of mental retardation dropped from an average of 20% for 1981-1984 and 33% for 1985-87 to 13% for 1988; however, the positive fra(X) rate for mentally retarded individuals decreased from an average of 23% in 1981-1984 to 9% in 1985-1987 and 7% in 1988. The decreasing fra(X) yield and increasing case load are directly attributable to the relaxation of criteria for referral and testing related to the referral of all mentally retarded patients, and to the perceived malpractice liability for not doing a "complete" evaluation. Although the burden for cytogenetic laboratories is considerable, the yield of positive fra(X) cases is still worthwhile, and may be maximized by the use of improved screening criteria.