Search

Klinefelter syndrome (KS) is the leading genetic cause of primary hypogonadism and infertility in men. The clinical phenotype has expanded beyond the original description of infertility, small testes, and gynecomastia. Animal models, epidemiologic studies, and clinical research of male subjects with KS throughout the lifespan have allowed the better characterization of the variable phenotype of this condition. This review provides an overview on what is known of the epidemiology, clinical features, and pathophysiology of KS, followed by a more focused discussion of testicular development and the clinical management of hypogonadism and fertility in boys and men with KS.

Hypokalemia is common during the treatment of diabetic ketoacidosis (DKA); however, severe hypokalemia at presentation prior to insulin treatment is exceedingly uncommon. A previously healthy 8-yr-old female presented with new onset type 1 diabetes mellitus, severe DKA (pH = 6.98), and profound hypokalemia (serum K = 1.3 mmol/L) accompanied by cardiac dysrhythmia. Insulin therapy was delayed for 9 h to allow replenishment of potassium to safe serum levels. Meticulous intensive care management resulted in complete recovery. This case highlights the importance of measuring serum potassium levels prior to initiating insulin therapy in DKA, judicious fluid and electrolyte management, as well as delaying and/or reducing insulin infusion rates in the setting of severe hypokalemia.

OBJECTIVE: Insulin is a commonly used, high-risk medication in the inpatient setting. Incorrect insulin administration can lead to preventable hypoglycemic events, which are a significant morbidity in inpatient diabetes care. The goal of this intervention was to decrease preventable insulin-related hypoglycemic events in an inpatient setting in a tertiary care pediatric hospital. METHODS: Methods included the institution of several interventions such as nursing and physician education, electronic medical record order sets, electronic communication note templates, and the development of new care guidelines. RESULTS: After the institution of multiple interventions, the rate of preventable hypoglycemic events decreased from 1.4 preventable events per 100 insulin days to 0.4 preventable events per 100 insulin days. CONCLUSIONS: Through the use of a multi-interventional approach with oversight of a multidisciplinary insulin safety committee, a sustained decreased rate of severe preventable hypoglycemic events in hospitalized pediatric patients receiving insulin was achieved.

Prior studies suggest a higher incidence of symptoms of attention-deficit/hyperactivity disorder in children with epilepsy, but few have investigated epilepsy in children with attention-deficit/hyperactivity disorder. Our objective was to compare the incidence and characteristics of epilepsy among population-based, research identified cohorts of children with (N=358) and without attention-deficit/hyperactivity disorder (N=728), based on medical record review to age 20. Data abstracted included characteristics of seizures, testing, and treatment. Cases were 2.7 times more likely to have epilepsy than controls (95% confidence interval 0.94–7.76; p=0.066), had earlier seizure onset (median age 5.5 versus 15 years; p=0.020), and a trend toward more frequent seizures (more than monthly, 63% versus 17%). Among children with attention-deficit/hyperactivity disorder, those with epilepsy tended to be less likely to have received a clinical diagnosis of attention-deficit/hyperactivity disorder (63% versus 89%; p=0.052) or to be treated with stimulants (50% verses 85%; p=0.025). Our findings suggest a strong trend towards a higher incidence of epilepsy among children with attention-deficit/hyperactivity disorder compared to those without. Epilepsy in children with attention-deficit/hyperactivity disorder appears to be more severe than in those without. Finally, there appears to be a reluctance to diagnose and initiate treatment for attention-deficit/hyperactivity disorder in children with epilepsy.

