The Effect of Hormonal Therapy on the Behavioral Outcomes in 47,XXY (Klinefelter Syndrome) between 7 and 12 Years of Age

47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal aneuploidy (SCA). Hormonal replacement therapy (HRT) has been associated with improved neurodevelopmental capabilities in boys with 47,XXY, although studies investigating HRT\u27s possible positive effect on behavioral outcomes are scarce. This study explores the association between behavioral outcomes and HRT in boys ages 7-12. Patients were divided into 4 groups based on HRT status: untreated, early hormonal treatment (EHT), hormonal booster therapy (HBT), and both EHT and HBT. Analysis of Variance (ANOVA) and Kruskal-Wallis tests were conducted to determine group differences on the Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF). The treated groups were found to have better scores in emotional control, initiative, organization of materials, behavioral rating index, metacognition index, and global executive composite than the untreated group on the BRIEF. On the CBCL, the treated groups presented better scores for somatic complaints, social problems, thought problems, attention problems, aggressive behavior, internalizing problems, total problems, affective problems, somatic problems, ADHD problems, oppositional defiant problems, and sluggish problems in comparison to the untreated group. These results offer evidence that HRT, specifically the combination of both EHT and HBT, may be successful in mitigating some undesirable behavioral outcomes. Further research is necessary to determine the efficacy of the combination of EHT and HBT regarding dosage, specific ages, and long-term benefits

Novel Neurocognitive Profile in a Minority of Boys with 47,XXY (Klinefelter Syndrome)

INTRODUCTION: 47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal variation (1:660). The neurocognitive profile of boys with 47,XXY, in addition to verbal abilities, language skills, and general intelligence, has been explored in this study. METHODS: Fifty-five participants with 47,XXY were segregated into groups according to their performance on the Wechsler Intelligence Scale for Children (WISC): (1) those with a higher performance intelligence quotient (PIQ) in comparison with their verbal IQ (VIQ) and (2) those with a higher VIQ compared with their PIQ. Two-tailed independent t tests were completed to analyze group differences. RESULTS: Our study results demonstrate novel findings that one-third of subjects have higher verbal capabilities than perceptual skills. Those participants who showed the typical presentation of 47,XXY with increased PIQ in comparison with their VIQ excelled on perceptual and visual spatial subtests on the WISC and on nonverbal IQ on the Leiter International Performance Scale-III. In addition, it was found that expressive and receptive vocabulary skills were commensurate in both groups, which has not been reported previously. DISCUSSION: To the best of our knowledge, this is the first study to identify an alternative profile of 47,XXY with increased verbal capabilities in comparison with perceptual skills. In addition, previous research has found that boys with 47,XXY often show increased receptive vocabulary skills in comparison with their expressive vocabulary skills early in life. Therefore, our findings of commensurate expressive and receptive vocabulary skills suggest that age may be an impactful factor in vocabulary development. Further research is necessary to determine individualized treatment options for these patients, focusing on the specific cognitive profile they present

THERAPEUTIC APPROACH TO A CHILD WITH ACUTE RESPIRATORY DISTRESS SYNDROME: A REPORT OF TWO CASES

The course of a respiratory disorder in a child may end up in respiratory failure. There are also acute non-respiratory diseases which have a great influence on the respiratory functions and often lead to the acute lung injury and sometimes to the acute respiratory distress syndrome (ARDS). A feature of respiratory function deterioration is changed in the surfactant system. We often see inhibition of its synthesis or damage to its structure. Therapy of children suffering from ARDS should be complex and rapid. Despite many recently published studies explaining the principle of this disorder, the mortality of ARDS is still very high (30-50%). There are several studies documenting successful administration of exogenous surfactant as part of a complex combined therapy of patients with ARDS, which leads to decreased mortality, improved oxygenation, and decreased need for aggressive artificial pulmonary ventilation. The authors of this article present their own experience with administration of exogenous surfactant in therapy of children with ARDS

The behavioral profile of 49,XXXXY and the potential impact of testosterone replacement therapy

PURPOSE: 49,XXXXY (1:85,000-100,000) is a rare sex chromosome aneuploidy that often presents with complex musculoskeletal abnormalities, decreased cognitive capabilities, speech and language dysfunction, and behavioral complications. Hormonal replacement therapy, or testosterone replacement therapy, is associated with improved neurodevelopmental and behavioral outcomes in males with 49,XXXXY. Two forms of testosterone replacement therapy, early hormonal treatment (EHT) and hormonal booster therapy (HBT), are associated with improved neurodevelopmental and behavioral outcomes in these boys. This study investigates the impact of EHT and HBT on behavioral symptoms in males with 49,XXXXY. METHODS: A total of 59 individuals were divided into 4 groups: 19 no testosterone (no-T), 23 EHT, 6 HBT, and 11 EHT and HBT. An analysis of variance examined group differences on the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function ranging from 5 to 18 years. RESULTS: Although no differences were identified on the Behavior Rating Inventory of Executive Function, the 3 hormonal replacement therapy groups presented with decreased complications on numerous variables on the Child Behavior Checklist; these include somatic complaints (P = .0095), somatic problems (P = .041), internalizing problems (P = .034), externalizing problems (P = .0001), and withdrawn/depression (P = .025). CONCLUSION: This study presents evidence that HBT may be a beneficial treatment for individuals with 49,XXXXY

Case Report: Infant With Congenital Adrenal Hyperplasia and 47,XXY

Congenital adrenal hyperplasia is a group of autosomal recessive disorders in which enzymes in the cortisol biosynthesis pathways are disrupted by gene mutations. The most common form of congenital adrenal hyperplasia, caused by 21-hydroxylase deficiency, is characterized by decreased cortisol and aldosterone synthesis and excessive androgen production. Adult height is often compromised in affected patients. Intellectual capability remains intact in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, based on previous studies. 47,XXY (KS) is a sex chromosomal aneuploidy that manifests with hypergonadotropic hypogonadism, tall stature, and variable intellectual and behavioral dysfunction. This clinical report describes an infant with 21-hydroxylase deficiency congenital adrenal hyperplasia and 47,XXY. The results of his neurodevelopmental, endocrine, neurological, and physical therapy evaluations during his first 22 months are included and were normal. This is the first published case investigating the neurodevelopmental profile of a patient with the combination of these two genetic disorders

Incidence of sex chromosome aneuploidy in Northern Italy: 27-year longitudinal study

OBJECTIVES: The availability of cell-free DNA (cfDNA) as a screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidies (SCAs). This longitudinal study from 1995 through 2021 investigates both the evolution and frequency of prenatal diagnostic testing using amniocentesis (AF) and chorionic villus sampling (CV), and the detection of SCAs through cfDNA samples from a large cohort in Northern Italy. METHODS: The results of genetic testing from CV and AF samples collected from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCAs and correlated with changes in the indications for prenatal diagnostic tests and available screening options. RESULTS: In 27 years, 13,939,526 births and 231,227 invasive procedures were performed. This resulted in the prenatal diagnosis of 934 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures significantly decreased (P=0.03), while the frequency of prenatal SCA detection significantly increased (P=0.007). The indication for invasive procedures also shifted from advanced maternal age (AMA) to positive cfDNA results for sex chromosome trisomies (SCTs). CONCLUSIONS: Our findings suggest the inclusion of SCAs in prenatal cfDNA screening tests can increase the prenatal identification of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. This article is protected by copyright. All rights reserved