November 2020 - The Association for X and Y Chromosome Variations

AXYS Klinefelter Syndrome CME Course

CME Course Title: Klinefelter Syndrome: Identifying, characterizing and managing an underdiagnosed condition with serious consequences

Course Directors: Hooman Sadri, MD, PhD and Stuart Howards, MD

Reviewed by the AXYS Clinic & Research Consortium (ACRC)

Date: October 2020

“Introduction:

Have you unknowingly seen someone with Klinefelter Syndrome in your practice?

Chances are, you have. Klinefelter Syndrome (KS) is the most common sex chromosome disorder, occurring in approximately 1 out of every 600 male births. Yet an estimated 60 to 75% of those with KS will remain undiagnosed throughout their lifetimes.

Why does this matter?

It matters because KS is linked to significantly higher mortality rates and a range of physical, neurocognitive, and social/behavioral comorbidities as well as a lower quality of life and socioeconomic status. Some healthcare providers believe that delayed diagnosis can increase patient morbidity. And it matters because those with KS are getting lost in our healthcare system. Studies show that the majority of individuals with KS report being dissatisfied with their care. In addition, many with KS and their families find that their providers have outdated information about the condition, or little information at all. By learning more about the many facets of KS, providers across the healthcare system can work together to better treat and support those with this condition and their families.”

Rick Frith2020-11-28T15:55:52-05:00Categories: 47,XXY (Klinefelter), Resources|Tags: CME|

The Expert in the Room

Article Title: The Expert in the Room: Parental Advocacy for Children with Sex Chromosome Aneuploidies

Authors: Richardson, Riggan, and Allyse

Date of Publication: November 2, 2020

“Owing to fragmentation in the medical system, many parents of children with disabilities report taking on a care coordinator and advocate role. The parental advocacy and care coordination requirements are further amplified in this population because of a lack of awareness about sex chromosome aneuploidies (SCAs) in medical and social services settings, as well as the complex needs of affected children. This burden disproportionately affects mothers and low-resource families as a result of gendered ideas of parenthood and social stratification in resource access. The aim of this study is to understand the unique parental burdens of SCAs and family support needs.”

Rick Frith2020-11-13T15:01:37-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXXY, 48,XXYY, All Variations, Other Variations|Tags: Advocacy|

Metabolic and cardiovascular risk factors in Klinefelter syndrome

Article Title: Metabolic and cardiovascular risk factors in Klinefelter syndrome

Authors: Spaziani and Radicioni

Date of Publication: June 2020

“Klinefelter syndrome (KS), which normally presents with a 47,XXY karyotype, is the most common sex chromosome disorder in males. It is also the most common genetic cause of male infertility. KS subjects are typically tall, with small and firm testes, gynecomastia, broad hips, and sparse body hair, although a less evident presentation is also possible. KS is also characterized by a high prevalence of hypogonadism, metabolic syndrome (MetS) and cardiovascular disease. The aim of this article is to systematically review metabolic and the cardiovascular risk factors in KS patients. Hypogonadism has an important role in the pathogenesis of the changes in body composition (particularly visceral obesity) and hence of insulin resistance and MetS, but the association between KS and MetS may go beyond hypogonadism alone. From childhood, KS patients may show an increase in visceral fat with a reduction in lean body mass and an increase in glucose and impaired fat metabolism. Their increased incidence of congenital anomalies, epicardial adipose tissue, and thromboembolic disease suggests they have a higher risk of cardiovascular disease. There is conflicting evidence on the effects of testosterone therapy on body composition and metabolism.”

Rick Frith2020-11-05T15:04:15-05:00Categories: 47,XXY (Klinefelter)|

Minipuberty in Klinefelter syndrome: Current status and future directions

Article Title: Minipuberty in Klinefelter syndrome: Current status and future directions

Authors: Aksglaede, Davis, Ross, and Juul

Date of Publication: June 2020

“Klinefelter syndrome is highly underdiagnosed and diagnosis is often delayed. With the introduction of non-invasive prenatal screening, the diagnostic pattern will require an updated description of the clinical and biochemical presentation of infants with Klinefelter syndrome. In the first months of life, the hypothalamic–pituitary–gonadal (HPG)-axis is transiently activated in healthy males during the so-called minipuberty. This period represents a “window of opportunity” for evaluation of the HPG-axis before puberty and without stimulation tests. Infants with Klinefelter syndrome present with a hormonal surge during the minipuberty. However, only a limited number of studies exist, and the results are contradictory. Further studies are needed to clarify whether infants with Klinefelter syndrome present with impaired testosterone production during the minipuberty. The aim of this review is to describe the clinical and biochemical characteristics of the neonate and infant with Klinefelter syndrome with special focus on the minipuberty and to update the clinical recommendations for Klinefelter syndrome during infancy.”

