Sandra L. Friedman

Deletions of NRXN1 (Neurexin-1) Predispose to a Wide Spectrum of Developmental Disorders

Research has implicated mutations in the gene for neurexin‐1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 × 10−7). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.

Neurodevelopmental outcomes of congenital diaphragmatic hernia survivors followed in a multidisciplinary clinic at ages 1 and 3

PURPOSE Infants who survive congenital diaphragmatic hernia (CDH) repair may have ongoing medical and neurodevelopmental morbidity after hospital discharge. We evaluated the relationship between medical and neurodevelopmental outcomes of CDH survivors seen in a multidisciplinary clinic at ages 1 and/or 3. METHODS From January 1997 to December 2004, 69 (61%) of 112 CDH survivors were followed in our CDH clinic at ages 1 and/or 3. Medical issues (cardiac, pulmonary, gastrointestinal) were tabulated at hospital discharge and at follow-up. Neurodevelopmental data were obtained from clinic assessments by a neurodevelopmental pediatrician. Descriptive results were summarized for each cohort. Multivariate analyses were performed to identify predictors of motor problems at age 1. RESULTS Of the 69 study participants, 64% were male, 75% had left-sided CDH, 17% had cardiac anomalies, and 25% had other congenital malformations. Nearly all required ventilator management (99%) with a median ventilator time of 14 days (range, 1-54 days); 30% required extracorporeal membrane oxygenation. While 87% of patients had medical issues at hospital discharge, 61% and 67% had medical issues at ages 1 and 3, respectively. Pulmonary problems were noted in 34% and 33% of the ages 1 and 3 cohorts, respectively. Motor and language problems were detected in 60% and 18% of the age 1 cohort and 73% and 60% of the age 3 cohort, respectively. Multivariate analysis found ventilator time as the only independent predictor of motor problems at age 1 (odds ratio, 1.12 per day; 95% confidence interval, 1.05-1.20; P < .01). CONCLUSIONS Young CDH survivors continue to have ongoing medical problems and a high incidence of motor and language problems. Duration of neonatal ventilatory support was a significant predictor of motor problems at age 1. Prospective studies are needed to confirm these findings.

Unique and universal barriers: hospice care for aging adults with intellectual disability.

As life expectancy of people with intellectual disability (ID) has increased, there has been a concurrent increase in age-related illnesses and conditions similar to that of the general population. These circumstances result in people with ID dying from typical life-ending conditions, and thus, they require similar end-of-life services such as palliative and hospice care. Although there are notable barriers to hospice for all, people with ID face additional challenges in accessing the benefits of these services. This article presents a review of the literature on these issues, underscoring the multiple challenges and the importance of a more collaborative approach between hospice and palliative care workers with people with ID, their families, and other important stakeholders.

Abnormal neuroimaging and neurodevelopmental findings in a cohort of antenatally diagnosed congenital diaphragmatic hernia survivors

PURPOSE Prior studies have shown that survivors of congenital diaphragmatic hernia (CDH) repair may have long-term cardiac, pulmonary, and nutritional issues, as well as neurodevelopmental sequelae within the first 3 years of life. In this study, we examined the relationship between neuroimaging abnormalities and neurodevelopmental outcomes in a cohort of antenatally diagnosed CDH survivors. METHODS Retrospective chart reviews were performed for CDH survivors born from January 2000 to December 2007 who were evaluated antenatally in the Advanced Fetal Care Center at Childrens Hospital Boston (Mass). Prenatal and postnatal neuroimaging findings, clinical data, and neurodevelopmental findings were collected for a cohort of 45 patients who were evaluated by a developmental pediatrician at ages 1 and/or 3. RESULTS Prenatal neuroimaging studies detected brain anomalies in this cohort with a false-negative rate of 7%. Of the 45 study participants, 87% had left-sided CDH, 22% had cardiac anomalies, and 18% had congenital malformations or genetic syndromes. Nearly all required ventilator management (98%) with a median ventilator time of 17 days (range, 3-56 days). Moreover, 24% required extracorporeal membrane oxygenation. While 84% of patients had medical issues at discharge, 68% and 77% had medical issues at ages 1 and 3, respectively. Pulmonary problems were noted in 32% and 47% of the ages 1 and 3 cohorts, respectively. Motor problems were detected in 46% and 71% of the ages 1 and 3 cohorts, respectively. More patients with motor problems at age 1 had abnormal rather than normal postnatal neuroimaging studies (P = .01). Children with motor problems at age 1 were more apt to have an abnormal postnatal neuroimaging finding (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.5-26.8; P = .01), pulmonary problems at age 1 (OR, 4.0; 95% CI, 0.99-16.6; P = .04), and a history of ventilatory management with a linear ventilator time (OR, 1.1; 95% CI, 1.01-1.12; P = .03). CONCLUSIONS Prenatal neuroimaging can accurately image the brain of fetuses with CDH. Abnormal postnatal neuroimaging findings, the presence of pulmonary problems at age 1, and the length of ventilator time were predictors of motor problems at age 1. Ongoing follow-up of CDH survivors should include neurodevelopmental evaluations.

