49,XXXXY syndrome: A study of neurological function in this uncommon X and Y chromosomal disorder.

49,XXXXY is a rare chromosomal variation characterized by deficits in motor, language, and cognitive domains. This study reports on the neurological function and dysmorphic features in the largest cohort to date. Seventy-two boys with 49,XXXXY were evaluated on a variety of domains including a neurological examination and neuromotor assessments including the Beery Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Results supported previous literature by describing high occurrences of truncal and extremity hypotonia, which significantly impacts on motor milestones and ambulation in this population. The boys presented with dysmorphic features including epicanthal folds, frontal bossing, and synophrys. Visual perception skills were mildly impaired and cranial nerves were typically intact, however capabilities in motor coordination and fine motor precision were greatly delayed, supporting deficits in refined and controlled hand movements versus widespread visual deficits. Preschool boys treated with testosterone replacement had significantly increased scores when compared to the untreated group on the BSID-III Psychomotor Development Index, further supporting previous research indicating that testosterone replacement may have a positive impact on neurodevelopmental outcomes in males with additional X chromosomes. Boys with 49,XXXXY may benefit from hormonal treatment in conjunction with early intervention services to address their significant motor deficits.

Neurocognitive development and capabilities in boys with 49,XXXXY syndrome.

49,XXXXY was previously associated with profound to severe intellectual deficits. However, prior research papers on the cognitive profiles of this population were confounded by small samples sizes, wide age spreads, and incomplete histories of testosterone replacement therapy. This study is the first comprehensive, international investigation of the neurocognitive aspects of 49,XXXXY, and the potential effects of biological treatment on this profile. Sixty-seven boys from infancy to 11 years of age were enrolled in this longitudinal study, with the majority of boys postnatally diagnosed though chromosomal analysis. These boys received a comprehensive neurocognitive evaluation tailored to specific language-based deficits and cognitive challenges. Results revealed higher neurocognitive capacities, both verbally and nonverbally, than previously reported in this disorder. Infant boys with 49,XXXXY who received early hormonal therapy (EHT) had significantly higher scores on the cognitive domain of the Bayley Scales of Infant Development than untreated infants (p = .013). In addition, treated school-aged participants had significantly better scaled scores than untreated boys in form completion (p = .042), a task that requires deductive reasoning, on nonverbal testing on the Leiter International Performance Scales. This study indicates greater cognitive capacities with a wide range of abilities in the child with 49,XXXXY, thus warranting further investigation to identify and understand the critical influences on the etiology and the variability of those capacities.

Speech and language development in children with 49,XXXXY syndrome.

49,XXXXY is the rarest X and Y chromosomal variation and is frequently characterized by expressive and receptive language dysfunction, low muscle tonus, and intellectual deficits. Due to the low incidence of this disorder, comprehensive studies analyzing the specific aspects of the speech and language phenotype in these boys have been uncommon. This is the first in-depth investigation of the speech and language profiles in a large cohort of boys with 49,XXXXY. Based on the clinical judgment of speech and language pathologists, there was an increased incidence (91.8%) of Childhood Apraxia of Speech (CAS), which has not been previously described in this disorder. In preschool boys, some significant differences were demonstrated between boys who received early hormonal treatment (n = 16) and untreated boys (n = 4) on the language scales (p = .047) on the Bayley Scales of Infants and Toddlers, as well as significant differences between treated (n = 13) and untreated boys (n = 8) on the Expressive One Word Picture Vocabulary Test (p = .008). No significant differences between treatment groups were found in school age children, however, treated groups demonstrated less discrepancies between expressive and receptive language. More research and larger samples are needed to determine the extent of the impact of testosterone treatment on boys with 49,XXXXY. This study identifies CAS as a potential explanation for the significant expressive language dysfunction and subsequent behavioral dysfunction. These findings may assist in facilitating more targeted treatment and improved outcomes for boys with 49,XXXXY.

Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Behavioral phenotype of 49,XXXXY syndrome: Presence of anxiety-related symptoms and intact social awareness.

49,XXXXY is a rare X and Y chromosome variation that occurs in 1:85,000 to 1:100,000 live male births and is notable for variable motor, speech, and behavioral deficits. Case studies have described boys with this disorder as shy, impulsive, and aggressive with low frustration tolerances; however, previous studies have been limited due to cohort size. This study reports on the largest cohort of boys with 49,XXXXY to date with an emphasis on the prevalence of anxiety-related symptoms and sociability from preschool to adolescence. The Child Behavior Checklist, Behavior Rating Inventory of Executive Function, 2nd edition, and Social Responsiveness Scale, 2nd edition were completed by parents on a cohort of 69. The cohort demonstrated deficits in social cognition and communication beginning in preschool, however, presented with consistent social awareness and motivation for social activities not previously appreciated in this disorder. In addition, signs of anxiety presented during preschool years and increased in severity with age, particularly in internalizing problems. Boys with 49,XXXXY presented with wide behavioral variability across all ages and domains. Further research into the potential influences of culture, birth order, biological treatment, and frequency of services is needed to better define the behavioral phenotype of children with this disorder.

A review of the intriguing interaction between testosterone and neurocognitive development in males with 47,XXY.

