The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy

Abstract

Funding informationThe Focus Foundation 47,XXY (Klinefelter syndrome) is the most common X and Y chromosomal variation (1:660 males). The incidence of anxiety disorders and the impact of hormonal replacement therapy (HRT) is not well understood. Child Behavior Checklist and Screen for Childhood Anxiety Related Emotional Disorders were completed by parents of 80 boys with 47,XXY. Forty received HRT prior to 10 years of age while 40 did not. HRT (22.5%) received early hormonal treatment prior to 18 months. About 32.5% received hormone booster treatment between 5 and 10 years. The remaining 42.5% received both. There were fewer reported social (p = .015), thought (p = .012), and affective problems (p = .048) in treated boys when compared to untreated. Boys with both treatments demonstrated fewer symptoms on anxious/depressed scale (p = .001) compared to those with early treatment only. Within the treated group, prenatally diagnosed showed fewer indications of anxiety problems (p = .02) than their postnatal counterparts. This comparative, cross-sectional study expands previous findings on the possible positive effect of HRT in boys with 47,XXY. Anxiety disorders appear to be a penetrant aspect of the 47,XXY phenotype. Further investigation is warranted to explore the relationship between biological treatment and individual responses to HRT to develop more personalized and precise medicine. K E Y W O R D S anxiety disorders, hormonal replacement therapy, Klinefelter syndrome, sex chromosome abnormalities and aneuploidies, X and Y chromosomal variations, 47,XXY

Impact of early diagnosis and noninvasive prenatal testing (NIPT): Knowledge, attitudes, and experiences of parents of children with sex chromosome aneuploidies (SCAs)

“…Children with these disorders present with dysfunction in speech, language, and motor development . The phenotype spans a wide range of associated symptoms that vary in severity depending on the specific SCA, timing of diagnosis, and family history …”

“…Over 50 years of publications have demonstrated significant evidence to the importance of early identification of SCAs and the positive impact of early intervention on neurodevelopmental outcomes . These studies have also shown that children prenatally diagnosed with an SCA have less neurodevelopmental dysfunction, fewer behavioral disturbances, and IQs within or above the normal limits.…”

“…These studies have also shown that children prenatally diagnosed with an SCA have less neurodevelopmental dysfunction, fewer behavioral disturbances, and IQs within or above the normal limits. Families with children prenatally diagnosed with an SCA were less likely to see deficits and had relatively unaffected or mildly affected children . With a prenatal diagnosis, the option of proactive implementation of interventions, such as speech therapy, physical therapy, and hormonal replacement therapy for boys with additive X chromosomes, becomes available earlier and provides the opportunity for the patient to seek treatment before development has become significantly delayed …”

“…[3][4][5][6][7][8][9] The phenotype spans a wide range of associated symptoms that vary in severity depending on the specific SCA, timing of diagnosis, and family history. 7,8,[10][11][12][13] Because of the lack of characteristic and unusual physical features in 47,XXY (Klinefelter syndrome, KS), and 47,XYY, the rate of diagnosis remains markedly diminished, despite estimated incidence rates of one in 660 and one in 1000, respectively. 2,14,15 The features common to these disorders include pes planus, clinodactyly, taller than average stature, hypotonia, speech and language delays, and language-based learning disorders (LLDs).…”

“…Families with children prenatally diagnosed with an SCA were less likely to see deficits and had relatively unaffected or mildly affected children. 9,12,13,34 With a prenatal diagnosis, the option of proactive implementation of interventions, such as speech therapy, physical therapy, and hormonal replacement therapy for boys with additive X chromosomes, becomes available earlier and provides the opportunity for the patient to seek treatment before development has become significantly delayed. 9 Invasive procedures for prenatal testing such as amniocentesis and chorionic villus sampling (CVS) were created as diagnostic options for high-risk mothers because of advanced maternal age or a family history of genetic disorders.…”