XXYY syndrome occurs in approximately 1:18,000–1:40,000 males. Although the physical phenotype is similar to 47,XXY (tall stature, hypergonadotropic hypogonadism, and infertility), XXYY is associated with additional medical problems and more significant neurodevelopmental and psychological features. We report on the results of a cross-sectional, multicenter study of 95 males age 1–55 with XXYY syndrome (mean age 14.9 years), describing diagnosis, physical features, medical problems, medications, and psychological features stratified by age groups. The mean age of diagnosis was 7.7 years. Developmental delays and behavioral problems were the most common primary indication for genetic testing (68.4%). Physical and facial features varied with age, although hypertelorism, clinodactyly, pes planus, and dental problems were common across all age groups. Tall stature was present in adolescents and adults, with a mean adult stature of 192.4 cm (SD 7.5; n = 22). Common medical problems included allergies and asthma (>50%), congenital heart defects (19.4%), radioulnar synostosis (17.2%), inguinal hernia and/or cryptorchidism (16.1%), and seizures (15%). Medical features in adulthood included hypogonadism (100%), DVT (18.2%), intention tremor (71%) and type II diabetes (18.2%). Brain MRI (n = 35) showed white matter abnormalities in 45.7% of patients and enlarged ventricles in 22.8%. Neurodevelopmental and psychological difficulties were a significant component of the behavioral phenotype, with developmental delays and learning disabilities universal but variable in severity. Twenty-six percent had full-scale IQs in the range of intellectual disability (MR), and adaptive functioning was significantly impacted with 68% with adaptive composite scores

Purpose of Study XXY syndrome (Klinefelter) and XXYY syndrome share a similar physical phenotype but differ in their behavioral phenotypes. Previous studies on XXY males describe academic difficulties and attentional problems, while reports of males with XXYY syndrome describe impulsivity, aggression, and anxiety. Despite multiple reports describing inattention, impulsivity, and behavioral problems in these groups, a study investigating the diagnosis of attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in XXY and XXYY patients has not yet been described. The purpose of this study is to (1) compare rates and subtypes of ADHD and ODD in XXY and XXYY syndromes and (2) to describe response of ADHD symptoms to psychopharmacologic treatment in these 2 groups. Methods Parents and teachers of males 5 to 25 years with XXY (n = 15) or XXYY (n = 24) completed the SNAP-IV rating scale that contains the DSM-IV criteria for ADHD and ODD. Clinical history and review of medication effectiveness were obtained by interview and record review. Results 33% of males (5/15) with XXY syndrome met criteria for ADHD. 80% met criteria for ADHD-Inattentive subtype while 20% met criteria for the Combined subtype. 2 of 15 males with XXY (13%) met criteria for ODD, and both also had ADHD. In comparison, 70% (17/24) with XXYY syndrome met criteria for ADHD. 50% of XXYY males with ADHD had the Combined subtype, while the other 50% had the Inattentive subtype. 11 of 24 XXYY male children (46%) also met diagnostic criteria for ODD. Clinical history was consistent with SNAP-IV responses in all patients. Psychopharmacologic treatment of ADHD with stimulants was effective in 65% of patients, although XXYY patients were more likely to need additional medications. Conclusions ADHD is an important clinical consideration in patients with both XXY and XXYY syndrome. Rates of ADHD of 33% in XXY and 70% in XXYY patients are considerably higher than the 3-10% reported in the general population and have not been previously reported in these patients. Males with XXY are more likely to have symptoms of inattention while XXYY males are more likely to have the combined subtype of ADHD. Males with XXYY are more likely to have ODD than XXY males. Stimulant treatment for ADHD symptoms is effective in both groups, and specific psychopharmacologic interventions will be discussed.