PURPOSE OF REVIEW: Although 47,XXY (Klinefelter syndrome) was first discovered more than 50 years ago, there have been limited comprehensive studies on this disorder. The present review explains the study of neurodevelopmental dysfunction and the impact of testosterone replacement at specific junctions in the life of males with 47,XXY. The intricate relationship between testosterone, neurodevelopment, health, and well being warrants an in-depth investigation in order to achieve optimal outcomes. RECENT FINDINGS: Current literature suggests that the implementation of biological treatment has a positive impact on numerous areas of neurodevelopment. Further research is needed to determine ideal dosage, timing, and frequency of biological treatment for efficacy and safety of the child with 47,XXY. SUMMARY: As noninvasive prenatal screening has detected increasing numbers of fetuses with 47,XXY, parents may benefit from both prenatal and postnatal counseling, including the latest innovative biological treatment, that may further optimize the child's outcome, especially when coupled with targeted early intervention services.

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

OBJECTIVE: To investigate the attitudes of parents of children with a sex chromosome aneuploidy (SCA) regarding the impact of an early diagnosis and noninvasive prenatal testing (NIPT). METHOD: A survey consisting of multiple choice and long response formatted questions was completed by parents of children with SCA(s). RESULTS: Fifty-five participants responded to the survey. A total of 88.1% of participants who received an early diagnosis expressed that it had a positive impact on their child's life. Of the 23 participants who utilized NIPT, 95.7% believed it was a decisive factor in their life because they could research the disorders prior to the birth of their child (35.3%), pinpoint valuable resources and interventions (38.2%), and determine possible risk factors of neurodevelopmental delays to be considered after delivery (20.6%). CONCLUSION: This study documented parental perspectives on the impact of an early SCA diagnosis and attitudes towards NIPT use for identifying those at risk for SCAs. These informative and insightful results provide personal experiences that health care providers may want to consider when providing prenatal counseling on NIPT for expectant mothers. As this analysis is the first of its kind, ascertainment is limited, and future research should aim to expand these findings by investigating the different factors influencing attitudes towards NIPT.

Investigating links between creativity anxiety, creative performance, and state-level anxiety and effort during creative thinking.

Identifying ways to enable people to reach their creative potential is a core goal of creativity research with implications for education and professional attainment. Recently, we identified a potential barrier to creative achievement: creativity anxiety (i.e., anxiety specific to creative thinking). Initial work found that creativity anxiety is associated with fewer real-world creative achievements. However, the more proximal impacts of creativity anxiety remain unexplored. In particular, understanding how to overcome creativity anxiety requires understanding how creativity anxiety may or may not impact creative cognitive performance, and how it may relate to state-level anxiety and effort while completing creative tasks. The present study sought to address this gap by measuring creativity anxiety alongside several measures of creative performance, while concurrently surveying state-level anxiety and effort. Results indicated that creativity anxiety was, indeed, predictive of poor creative performance, but only on some of the tasks included. We also found that creativity anxiety predicted both state anxiety and effort during creative performance. Interestingly, state anxiety and effort did not explain the associations between creativity anxiety and creative performance. Together, this work suggests that creativity anxiety can often be overcome in the performance of creative tasks, but likewise points to increased state anxiety and effort as factors that may make creative performance and achievement fragile in more demanding real-world contexts.

What Makes Mental Modeling Difficult? Normative Data for the Multidimensional Relational Reasoning Task.

Relational reasoning is a complex form of human cognition involving the evaluation of relations between mental representations of information. Prior studies have modified stimulus properties of relational reasoning problems and examined differences in difficulty between different problem types. While subsets of these stimulus properties have been addressed in separate studies, there has not been a comprehensive study, to our knowledge, which investigates all of these properties in the same set of stimuli. This investigative gap has resulted in different findings across studies which vary in task design, making it challenging to determine what stimulus properties make relational reasoning-and the putative formation of mental models underlying reasoning-difficult. In this article, we present the Multidimensional Relational Reasoning Task (MRRT), a task which systematically varied an array of stimulus properties within a single set of relational reasoning problems. Using a mixed-effects framework, we demonstrate that reasoning problems containing a greater number of the premises as well as multidimensional relations led to greater task difficulty. The MRRT has been made publicly available for use in future research, along with normative data regarding the relative difficulty of each problem.

Update On The Clinical Perspectives And Care Of The Child With 47,XXY (Klinefelter Syndrome).

47,XXY (Klinefelter syndrome [KS]) is the most common sex chromosomal aneuploidy (1:660), yet, despite this, only 25% of the males are ever diagnosed. Males with 47,XXY present with characteristic symptoms throughout their lifetime with typical physical and neurodevelopmental manifestations focused in growth, cognitive development, endocrine function, and reproduction. Studies have demonstrated that optimal outcomes are dependent on early detection combined with consistent and targeted neurodevelopmental treatment throughout the lifespan. During infancy and into the preschool years, individuals with 47,XXY commonly face deficits in growth and development in the areas of early hormonal, motor, speech, and behavioral development. As they transition into school, the primary neurodevelopmental concerns include language difficulty, executive dysfunction, behavior, and learning and reading deficits. Adults with 47,XXY often present with taller than average height, low levels of fertility, azoospermia, and elevated gonadotropin levels. These presentations may persist from early childhood through adulthood but can be mitigated by appropriate interventions. Early neurodevelopmental and hormonal treatment has been shown to have a minimizing effect on the physical and neurodevelopmental manifestations in individuals with 47,XXY. With innovative and current research studies, the features common to the neurodevelopmental profile of 47,XXY have been further expanded and defined. Further research is necessary to elucidate and understand the relationship between the brain, behavior, and the phenotypic profile of 47,XXY.