A new look at XXYY syndrome: Medical and psychological features

Nicole Tartaglia, Shanlee Davis, Alison Hench, Sheela Nimishakavi, Renee Beauregard, Ann Reynolds, Laura Fenton, Lindsey A Loomba-Albrecht, Judith Ross, Jeannie Visootsak, Robin L Hansen, Randi J Hagerman

Research output: Contribution to journalArticle

92 Scopus citations

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, multicenter 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.

Original languageEnglish (US)
Pages (from-to)1509-1522
Number of pages14
JournalAmerican Journal of Medical Genetics, Part A
Volume146
Issue number12
DOIs
StatePublished - Jun 15 2008

Keywords

  • ADHD
  • Autism spectrum disorder
  • Klinefelter syndrome
  • Sex chromosome abnormality
  • Tremor
  • XXYY syndrome

ASJC Scopus subject areas

  • Genetics(clinical)

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    Tartaglia, N., Davis, S., Hench, A., Nimishakavi, S., Beauregard, R., Reynolds, A., Fenton, L., Loomba-Albrecht, L. A., Ross, J., Visootsak, J., Hansen, R. L., & Hagerman, R. J. (2008). A new look at XXYY syndrome: Medical and psychological features. American Journal of Medical Genetics, Part A, 146(12), 1509-1522. https://doi.org/10.1002/ajmg.a.32366