45,X/46,XY mosaicism: a cause of short stature in males

Abstract

45,X/46,XY mosaicism is associated with a broad spectrum of phenotypes ranging from apparently normal male development to individuals with incomplete sexual differentiation and clinical signs of Turner syndrome in both males and females. The most common presentation among individuals with a 45,X/46,XY karyotype is sexual ambiguity, accounting for approximately 60% of cases, while the least common category of 45,X/46,XY patients consists of those with bilaterally descended testes, found in 11-12%. We report on two patients with an apparently normal male phenotype and 45,X/46,XY mosaicism who were diagnosed postnatally because of short stature. Both of these boys presented at the age of 15 years with short stature, minor Turner-like stigmata, normal male external genitalia and spontaneous pubertal development. One of them had coarctaction of the aorta with bicuspid aortic valve, an uncommon clinical feature in boys with mosaicism. The same patient underwent a trial of GH replacement therapy with poor response and his sperm analysis revealed azoospermia. Like our patients, most mosaic 45,X/46,XY children with bilateral scrotal testes go unrecognised at birth and throughout childhood unless they have somatic features of Turner syndrome or significant growth retardation. We recommend that boys with otherwise unexplained short stature, being short for their families, should be karyotyped routinely as is recommended in short-stature girls. In addition, boys with 45,X/46,XY mosaicism require a thorough clinical evaluation similar to that performed in girls with Turner syndrome and must be routinely followed up for their potential to respond favorably to GH treatment and for late onset abnormalities, such as infertility and gonadal tumors.

Growth in Boys with 45,X/46,XY Mosaicism: Effect of Growth Hormone Treatment on Statural Growth

“…GH deficiency has been rarely reported in boys with 45,X/46,XY mosaicism [Efthymiadou et al, 2012]. Thus, classic GH deficiency likely does not occur in this disorder [Richter-Unruh et al, 2004], as confirmed by the normal GH response to provocative stimuli [Bertelloni et al, 2015].…”

“…45,X/46,XY mosaicism is rare (0.23/1.000 amniocenteses or 1.7/10.000 newborns) [Chang et al, 1990;Huang et al, 2002], but likely underestimated; in fact, short stature, a well-known feature of these children [Gantt et al, 1980;Knudtzon and Aarskog, 1987;Telvi et al, 1999;Lindhardt Johansen et al, 2012], may be the only clinical finding, and affected boys may go unrecognized if signs of MGD are not present and/or karyotyping is not performed [Richter-Unruh et al, 2004;Lee et al, 2006;Jacobsen and Cohen, 2008;Lara Orejas et al, 2008;Efthymiadou et al, 2012].…”

Clinical aspects of 49 infertile males with 45,X/46, XY mosaicism karyotype: A case series

“…45,X/46,XY that sometimes referred to as mixed gonadal dysgenesis is a rare mosaicism associated with a wide range of phenotypes in both males and females, from normal cases to individuals with incomplete sexual differentiation and clinical signs of Turner's syndrome. It most probably arises through anaphase lag during mitosis (in the zygote), although Y chromosomal abnormalities and interchromosomal rearrangements with loss of structural abnormal Y material are sometimes seen, and seems to be a common mechanism for the variants (Efthymiadou, Stefanou, & Chrysis, ; Kronenberg & Williams, ). In 45,X/46,XY mosaicism cases, there is the concurrent presence of a X monosomy lineage (45,X) and another with male formation (46,XY).…”

A rare case of male Turner syndrome for penetrating keratoplasty

“…7,8 The most common presentation of 45,X/46,XY karyotype is phenotypically normal male, next being genital ambiguity. 9 The male turner syndrome is one of the rarest presentations and with its complexities calls for a through anaesthetic planning.…”