IMPE Abstracts

Background: Translocations involving the X and Y chromosome are rare in humans. Here we describe two cases diagnosed during the investigation of short stature. Case 1: She was born at 38 gestational weeks (GW), with birth weight (BW) SDS -1.5 and birth length (BL) SDS -2.7. At the first assessment, she had a chronological age (CA) of 11.3ys, a height SDS of -2.2, a sitting height-to-height SDS of 4.6, and Madelung´s deformity. The height SDS of her mother and maternal grandmother was -3.5 and -2.0, respectively. A karyotype revealed a 46X t(X;Y) (p22.3; q11.2). Her mother and maternal grandmother have the same alteration. She had normal pelvic ultrasound, echocardiogram, and audiometry. A microarray showed an Xp deletion encompassing 64 genes, including SHOX gene (arr[GRCh38] Xp22.33p22.31(302942-8480277)x1) and Yq gain (arr[GRCh38] Yq11.221q12(13948013-26673214)x1). Case 2: She was born at term with BW SDS -0.9 and BL SDS -1.6. At the first evaluation (CA 10y), she had a height SDS of -2.2 and no Madelung´s deformity. Parents had height above the mean. On initial investigation, she had a karyotype that shows 46,X, add(X)(p22.3). The microarray reveled Xp deletion encompassing 59 genes included SHOX gene (arr[GRCh38] Xp22.33p22.31(624383-8530103)x1) and arr[GRCh38] and Yq gain (Yq11.221q12(14076802-22375261)x1). Parents have normal karyotype. Discussion: The short stature observed in both patients is because SHOX haploinsufficiency. The concern when identifying the Y fragment in the karyotype is that female individual with digenetic gonad and Y-derived seem to have a high risk of developing gonadoblastoma (10–30%). For this reason, gonadectomy is recommended in all females with Turner syndrome and Y-chromosome material. The presence of a predisposing gene mapped in the pericentromeric region of Yp (GBY, gonadoblastoma locus on the Y-chromosome) is associated with this risk. In contrast, in Xp22;Yq11 translocation female, no gonadoblastoma has been described, probably do to the absence of a Y-centromere fragment. The description of a family with three generations of women with 46X t(X;Y) reinforces the orientation of not indicating prophylactic gonadectomy in this cases. Beside the short stature, females may have mild intellectual disability (10%), facial dysmorphism (28%), and cardiac defects (3.4%). Conclusion: As there was not enough lifelong follow-up in this female with 46X t(X;Y) to rule out any risk of development of gonadoblastoma, screening with periodic pelvic ultrasound and tumor markers should be considered.