A new look at XXYY syndrome: medical and psychological features - PubMed (original) (raw)

Multicenter Study

. 2008 Jun 15;146A(12):1509-22.

doi: 10.1002/ajmg.a.32366.

Shanlee Davis, Alison Hench, Sheela Nimishakavi, Renee Beauregard, Ann Reynolds, Laura Fenton, Lindsey Albrecht, Judith Ross, Jeannie Visootsak, Robin Hansen, Randi Hagerman

Affiliations

Multicenter Study

A new look at XXYY syndrome: medical and psychological features

Nicole Tartaglia et al. Am J Med Genet A. 2008.

Abstract

XXYY syndrome occurs in approximately 1:18,000-1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multi-center study of 95 males age 1-55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores <70. Rates of neurodevelopmental disorders, including ADHD (72.2%), autism spectrum disorders (28.3%), mood disorders (46.8%), and tic disorders (18.9%), were elevated with 55.9% on psychopharmacologic medication overall. Recommendations for evaluation and treatment are summarized.

2008 Wiley-Liss, Inc.

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Figures

Fig. 1

Fig. 1

Facial features in XXYY syndrome across different age groups. Note varying degree of dysmorphic features between individuals. Common facial features include mild hypertelorism, narrow and upslanting palpebral fissures, and full lips. In adulthood a long face, prominent brow, and bitemporal narrowing are common.

Fig. 2

Fig. 2

Common physical features in XXYY syndrome including clinodactyly of varying severity, hypotonia with genu valgum and pes planus with pronation at the ankles, and cubitus varus.

Fig. 3

Fig. 3

Brain MRI findings of frontal lobe white matter hyperintensities in XXYY. a: Axial flair MR image shows multiple rounded sub-centimeter foci of increased signal in bifrontal superficial and deep periventricular white matter in a 3-year-old male. b: 12-year-old male. Axial T2 MR image shows multiple foci of increased signal in bifrontal and biparietal superficial and deep periventricular white matter (smaller, but more diffusely distributed compared to image A).

Fig. 4

Fig. 4

Mean verbal IQ, performance IQ, and full-scale IQ in different age groups. Verbal IQ decreases with age. There is no significant change in performance or full-scale IQ. [Color figure can be viewed in the online issue, which is available at

www.interscience.wiley.com

.]

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References

    1. Abramsky L, Chapple J. 47,XXY (Klinefelter syndrome) and 47,XYY: Estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat Diagn. 1997;17:363–368. - PubMed
    1. Aksglaede L, Skakkebaek NE, Juul A. Abnormal sex chromosome constitution and longitudinal growth: Serum levels of IGF-1, IGFBP-3, LH, and testosterone in 109 males with 47,XXY, 47,XYY or SRY-positive 46,XX karyotypes. J Clin Endocrinol Metab. 2008;93:169–176. - PubMed
    1. Alter M, Gorlin R, Yunis J, Peagler F, Bruhl H. Dermatoglyphics in XXYY Klinefelter's syndrome. Am J Hum Genet. 1966;18:507–513. - PMC - PubMed
    1. Barr ML, Carr DH, Soltan HC, Wiens RG, Plunkett ER. The XXYY variant of Klinefelter's syndrome. Can Med Assoc J. 1964;90:575–580. - PMC - PubMed
    1. Baughman F. Klinefelter syndrome and essential tremor. Lancet. 1969;2:545. - PubMed

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