Rick Frith2020-11-05T14:58:50-05:00Categories: 47,XXY (Klinefelter)|

Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome

Article Title: Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome

Authors: Skakkebæk, Gravholt, Chang, Moore, and Wallentin

Date of Publication: June 2020

“Klinefelter syndrome (KS; 47,XXY) impacts neurodevelopment and is associated with an increased risk of cognitive, psychological and social impairments, although significant heterogeneity in the neurodevelopmental profile is seen. KS is characterized by a specific cognitive profile with predominantly verbal deficits, preserved function in non-verbal and visuo-spatial domains, executive dysfunction and social impairments, and by an increased vulnerability toward psychiatric disorders. The neurobiological underpinnings of the observed neuropsychological profile have not been established. A distinct pattern of both global and regional brain volumetric differences has been demonstrated in addition to preliminary findings of functional brain alterations related to auditory, motor, language and social processing. When present, the combination of cognitive, psychological and social challenges has the potential to negatively affect quality of life. This review intends to provide information and insight to the neuropsychological outcome and brain correlates of KS. Possible clinical intervention and future directions of research will be discussed.”

Rick Frith2020-11-05T14:39:25-05:00Categories: 47,XXY (Klinefelter)|

Executive function in XXY: Comparison of performance-based measures and rating scales

Article Title: Executive function in XXY: Comparison of performance-based measures and rating scales

Authors: Janusz, Harrison, C. Boada, Cordeiro, Howell, Tartaglia, and R. Boada

Date of Publication: June 2020

“Few studies have systematically assessed executive functioning (EF) skills in boys with XXY, and these are limited by small samples and restricted EF assessment. This study used a broader battery of performance-based measures as well as parent-rating scales of EF in 77 boys and adolescents with XXY (mean age = 12.5 years), recruited from a clinical trial and an outpatient clinic. Exploratory factor analyses were used to create EF domains from performance-based measures, and similar domains were measured using the Behavior Rating Inventory of Executive Function and Conners Parent-Rating Scales. The boys with XXY showed a distinct EF profile, with the greatest deficit in attention and more moderate deficits in working memory, switching, and planning/ problem solving. Parent ratings showed similar challenges, as well as impaired inhibition. Independent sample t-tests showed no difference on performance measures between boys diagnosed or not diagnosed with attention-deficit/hyperactivity disorder (ADHD), although parents of boys diagnosed with ADHD reported more difficulties. There were no differences on performance-based tests between those diagnosed pre- and postnatally, although parents of postnatally diagnosed boys reported more metacognitive problems. Language deficits, cognition, and socio-economic status did not account for EF deficits.”

Rick Frith2022-02-25T17:07:32-05:00Categories: 47,XXY (Klinefelter)|Tags: ADHD, Executive Function|

High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome

Article Title: High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome

Authors: Davis, DeKlotz, Nadeau, Kelsey, Zeitler, and Tartaglia

Date of Publication: June 2020

“Klinefelter syndrome (KS) occurs in 1:600 males and is associated with high morbidity and mortality due to diabetes and cardiovascular disease. Up to 50% of men with KS have metabolic syndrome, a cluster of features conferring increased risk for diabetes and cardiovascular disease. These cardiometabolic (CM) risk features have not been studied in adolescents with KS. The objective of this cohort study was to compare CM risk features in adolescents with KS to controls matched for sex, age, and BMI z score.”

Rick Frith2020-11-05T12:49:50-05:00Categories: 47,XXY (Klinefelter)|

Diminished Ovarian Reserve in Girls and Adolescents with Trisomy X Syndrome

Article Title: Diminished Ovarian Reserve in Girls and Adolescents with Trisomy X Syndrome

Authors: Davis, Soares, Howell, Cree-Green, Buyers, Johnson, and Tartaglia

Date of Publication: June 2020

“An extra X chromosome occurs in ~ 1 in 1000 females, resulting in a karyotype 47,XXX also known as trisomy X syndrome (TXS). Women with TXS appear to be at increased risk for premature ovarian insufficiency; however, very little research on this relationship has been conducted. The objective of this case-control study is to compare ovarian function, as measured by anti-mullerian hormone (AMH) levels, between girls with TXS and controls. Serum AMH concentrations were compared between 15 females with TXS (median age 13.4 years) and 26 controls (median age 15.1 years). Females with TXS had significantly lower serum AMH compared to controls (0.7 ng/mL (IQR 0.2–1.7) vs 2.7 (IQR 1.3–4.8), p < 0.001). Additionally, girls with TXS were much more likely to have an AMH below the 2.5th percentile for age with 67% of them meeting these criteria (OR 11, 95% CI 2.3–42). Lower AMH concentrations in females with TXS may represent an increased risk for primary ovarian insufficiency in these patients and potentially a narrow window of opportunity to pursue fertility preservation options. Additional research is needed to understand the natural history of low AMH concentrations and future risk of premature ovarian insufficiency in girls with TXS.”

Rick Frith2021-01-15T14:37:59-05:00Categories: 47,XXX (trisomy x)|