{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T18:22:32Z","timestamp":1785781352578,"version":"3.56.0"},"reference-count":73,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2008,5,14]],"date-time":"2008-05-14T00:00:00Z","timestamp":1210723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2008,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>XXYY syndrome occurs in approximately 1:18,000\u20131:40,000 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\u2010sectional, multi\u2010center study of 95 males age 1\u201355 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\u2009=\u200922). Common medical problems included allergies and asthma (&gt;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\u2009=\u200935) 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\u2010six percent had full\u2010scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores &lt;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. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32366","type":"journal-article","created":{"date-parts":[[2008,5,14]],"date-time":"2008-05-14T17:16:41Z","timestamp":1210785401000},"page":"1509-1522","source":"Crossref","is-referenced-by-count":129,"title":["A new look at XXYY syndrome: Medical and psychological features"],"prefix":"10.1002","volume":"146A","author":[{"given":"Nicole","family":"Tartaglia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanlee","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Hench","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Nimishakavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Beauregard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fenton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannie","family":"Visootsak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199704)17:4<363::AID-PD79>3.0.CO;2-O"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1426"},{"key":"e_1_2_7_4_1","first-page":"507","article-title":"Dermatoglyphics in XXYY Klinefelter's syndrome","volume":"18","author":"Alter M","year":"1966","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_5_1","first-page":"575","article-title":"The XXYY variant of Klinefelter's syndrome","volume":"90","author":"Barr ML","year":"1964","journal-title":"Can Med Assoc J"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(69)90244-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0347"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3928\/0191-3913-20040701-17","article-title":"Colobomas of the iris and choroid and high signal intensity cerebral foci on T2\u2010weighted magnetic resonance images in Klinefelter's syndrome","volume":"41","author":"Boettger M","year":"2004","journal-title":"J Pediatric Ophthalmol Strabismus"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00312978"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1970.tb02248.x"},{"key":"e_1_2_7_11_1","first-page":"873","article-title":"A probable XXYY sex determining mechanism in a mentally defective male with Klinefelter's syndrome","volume":"84","author":"Carr DH","year":"1961","journal-title":"Can Med Assoc J"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.5.695"},{"key":"e_1_2_7_13_1","unstructured":"CoffeeB AlbizuaI WarrenS.2007.DNA methylation alterations in males with Klinefelter syndrome[Abstract 715]. 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