49,XXXXY Syndrome with Diabetes Mellitus

Abstract

49,XXXXY syndrome is a rare sex chromosome aneuploidy and characterized by mental retardation, skeletal defects, craniofacial anomalies and hypogonadism. The increased frequency of diabetes mellitus in patients with Klinefelter syndrome and other types of X-chromosome polysomy has been reported, but no cases of diabetes mellitus in adult with 49,XXXXY syndrome have been reported so far. We report an 18-year-old patient with 49,XXXXY syndrome accompanying diabetes mellitus.

49,XXXXY Syndrome with Autoimmune Diabetes and Ocular Manifestations

“…The case reported by Christensen and Therkelsen [6] was glucose intolerant after an oral glucose tolerance test, but not a true diabetic. Kim et al [7] reported a diabetic 49,XXXXY case, in which insulin treatment was shifted to oral anti-diabetics and there was a positive family history for type 2 diabetes. The incidence of type 2 diabetes is reported to be high in syndromes with Xpolysomy, but a definite mechanism other than hypogonadism is unknown [8] .…”

Changes in chromosome positioning may contribute to the development of diseases related to X‐chromosome aneuploidy

“…There are many diseases associated with polysomy of one or another chromosome (Fryns et al, 1995;Samango-Sprouse, 2001;Swerdlow et al, 2001;Beyer et al, 2005;Kim et al, 2006). An imbalance of gene expression is usually considered to be the cause of the above diseases.…”

“…Indeed, it is known that extra copies of X chromosome are inactivated in the same fashion as one of two copies of X chromosome in normal female cells. Nevertheless X chromosome polysomies cause diabetes and numerous other diseases (Swerdlow et al, 2001;Kim et al, 2006). One may consider a possibility that in cells with three extra copies of X chromosome there is a shortage of components necessary for X chromosome inactivation.…”

“…Edwards syndrome (trisomy 18) is characterized by disturbances in the functions of vital organs (in most cases of brain, heart, kidney, and gut) which cause the death of 90% of patients within the first year (Hassold and Jacobs, 1984). A rare sex syndrome (49, XXXXY) is characterized by mental retardation and skeletal defects (Kim et al, 2006). Klinefelter syndrome (47,XXY; 48,XXXY) is characterized by infertility (azoospermia or oligospermia), osteoporosis (in young or middle-aged men), motor delay or dysfunction, etc (Wattendorf and Muenke, 2005).…”

Testosterone replacement in 49,XXXXY syndrome: andrological, metabolic and neurological aspects

“…This aneuploidy probably originates from non-disjunction of the X chromosome during both meiosis I and II. To date, few cases have been described (1) (2) (3) (4) (5) (6) (7) (8) (9); in such cases, the median age at the time of diagnosis was 4 months (2) (3). Some particular ultrasound findings (polyhydramnios or cystic hygroma) could be suggestive of this syndrome during pregnancy (4).…”