Other Variations

/Other Variations

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.

Read more

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

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|

Effects of short-course androgen therapy on the neurodevelopmental profile of infants and children with 49,XXXXY syndrome


Aim: The aim of this investigation was to ascertain whether an early course of androgen treatment (three injections testosterone enanthate, 25 mg) could have a positive impact on any domains of neurodevelopmental function in boys with 49,XXXXY.

Methods: A total of 22 boys with a karyotype of 49,XXXXY participated in a multidisciplinary assessment of neurocognition, speech and language, paediatric neurology and endocrinology evaluations. One group had received early androgen and another group did not receive any hormonal treatment prior to the evaluation. The mean age of treatment for Group 1 was 12 months with the mean age of first evaluation 74 months. The mean age of first evaluation for Group 2 was 87 months. Statistical analysis was completed to determine whether there was a positive treatment effect from androgen therapy.

Results: There was a significant positive treatment effect in speech and language domain, gestural communication and vocabulary development. No treatment effect was seen on nonverbal capacities.

Conclusion: Our findings revealed improved function in several areas of development which had been severely delayed in boys with 49,XXXXY. Continued research is underway to expand our understanding of the relationship of androgen, brain function and behavioural outcome in boys with 49,XXXXY.

Link to Article

Categories: Other Variations|Tags: |

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

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. 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 more

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

What is Intersex?

Organisation Intersex International
Published: 2010

INTERSEX is congenital difference in anatomical sex. That is, physical differences in reproductive parts like the testicles, penis, vulva, clitoris, ovaries and so on.  Intersex is also physical differences in secondary sexual characteristics such as muscle mass, hair distribution, breast development and stature.  Intersex can include things that are invisible to the eye such as chromosomal and hormonal differences. Those kinds of
differences usually have a manifestation in primary or secondary sexual anatomy that is visible either externally or internally.  Brain differences may account for both homosexuality and transsexualism, but intersex isn’t brain sex alone.  We are intersex because it is thought the kinds of differences in our anatomy seem to be either male and female at the same time or not quite male or female or neither male or female.  So we have physical differences that confuse medicine’s anatomical ideal of male and female. Intersex is not always immediately apparent because in our society we do not commonly look at each other’s genitals or internal organs.

Click to read the entire article.

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