Objectives To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY). Study design Double-blind trial of 84 boys, ages 4-12 years, randomized to oxandrolone (Ox; 0.06 mg/kg daily; n = 43) or placebo (Pl; n = 41) for 24 months. Standardized assessments were performed at baseline and every 12 months for 24 months evaluating motor, cognitive, and behavioral function. Results The 24-month outcomes were better in the Ox vs. Pl group on 1 of 5 primary endpoints (motor function/strength): Bruininks Visual-Motor scale (P = .005), without significant differences between the 2 groups for the other 4 components. Secondary analyses suggested improvement in the Ox vs. Pl group in the anxiety/depression (P = .03) and social problems (P = .01) scales on the Child Behavior Checklist, anxiety (P = .04) on the Piers Harris Self Concept Scale, and interpersonal problems (P = .02) on the Children's Depression Inventory, without significant differences in hyperactive or aggressive behaviors. Conclusions This double-blind, randomized trial demonstrates that 24 months of childhood low-dose androgen treatment in boys with Klinefelter syndrome benefited 1 of 5 primary endpoints (visual-motor function). Secondary analyses demonstrated positive effects of androgen on aspects of psychosocial function (anxiety, depression, social problems), without significant effects on cognitive function, or hyperactive or aggressive behaviors. Trial registration ClinicalTrials.gov : NCT00348946 .

Klinefelter syndrome (KS) is a common condition in males, resulting in androgen deficiency and cardiometabolic diseases. These interrelated conditions may be present in prepubertal boys with KS.To determine whether supplemental low-dose androgen has a beneficial effect on body composition in prepubertal boys with KS.We conducted a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial in 93 boys with KS aged 4 to 12 years.Oral oxandrolone (Ox) 0.06 mg/kg/d or placebo for 2 years.The primary outcome was percent body fat standard deviation score (%BF SDS) at 2 years. Secondary outcomes included additional measures of cardiometabolic health and safety.The %BF SDS at 2 years was significantly lower in the treatment (0.29 ± 0.76 SDS) compared with placebo group (0.81 ± 0.72 SDS) after adjusting for age and baseline %BF SDS (95% confidence interval for the difference between means -0.86 to -0.19 SDS, P = 0.009). Ox resulted in lower triglycerides (P = 0.043), but also lower high-density lipoprotein (HDL) cholesterol (P0.001) and a more rapid advancement in bone age (P = 0.011).Ox has positive effects on measures of cardiometabolic health in prepubertal boys with KS; however, it does lower HDL cholesterol and advance bone age.

Objectif Les fonctions testiculaires des sujets avec syndrome de Klinefelter (1/600 hommes) sont mal connues dans l’enfance. Aussi avons-nous entrepris d’etudier leurs fonctions sertolienne et leydigienne en antepubertaire. Patients et methodes Au total, 93 garcons Klinefelter de 4–12 ans preleves chaque semestre pendant 2 ans. Mesure de FSH, LH, hormone anti-mullerienne(AMH), inhibineB(INHB) et testosterone. Resultats Initialement toutes les medianes sont dans les intervalles de reference, mais chez certains les taux s’ecartent des limites : 13 % ont des gonadotropines elevees des 4 ans, 31 % une inhibine B basse, 28 % une AMH elevee, 15 % une AMH basse. FSH, LH, et T sont correlees a l’âge (r = 0,31–0,37 ; p Conclusion Un deficit testiculaire precoce existe dans un sous-groupe de sujets Klinefelter, en relation avec un phenotype defavorable.

1005 Background: The prevalence of brain metastasis from breast cancer (BCA) is increasing. We have identified several potential therapeutic targets through gene expression profiling of human BCA brain metastases. One potential target, hexokinase II (HK-2), is up-regulated in brain metastases as compared to unlinked primary tumors. HK-2 plays a vital role in the generation of many components required for cell growth and inhibits apoptosis through mitochondrial binding. We hypothesized that HK-2 promotes metastatic cell proliferation in the brain and that its increased expression would negatively impact patient survival post-resection. Methods: The gene expression profile of surgically resected human BCA brain metastases was compared to that of non-related unlinked primary invasive ductal carcinomas using cDNA microarray analysis. In a separate retrospective study, we generated survival curves dividing a cohort of 113 patients based on HK-2 immunoreactivity in resected brain metastases. To evaluate the fun...

