Turner syndrome female with a small ring X chromosome lacking the XIST, an unexpectedly mild phenotype and an atypical association with alopecia universalis

Abstract

Rearranged X chromosome in Turner syndrome (TS) are generally well tolerated but in cases of ring X chromosomes and of X/autosome translocations the incidence of mental retardation and other congenital abnormalities can be significantly higher. These abnormal phenotypes can be ascribed to failed or partial X inactivation. Here, we report a 10-year-old female who was referred for a cytogenetic analysis because she developed an alopecia universalis. The patient, of normal intelligence, had been found to have traits of TS, especially short stature. A first cytogenetic analysis showed a no mosaic 45,X karyotype. Since, the risk of developing gonadoblastoma in TS patients with mosaicism for a Y derivative chromosome and because association of alopecia universalis and TS is uncommon, fluorescence in situ hybridization (FISH) was performed to search for a second cell population. Our patient was found to have a mosaic 45,X/46,X,+r. FISH analysis using sex chromosome probes permitted us to identify the very small marker as a ring X chromosome, detected in 90% of cells. The ring appeared to be formed almost totally of alphoid sequences with breakpoints in the juxtacentromeric region. The r(X) does not include the XIST locus and may, therefore, not be subject to X-inactivation. Unexpectedly mild phenotype in our patient and its association with alopecia universalis will be discussed.