XXYY Sibling Project

Brothers and sisters of boys and men with XXYY share what it means to grow up with XXYY.

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Categories: 48,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

Categories: 47,XXY (Klinefelter), 48,XXYY, Other Variations|Tags: |

Testosterone Therapy for Individuals with Sex Chromosome Aneuploidies

Presentation slides from the 2017 AXYS Family Conference presentation:

Testosterone Therapy for Adolescents/Adults with Sex Chromosome Aneuploidies: What’s Available and What’s New? (PDF)

Presented by Alan D. Rogol, MD PhD


Categories: 47,XXY (Klinefelter), 48,XXYY, Other Variations|Tags: |

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

Categories: 47,XXY (Klinefelter), 48,XXYY, Other Variations|Tags: |

Klinefelter Syndrome and Other Sex Chromosomal Aneuploidies

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.

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Categories: 47,XXY (Klinefelter), 48,XXYY, Other Variations|

ADHD – More research from the team at the eXtraordinarY Kids Clinic in Denver

Attention-Deficit Hyperactivity Disorder Symptoms in Children and Adolescents with Sex Chromosome Aneuploidy: XXY, XXX, XYY, and XXYY

Tartaglia, Nicole R. MD; Ayari, Natalie BA; Hutaff-Lee, Christa PhD; Boada, Richard PhD

Link to article:

Please share this article with your healthcare providers and with other professionals (therapists, school support staff and administrators, etc.).

Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXYY|

Timing of Diagnosis of 47,XXY and 48,XXYY: A Survey of Parent Experiences

47,XXY/Klinefelter syndrome is the most common sex chromosomal aneuploidy, yet 64% of males with this condition go undiagnosed. 48,XXYY is less common and there is less known about the diagnosis. The objective of this study is to describe the diagnosis experiences of parents of males with 47,XXY and 48,XXYY. Parents of 89 males with 47,XXY and 76 males with 48,XXYY completed a survey that gathered data about their experiences leading to a diagnosis, including the current age of the child, age at diagnosis, reasons for initial concern, and the specialists providing the diagnosis. In the 47,XXY cohort diagnosed
postnatally, 59% presented with developmental delay, with a mean age at first parental concern of 5.2 years and mean age of diagnosis at 10.0 years. The remaining 41% presented with endocrinologic issues with a mean age at first concern of 19.1 years and mean age of diagnosis at 21.1 years. In the 48,XXYYgroup, 93% presented with developmental delay, with mean age at first parental concern of 2.4 years and mean age of diagnosis at 7.6 years. Hence, the average time from initial parental concernto diagnosis of 47,XXY or 48,XXYYranges from 2 to 5 years, with those presenting with developmental issues having a longer lag to diagnosis compared to those presenting with endocrinologic issues. Increased awareness of the developmental, psychological, and medical features of 47,XXY and 48,XXYY is important to facilitate timely diagnosis and initiation of appropriate screenings and treatments that are important for optimal outcomes.

Click here for article.

Categories: 47,XXY (Klinefelter), 48,XXYY|

Clinical research: Extra X impairs awareness of others’ minds

Kate Yandell
Published: June 13, 2014

1.) van Rijn S. et al. Genes Brain Behav. Epub ahead of print (2014)
2.) Bishop D.V. et al. Arch. Dis. Child 96, 954-959 (2011)

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 Behavior1.

In people with autism, deficits in theory of mind — the ability to understand the emotions, intentions and desires of others — often accompany problems with language and facial recognition. By contrast, theory of mind deficits in people with an extra X chromosome are more likely to stem from an inability to pay attention, the study suggests.

Researchers have previously noticed parallels between autism and extra-X disorders. Men with two X chromosomes and a Y chromosome have Klinefelter syndrome and are six times more likely than controls to be diagnosed with autism. There is less information on autism rates in trisomy X, the condition in which girls have three X chromosomes rather than two. One study of 58 women with trisomy X found no autism cases, in keeping with the relative rarity of autism in women2.

The researchers recruited 29 children with Klinefelter syndrome, 17 with trisomy X, 56 with autism and 88 controls, all between the ages of 9 and 18 years. They excluded children with intellectual disability. They tested theory of mind in the children by asking them to identify the perspectives of characters in cartoon images with accompanying text. The children with extra-X disorders or autism all had a relatively difficult time doing so.

Multiple cognitive skills are necessary to conceive of others’ minds, so the researchers wondered whether the children were all having difficulties for the same underlying reasons. They found that in children with an extra X chromosome, performance on the theory of mind tasks tracks with their ability to sustain attention, indicating that their lack of focus sabotages their ability to understand others’ thoughts. Children with autism who struggle with theory of mind tend to have trouble comprehending and using language and recognizing faces.

Finally, the researchers assessed whether difficulties with theory of mind are more common in people with extra X disorders if they show strong signs of autism at an early age. They found that this is not the case. People with the extra-X disorders often show social difficulties, but they may not always meet the full criteria for autism.

Read the original article here.

Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 48,XXYY, Other Variations|

48,XXYY, 48,XXXY and 49,XXXXY Syndromes: Not Just Variants of Klinefelter Syndrome

Tartaglia, Ayari, Howell, D’Epagnier, Zeitler
ePublished: 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. While the spectrum of cognitive abilities extends much higher than originally described, developmental delays, cognitive impairments and behavioural disorders are common and require strong treatment plans. Future research should focus on genotype-phenotype relationships and the development of evidence-based treatments.

The more complex physical, medical and psychological phenotypes of 48,XXYY, 48,XXXY and 49,XXXXY syndromes make distinction from 47,XXY important; however, all of these conditions share features of hypergonadotropic hypogonadism and the need for increased awareness, biomedical research and the development of evidence-based treatments.

Read the entire original article here.

Categories: 48,XXYY, Other Variations|Tags: |

Brain and behavior in 48, XXYY syndrome

ePublished: April 15, 2015

Alli P. Hanley, Jonathan D. Blumenthal, Nancy Raitano Lee, Eva H. Baker, Liv S. Clasen, Jay N. Gied


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.

To read the entire article click here.

Categories: 48,XXYY|


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