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Review
. 2011 Jun;100(6):851-60.
doi: 10.1111/j.1651-2227.2011.02235.x. Epub 2011 Apr 8.

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

Nicole Tartaglia  1 , Natalie Ayari, Susan Howell, Cheryl D'Epagnier, Philip Zeitler
Affiliations
Review

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

Nicole Tartaglia et al. Acta Paediatr. 2011 Jun.

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.

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Figures

Figure 1
Figure 1
Facial features in 48,XXYY, 48,XXXY and 49,XXXXY syndromes. Photograph of facial features in children and adults with XXYY (A, B, D, G, H), XXXY (D, F) and XXXXY (E) syndromes. Note features of hypertelorism (A, D, E), epicanthal folds (A, E, G), narrow palpebral fissures (A, C, E, F), strabismus (C, E), flattened occiput (A, C, D) and low frontal hairline (A, B, E, F). Note the sparse facial hair (C, F, G), prominent brow (C, F, G) and narrow shoulders (H) in the adults.
Figure 2
Figure 2
Photograph of Physical features in XXYY, XXXY and XXXXY including: (A) Fifth-digit clinodactyly (and nail biting), (B) prominent elbows with hyperextensibility and (C) lower extremities with low muscle bulk in the calves, flat feet and mild pronation at the ankles.
See this image and copyright information in PMC

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