XXYY Sibling Project
Brothers and sisters of boys and men with XXYY share what it means to grow up with XXYY.
Early Male Fertility Preservation Program for X and Y Variations
Presentation slides from the 2017 AXYS Family Conference presentation:
Early Male Fertility Preservation Program for X and Y Variations (PDF)
Presented by Hooman Sadri-Ardekani, MD, PhD
Testosterone Therapy for Individuals with Sex Chromosome Aneuploidies
Presentation slides from the 2017 AXYS Family Conference presentation:
Presented by Alan D. Rogol, MD PhD
Thinking About Starting Testosterone for XXY/XXYY/XXXY
Presentation slides from the 2017 AXYS Family Conference presentation:
Thinking About Starting Testosterone for XXY/XXYY/XXXY (PDF)
Presented by Shanlee Davis, MD, MSCS
Klinefelter Syndrome and Other Sex Chromosomal Aneuploidies
Article Title: Klinefelter syndrome and other sex chromosomal aneuploidies
Author: Jeannie Visootsak and John M. Graham Jr.
Date of Publication: October 24, 2006
The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY) to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH). The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15–16 points, with language most affected, particularly expressive language skills.
ADHD Symptoms in Children and Adolescents with Sex Chromosome Aneuploidy: XXY, XXX, XYY, and XXYY
Article title: Attention-Deficit Hyperactivity Disorder Symptoms in Children and Adolescents with Sex Chromosome Aneuploidy: XXY, XXX, XYY, and XXYY
Authors: Nicole R. Tartaglia, MD, Natalie Ayari, BA, Christa Hutaff-Lee, PhD, Richard Boada, PhD
Date of Publication: May 2012
Please share this article with your healthcare providers and with other professionals (therapists, school support staff and administrators, etc.).
Timing of Diagnosis of 47,XXY and 48,XXYY: A Survey of Parent Experiences
Article Title: Timing of Diagnosis of 47,XXY and 48,XXYY: A Survey of Parent Experiences
Authors: Jeannie Visootsak, Natalie Ayari, Susan Howell, Joash Lazarus, and Nicole Tartaglia
Date of Publication: January 15, 2013
Clinical research: Extra X impairs awareness of others’ minds
Article Title: Clinical research: Extra X impairs awareness of others’ minds
Author: Kate Yandell
Date of Publication: June 13, 2014
“Girls and boys born with an extra X chromosome both tend to have difficulties understanding the minds of others, but for different reasons than children with autism do, according to a study published 22 March in Genes, Brain and Behavior” (Sophie van Rijn et al).
48,XXYY, 48,XXXY and 49,XXXXY Syndromes: Not Just Variants of Klinefelter Syndrome
Article Title: 48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome
Authors: Tartaglia, Ayari, Howell, D’Epagnier, Zeitler
Date of Publication: April 9, 2011
“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.”
Brain and behavior in 48,XXYY syndrome
Article Title: Brain and behavior in 48, XXYY syndrome
Authors: Alli P. Hanley, Jonathan D. Blumenthal, Nancy Raitano Lee, Eva H. Baker, Liv S. Clasen, Jay N. Giedd
Date of Publication: April 15, 2015
“The phenotype of 48, XXYY syndrome (referred to as XXYY) is associated with characteristic but variable developmental, cognitive, behavioral and physical abnormalities. To discern the neuroanatomical phenotype of the syndrome, we conducted quantitative and qualitative analyses on MRI brain scans from 25 males with XXYY and 92 age and SES matched typically developing XY males. Quantitatively, males in the XXYY group had smaller gray and white matter volumes of the frontal and temporal lobes. Conversely, both gray and white matter volumes of the parietal lobe as well as lateral ventricular volume were larger in the XXYY group. Qualitatively, males in the XXYY group had a higher incidence of colpocephaly (84% vs. 34%, p ≤ 0.001), white matter lesions (25% vs. 5%, p = 0.007), and thin posterior body of the corpus callosum (28% vs. 3%, p = 0.001). The specificity of these findings may shed light on the role of the X and Y chromosomes in typical and atypical brain development and help provide direction for future studies of brain–behavior relationships in males with XXYY syndrome.”