48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome

Abstract

Sex chromosome tetrasomy and pentasomy conditions occur in 1:18 000–1:100 000 male births. While often compared with 47,XXY/Klinefelter syndrome because of shared features including tall stature and hypergonadotropic hypogonadism, 48,XXYY, 48,XXXY and 49,XXXXY syndromes are associated with additional physical findings, congenital malformations, medical problems and psychological features. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype–phenotype relationships and the development of evidence-based treatments. Conclusion The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments.

A rare sex chromosome aneuploidy: 48,XXYY syndrome

“…The above-mentioned dysmorphic findings and truncal obesity were present also in our patient. Submucosal or hidden cleft palate have been reported previously, whereas incomplete cleft lip found in our patient has not been identified in previous cases (6). Toe deformities found in our patient are another dysmorphic finding which has not been identified before.…”

“…Tartaglia et al (5) reported that increase in height accelerated especially from the period of puberty. While long height has also been reported in 48,XXXY syndrome, individuals with 48 XXXXY syndrome are mostly short (6). Although our patient was in the prepubertal period, his height was in the 90th percentile.…”

48, XXYY Genotype: Case Report of a Rare Clinical Syndrome

“…48, XXYY syndrome is extremely rare with an incidence of 1:18000 -1: 100,000 males [4,[9][10][11]. 48, XXYY syndrome is usually caused by double non-disjunction occurring at both the first and second meiotic division during spermatogenesis and fusion of the resulting 25, XYY spermatozoon with a 23, X ovum, or nondisjunction at the second meiotic division in both parents resulting in the fusion between a 24, XX ovum and a 24, YY sperm [2].…”

“…With each additional X chromosome there is progressive divergence from the normal with increased frequency of phenotypic, endocrine and structural abnormalities [3]. Poly X-syndrome, often described in literature as a variant of KS, is much rarely reported with a prevalence of 1:18,000-1:100,000 male births and has more pronounced congenital malformations and associated medical comorbidities [4]. We describe a case of a patient who had a formal diagnosis of classic KS from a very young age of 14, presented with not only behavioral and cognitive impairment but also with a wide spectrum of medical complications and further identified on reassessment as XXYY genotype.…”

Problematic Sexual Behavior in a Patient of 48, XXYY Syndrome: A Case Report

“…Physical characteristics include dysmorphic facial features, elbow abnormalities and poor muscle development. Common medical problems are asthma, peripheral vascular disease, diabetes and intention tremors [3]. The presence of an extra Y chromosome affects neurodevelopment, resulting in developmental delays, learning disabilities, intellectual disabilities, and a spectrum of psychological disorders which differentiates it from Klinefelter syndrome (47, XXY), in which the intellect usually falls in the average range (IQ = 80-120) [4,5].…”