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While the most common Sex Chromosome Aneuploidy (SCA) is 47,XXY, other variations, such as 48,XXYY, are less studied, perhaps due to its rarity. 48,XXYY occurs with an estimated prevalence of 1:18,000-40,000 male births. This SCA is associated with a variety of complex physical, psychological, and neuroanatomical findings. The purpose of this integrative review is to summarize the available evidence related to 48,XXYY and identify gaps in the literature. This study utilized integrative review and PRISMA-guided methodology to search six databases for information pertaining to 48,XXYY. There were no exclusion criteria related to design methodology, given the paucity of available research. Among 397 articles reviewed for potential inclusion, 30 articles remained after inclusion and exclusion criteria were applied. Seven of these articles concentrated solely on participants with 48,XXYY. Literature was summarized into categories of physical phenotype, psychosocial, behavioral, neurocognitive, and brain function. Clinical description of 48,XXYY has evolved over time to develop a deeper understanding of this complex disorder. Large gaps remain, especially a lack of experimental studies, clinical guidelines, and treatments. Additionally, few studies explore methodologies such as interviews or self-report surveys in this population. 48,XXYY presents with a wide spectrum of physical, psychological, and neurocognitive symptoms, and frequently requires complex interdisciplinary care. In order to better understand this disorder and to appropriately treat the individuals affected by it, future research should focus on experimental studies and research that utilizes a variety of methods, including participant interviews and patient-report surveys.

A large number of adults and children consume soy in various forms, but little information is available regarding potential neurological side effects. Prior work indicates an association between the consumption of soy-based diets and seizure prevalence in mouse models of neurological disease and in children with autism. Herein, we sought to evaluate potential associations between the consumption of soy-based formula during infancy and disease comorbidities in persons with fragile X syndrome (FXS), while controlling for potentially confounding issues, through a retrospective case-control survey study of participants with FXS enrolled in the Fragile X Online Registry with Accessible Research Database (FORWARD). There was a 25% usage rate of soy-based infant formula in the study population. We found significant associations between the consumption of soy-based infant formula and the comorbidity of autism, gastrointestinal problems (GI) and allergies. Specifically, there was a 1.5-fold higher prevalence of autism, 1.9-fold GI problems and 1.7-fold allergies in participants reporting the use of soy-based infant formula. The major reason for starting soy-based infant formula was GI problems. The average age of seizure and allergy onset occurred long after the use of soy-based infant formula. We conclude that early-life feeding with soy-based infant formula is associated with the development of several disease comorbidities in FXS.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

Author(s): Hendrix, James; Burke, Anna D; Capone, George; Chicoine, Brian; Costa, Alberto; Esbensen, Anna J; Hart, Sarah J; Head, Elizabeth; Kishnani, Priya S; Lai, Florence; Lott, Ira T; Ochoa-Lubinoff, Cesar; Rosas, H Diana; Rosser, Tracie; Santoro, Stephanie L; Schmitt, Frederick A; Sherman, Stephanie; Skotko, Brian G; Talboy, Amy L; Woodward, Jason; Feldman, Howard H; Revta, Carolyn; Schafer, Kimberly A; Hillerstrom, Hampus; Mobley, William

47,XXY (Klinefelter Syndrome) is associated with a spectrum of complex clinical needs that are associated with variable physical, neurocognitive and psychosocial aspects. For patients and families affected by this sex chromosome trisomy, navigation of health care services is difficult due to lack of 47,XXY awareness among many health care providers and little evidence to support endocrine and additional treatment plans. While endocrine management of androgen deficiency has been the mainstay of treatment for patients from puberty through adulthood, testosterone replacement, alone, fails to mitigate many symptoms and issues. Prior to the onset of puberty, boys with 47,XXY often do not receive interdisciplinary evaluations and treatment. Since multiple health and ancillary therapeutic services are required for the management of 47,XXY, patients and families often experience disjointed and uncoordinated care. We discuss complexities of caring for patients with 47,XXY and the benefit of integrating advanced practice nursing and medical perspectives to improve care delivery.