Translocation (Y;22) resulting in the loss of SHOX and isolated short stature

Abstract

Chromosomal rearrangements involving both chromosome Y and chromosome 22 are rare, and may result in a number of different phenotypes. We report on a 4-year-old child with short stature and a dicentric chromosome with a deletion of the distal end of chromosome Yp. The pregnancy was uneventful, until intra-uterine growth retardation was noted. Prenatal karyotyping showed a (Y;22) translocation. No structural fetal abnormality was shown at ultrasound examination, and the pregnancy went to term. A growth-retarded boy with an otherwise normal physical examination was delivered at 39 weeks. At age 4, the child had short stature (-3 SD) without mental retardation. Radiological examination of the wrist was normal. A blood karyotype confirmed the chromosomal rearrangement previously seen on the amniotic fluid cells. C-banding showed a dicentric chromosome, and fluorescence in situ hybridization (FISH) with centromeric probes confirmed the presence of both chromosome Y and 22 centromeres on the derivative chromosome. The karyotype was thus 45,X,der(Y;22)(p11;q11)del(Y)(p11p11). Our patient's phenotype and chromosomal rearrangement prompted us to further investigate the distal Yp region. FISH using a subtelomeric probe showed a deletion of the distal Yp region. This technique also revealed that this chromosomal rearrangement resulted in the deletion of SHOX but not SRY. Although haploinsufficiency of SHOX may result in Léri-Weill Dyschondrosteosis, this diagnosis did not seem obvious in this young patient. This observation confirms the importance of FISH in the investigation of chromosomal abnormalities, and further delineates the phenotype of SHOX deleted patients.