American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献

Despite affecting in 1 in every 1000 females, remarkably little is known about trisomy X syndrome (47,XXX), especially among older adults who are undiagnosed. In this study, we aimed to determine the prevalence of 47,XXX among females enrolled in the Million Veterans Program (MVP; mean age 50.2 ± 13.6 years), and compare broad health outcomes between females with 47,XXX and 46,XX matched controls. We identified 61 females with an additional X chromosome, corresponding to a prevalence of 103 per 100,000 females; 27.9% had been clinically diagnosed. Females with 47,XXX had taller stature (+6.1 cm, p < 0.001), greater rate of outpatient encounters (p = 0.026), higher odds of kidney disease (odds ratio [OR] = 12.3; 95% confidence interval [CI] 2.9-51.8), glaucoma (OR = 5.1; 95% CI 1.5-13.9), and congestive heart failure (OR = 5.6; 95% CI 1.4-24.2), and were more likely to be unemployed (p = 0.008) with lower annual income (p = 0.021) when compared with 46,XX controls of the same age and genetic ancestry. However, there were no differences in the rates of other encounter types, Charlson Comorbidity Index, all other medical and psychological diagnoses, military service history or quality of life metrics. In conclusion, in this aging and predominately undiagnosed sample, 47,XXX conferred few differences when compared with matched controls, offering a more reassuring perspective to the trisomy X literature.

The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de-identified clinical information and multi-omics data from research participants for broad data sharing and secondary analyses. Through the DS-Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan.

Code status is a label in the medical record indicating a patient's wishes for end-of-life (EOL) care in the event of a cardiopulmonary arrest. People with intellectual disabilities had a higher risk of both diagnosis and mortality from coronavirus infections (COVID-19) than the general population. Clinicians and disability advocates raised concerns that bias, diagnostic overshadowing, and ableism could impact the allocation of code status and treatment options, for patients with intellectual disabilities, including Down syndrome (DS). To study this, retrospective claims data from the Vizient® Clinical Data Base (used with permission of Vizient, all rights reserved.) of inpatient encounters with pneumonia (PNA) and/or COVID-19 at 825 hospitals from January 2019 to June 2022 were included. Claims data was analyzed for risk of mortality and risk of “Do Not Resuscitate” (DNR) status upon admission, considering patient age, admission source, Elixhauser comorbidities (excluding behavioral health), and DS. Logistic regression models with backward selection were created. In total, 1,739,549 inpatient encounters with diagnoses of COVID-19, PNA, or both were included. After controlling for other risk factors, a person with a diagnosis of DS and a diagnosis of COVID-19 PNA had 6.321 odds ratio of having a DNR status ordered at admission to the hospital compared with those with COVID-19 PNA without DS. The diagnosis of DS had the strongest association with DNR status after controlling for other risk factors. Open and honest discussions among healthcare professionals to foster equitable approaches to EOL care and code status are needed.

Down syndrome (DS) is associated with multiple medical comorbidities. Perhaps related to such, caregivers of individuals with DS report lower quality of life (QoL) compared to individuals without DS. It has been shown that disorders of gut-brain interaction (DGBI) such as functional constipation (FC) and irritable bowel syndrome (IBS) are common in individuals with DS. We measured caregiver-reported QoL in individuals with DS with a DGBI and compared them to individuals with DS without a DGBI via a cross-sectional national survey. All measures of QoL were lower in those with DS who meet criteria for a DGBI compared to those with DS without a DGBI. Males and females with DS and at least one DGBI had similar QoL scores. While FC was the most common DGBI seen in individuals with DS, there was no difference in any aspect of QoL in subjects with FC when compared to individuals with other DGBIs. However, all measures of QoL were lower in those with IBS compared to individuals with other DGBIs. These findings suggest that management of gastrointestinal symptoms from DGBIs, particularly IBS, may serve as a target for increasing QoL in a notable subset of individuals with DS.

Objective: Children with Down syndrome (DS) may experience changes in sleep architecture (i.e., different sleep stages) that then affect waketime functioning, including learning, mood, and disruptive behavior. For designing and testing interventions, it is important to document any differences in sleep architecture in children with DS with and without co-occurring diagnoses, including neuropsychiatric diagnoses and obstructive sleep apnea (OSA).

Methods: A retrospective cohort study was performed at Massachusetts General Hospital for children and adolescents with DS who underwent polysomnography (PSG) between August 2016 and July 2022. Patient data collected from the electronic medical record included diagnoses, age at PSG, and PSG report. Statistical analysis included unpaired T tests to test hypotheses about differences in sleep architecture within age groups, and differences between children with DS and a co-occurring diagnosis. One way ANOVA was used to determine statistical significance of OSA severity within patients with DS.

Results: When compared by age group, those with DS had negative changes in sleep architecture (e.g., less sleep and more wake) when compared to normative data. Within this cohort, having a co-occurring diagnosis of autism resulted in further, negative effects on sleep architecture. 89% of those with DS had diagnosed OSA but only those with severe OSA experienced negative effects on sleep architecture.

Conclusion: Age is an important covariate when studying the sleep of children with DS and neurotypical children. Studies are needed to test whether minimizing the observed differences in sleep architecture will translate to improved learning, mood, and behavioral outcomes, and how treating OSA affects sleep architecture.

Down syndrome (DS) and other genetic conditions have been reported to co-occur in the same person. This study sought to examine the genetic evaluation beyond chromosome analysis of individuals with DS at one DS specialty clinic. Retrospective chart review of genetic testing performed beyond chromosome analysis, the indication for the genetic testing, and the result of the genetic testing from the electronic health record was performed. Demographic information was collected and summary statistics, including mean and frequency, were calculated. The charts of 637 individuals with DS were reviewed. Overall, 146 genetic tests in addition to routine chromosome analysis were performed on 92 individuals with DS. Tests included chromosomal microarray, gene panels, and whole exome sequencing. Tests were performed for the indication of: autism spectrum disorder, celiac disease, dementia, hematologic diseases, and others. Eleven individuals with DS were found to have a second genetic diagnosis. Individuals with DS in one multidisciplinary clinic for DS had a variety of genetic tests beyond chromosomes completed, for varied indications, and with some abnormal results leading to additional diagnoses. Additional genetic testing beyond chromosome analysis is a reasonable consideration for patients with DS who have features suggestive of a secondary diagnosis.

We report the case of an 18-year-old woman with Down syndrome (DS) who developed Takotsubo cardiomyopathy (TSC) immediately after the administration of electroconvulsive therapy (ECT), a treatment prescribed for Down syndrome regression disorder resistant to oral psychotropic drugs. TSC is a nonischemic cardiomyopathy related to psychological or physical stress, which has been described as a rare complication of ECT (Kinoshita et al., 2023, Journal of Electroconvulsive Therapy, 39, 185–192). The clinical description of the case is accompanied by a discussion of the peculiarities of the autonomic nervous system in DS.

Individuals with Down syndrome (DS) have been particularly impacted by respiratory conditions, such as pneumonia. However, the description of co-occurring recurrent infections, the response to pneumococcal immunization, and the association of these was previously unknown. We screened individuals with DS using an 11-item screener and prospectively collected pneumococcal titers and laboratory results. We found that the screener did not successfully predict which individuals with DS who would have inadequate pneumococcal titers. Thirty four of the 55 individuals with DS (62%) had abnormal pneumococcal titers demonstrating an inadequate response to routine immunization. In the absence of a valid screener, clinicians should consider screening all individuals with DS through the use of pneumococcal titers to 23 serotypes to assess vaccine response.