title: A new look at XXYY syndrome: medical and psychological features.
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.
authors.affiliation: Department of Pediatrics, University of Colorado Denver, School of Medicine, Aurora, Colorado, USA. tartaglia.nicole@tchden.org
authors.forename: Nicole
authors.initials: N
authors.lastname: Tartaglia
authors.forename: Shanlee
authors.initials: S
authors.lastname: Davis
authors.forename: Alison
authors.initials: A
authors.lastname: Hench
authors.forename: Sheela
authors.initials: S
authors.lastname: Nimishakavi
authors.forename: Renee
authors.initials: R
authors.lastname: Beauregard
authors.forename: Ann
authors.initials: A
authors.lastname: Reynolds
authors.forename: Laura
authors.initials: L
authors.lastname: Fenton
authors.forename: Lindsey
authors.initials: L
authors.lastname: Albrecht
authors.forename: Judith
authors.initials: J
authors.lastname: Ross
authors.forename: Jeannie
authors.initials: J
authors.lastname: Visootsak
authors.forename: Robin
authors.initials: R
authors.lastname: Hansen
authors.forename: Randi
authors.initials: R
authors.lastname: Hagerman
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000523:psychology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000523:psychology / Q000628:therapy; D006801:Humans; D007223:Infant; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis* / Q000523:psychology / Q000628:therapy; D008875:Middle Aged; D012729:Sex Chromosome Aberrations; D013577:Syndrome