Purpose of Study XXY syndrome (Klinefelter9s syndrome) is the most common form of sex chromosome aneuploidy in males. Due to a similar physical phenotype, XXYY syndrome has traditionally been classified as a variant of Klinefelter9s syndrome. A study directly comparing the cognitive and behavioral features of these two syndromes has not been completed. The purpose of this study is to compare the cognitive and behavioral features of males with XXY syndrome to males with XXYY syndrome. Methods Patients were recruited from national organizations for patients with sex chromosome aneuploidy. All participants were males between the ages of 2.5 and 20 and had either XXY or XXYY karyotype. All families underwent a clinical interview and parents completed the Behavior Assessment System for Children (BASC). Cognitive testing was obtained using the WASI. Results The patient groups consisted of XXY males (n = 15) and XXYY males (n = 20). There were no significant differences in age between groups (mean age XXY = 9, XXYY = 12). Cognitive measures were compared between groups using t-tests, with statistically significant differences (p Conclusions XXYY males have Verbal and Full-Scale IQ9s significantly lower than males with XXY; however, their performance IQ does not significantly differ. XXYY males are more likely than XXY males to have problems with hyperactivity, aggression, conduct, atypicality, and depression. XXYY males also have significantly lower adaptive functioning than males with XXY syndrome. XXY males with lower IQs are more likely to have externalizing behavior, while IQ does not correlate with externalizing behaviors in XXYY syndrome. Although XXYY syndrome shares some physical features with XXY syndrome, XXYY syndrome appears to have a unique cognitive and behavioral profile and should be distinguished as its own behavioral phenotype.

Purpose of Study XXY syndrome (Klinefelter9s syndrome) is the most common form of sex chromosome aneuploidy in males. Due to a similar physical phenotype, XXYY syndrome has traditionally been classified as a variant of Klinefelter9s syndrome. A study directly comparing the cognitive and behavioral features of these two syndromes has not been completed. The purpose of this study is to compare the cognitive and behavioral features of males with XXY syndrome to males with XXYY syndrome. Methods Patients were recruited from national organizations for patients with sex chromosome aneuploidy. All participants were males between the ages of 2.5 and 20 and had either XXY or XXYY karyotype. All families underwent a clinical interview and parents completed the Behavior Assessment System for Children (BASC). Cognitive testing was obtained using the WASI. Results The patient groups consisted of XXY males (n = 15) and XXYY males (n = 20). There were no significant differences in age between groups (mean age XXY = 9, XXYY = 12). Cognitive measures were compared between groups using t-tests, with statistically significant differences (p Conclusions XXYY males have Verbal and Full-Scale IQ9s significantly lower than males with XXY; however, their performance IQ does not significantly differ. XXYY males are more likely than XXY males to have problems with hyperactivity, aggression, conduct, atypicality, and depression. XXYY males also have significantly lower adaptive functioning than males with XXY syndrome. XXY males with lower IQs are more likely to have externalizing behavior, while IQ does not correlate with externalizing behaviors in XXYY syndrome. Although XXYY syndrome shares some physical features with XXY syndrome, XXYY syndrome appears to have a unique cognitive and behavioral profile and should be distinguished as its own behavioral phenotype.

3678 Background: Metastatic disease is the hallmark of human malignancy that continues to challenge even the most recent advances in cancer treatment. In colorectal cancer, the major site of metastatic spread is the liver, but other sites include lung, and peritoneum, among others. In addition to elucidating mechanisms of tumor spread, predicting the pattern of metastatic spread could allow a more focused surveillance and adjuvant therapy. The aim of this study was to study the pattern of metastatic spread in colorectal cancer using gene expression micorarrays. Methods: Using microarrays consisting of ∼35,000 spotted oligonucleotides, we profiled 40 primary colorectal cancer samples from patients with resected primary tumors who developed metastatic disease. Patients were grouped into three patterns of isolated or dominant metastatic spread: liver, lung, and peritoneum/mesentery. Class comparison analysis and hierarchical clustering was performed on the array data. Results: An evident distinction could be...