Short Stature on a Boy: Mosaicism with an Isodicentric Y Chromosome

Abstract

Mosaicism brings great variability into the clinical expression of numerical and structural chromosomal abnormalities. The phenotypic variability of 45,X/46,XY mosaicism extends from Turner syndrome to apparently physically normal males. We present a case of a 14-year-old adolescent with short stature and delayed puberty, who was admitted in a Paediatric Endocrinology outpatient clinic. After a careful investigation, he was found to have a 45,X/46,X,idic(Y)(p11.32) mosaicism. This case report emphasizes the wide range of etiologies that can be involved in short stature and that chromosomal study is an important tool when firstly approaching males with short stature, avoiding unnecessary tests. There is an important clinical need for gonadal follow-up in this situation and for support in the decision about sex of rearing and sex orientation, when justifiable.

Gender-Discordant Monochorionic-Diamniotic Twins Both With 45,X/46,X, Idic(Y) Mosaicism and a Novel Deletion Within the TBC1D5 Gene

“…11 In 45,X/46,XY males, gonadectomy is reserved for patients with sexual ambiguity including cryptorchidism or hypospadias since SRY appears protective against malignancy. 12 Silvestre et al suggested the use of an external masculinization score (EMS) to assess risk of malignancy in 45,X/46,XY patients due to an inverse correlation between higher EMS scores and risk of gonadal malignancy. 12 In males, germ cell tumors are more often associated with intra-abdominal gonads.…”

“…12 Silvestre et al suggested the use of an external masculinization score (EMS) to assess risk of malignancy in 45,X/46,XY patients due to an inverse correlation between higher EMS scores and risk of gonadal malignancy. 12 In males, germ cell tumors are more often associated with intra-abdominal gonads. 7 It has been suggested that 45, X/46,XY males with nearly normal external genitalia may be assessed periodically by ultrasound or physical palpation of the gonads.…”

“…Isodicentric Y chromosomes are considered relatively unstable structurally. 12 Due to this instability, it is believed that cell lines may lose the unstable Y chromosome and thus only contain a single X chromosome. 12 Thus, in our case, perhaps the mosaicism observed may be due in part to an unstable isodicentric Y chromosome.…”

“…12 Due to this instability, it is believed that cell lines may lose the unstable Y chromosome and thus only contain a single X chromosome. 12 Thus, in our case, perhaps the mosaicism observed may be due in part to an unstable isodicentric Y chromosome. Generation of an isodicentric Y chromosome, as observed in our case, is usually de novo from paternal gametogenesis but rarely due to a postzygotic event.…”

Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing

“…Isochromosomes have been reported in prenatal testing and are predominantly observed in advanced maternal age pregnancies [24]. The isodicentric Y chromosome has been associated with variable outcomes for which few reports have found it compatible with a normal male phenotype in absence of other abnormalities [24,25], while other have reported cases with short stature [26] and mixed gonadal dysgenesis [27]. Similarly, isodicentric X chromosome has been reported with a normal female phenotype [28] and refractory anemia in a case of active isodicentric X [29].…”