Factors That Impact Resuscitation Preferences for Young People With Severe Developmental Disabilities

A cross-sectional descriptive study was performed to evaluate resuscitation decisions and factors that impact these choices for young people with severe developmental disabilities residing in a skilled nursing facility. Decision-makers were provided with information to clarify resuscitation preferences. Parents/guardians of 30 of the 67 residents also completed a survey. A significant number of decision-makers changed their resuscitation preference to DNR after detailed explanations were provided. Survey results suggest that interpersonal relationships, such as those with family members, religious leader, and physician, were more influential for families who chose full resuscitation compared to those with DNR preferences. Factors such as perception of quality of life and medical condition of the individuals with developmental disabilities were not significantly different between these two groups.

End-of-Life Care Policies and Practices in Pediatric Skilled Nursing Facilities:

Although most children with intellectual and developmental disabilities reside in the community, a subset of children with severe intellectual disability and complex medical needs reside in pediatric skilled nursing facilities. These children have elevated mortality with end-of-life care (EOLC) routinely provided. The present study explored policies and practice in such settings by surveying administrators, nursing directors, and medical directors in facilities across the United States. In addition to EOLC policies and practices, staff reported on their understanding of definitions of do-not-resuscitate orders, family involvement in EOLC planning, and the availability of in-service training. The presence of an official EOLC policy was associated with higher ratings of perception of effectiveness among staff. Staff felt more prepared and comfortable providing EOLC when in-service training was provided.

Child Neurology: Autism as a model Considerations for advanced training in behavioral child neurology

In this article, we advocate for advanced training for child neurologists in behavior and development in order to facilitate the investigation of childhood behavioral and neurodevelopmental disabilities, with autism serving as a model disorder. We explore the current training options and then propose alternative subspecialty training options that focus on behavior and development, with appreciation that most developmental disabilities are not static encephalopathies but, rather, dynamic processes representing the influence of genetics and environment on neural circuitry.

Introduction to the Special Issue on Aging and End of Life

It has been 8 years since the American Journal on Intellectual and Developmental Disabilities (AJIDD) published a landmark two-issue series on the aging (volume 109, numbers 2 and 5). The first issue was edited by Marsha Mailick Seltzer. The confluence of aging with Down syndrome and Alzheimer’s disease was a major catalyst to prompt concern and ignite gerontological interest in this field. Thus, not surprisingly, the preponderance of articles was on topics including risk factors and screening and assessment of dementia in individuals with intellectual disability (ID) with or without Down syndrome. There were also several articles regarding the physical fitness and nutritional status of aging individuals with Down syndrome. The second issue, edited by Tamar Heller, specifically focused on family and service system supports. Prominent themes were caregiver issues, service provision, and service utilization for older adults. The challenges of the increasing population of older adults with intellectual and developmental disability (IDD) require continued description, investigation, advocacy, and intervention. In our call for submissions, we stated, ‘‘There is still a pressing need for further research to delineate physical and mental health concerns associated with aging and the end of life. There is also a great need to study the applicability of aging with IDD in broader contexts.’’ This special issue indeed meets this undertaking by including three empirical research articles regarding (a) prevalence and risk factors associated with falls, (b) chronicity of health conditions compared with the general population, and (c) satisfaction of caregivers with self-directed support models. Three articles review and discuss the present literature with respect to (a) aging individuals with autism spectrum disorders, (b) the transition to retirement and maintenance of meaningful activities on older adulthood, and (c) challenges related to provision of hospice services at the end of life. This issue is more eclectic than the prior published ones pertaining to aging. While each of the articles in this issue poses information on distinct topics, they all are timely and interrelated in their presentation of relevant issues affecting the daily lives of many older adults with IDD. The consequences of sustaining a fall-related injury, along with the complexity of recovery in older adults is a problematic, if not life-threatening, reality to many aging adults with IDD. Knowledge and mitigation of risk factors are key to providing safer settings and avoidance of major injuries. Hsieh, Rimmer, and Heller’s article, ‘‘Prevalence of Falls and Risk Factors in Adults with Intellectual Disability’’ examined data from the Longitudinal Health and Intellectual Disability Study. They report that almost a quarter of the sample had experienced a fall within the last 12 months and that the prevalence increased with increasing age. Risk factors included having arthritis, a seizure disorder, and difficulty lifting/carrying greater than 10 lb; taking more than four medications; using walking aids; and being female. Issues related to health disparities for underrepresented groups, including those with IDD, affect services access and provision as well as health outcomes. Morin, Merineau-Cote, OuelletteKuntz, Tasse, and Kerr’s article, titled ‘‘A Comparison of the Prevalence of Chronic Disease Among People with and Without Intellectual Disability,’’ documents disparity in the rates of certain chronic disease in people with ID compared to the general population. They report that individuals with ID had higher rates of thyroid disorder and heart disease. However, the prevalence of arthritis, migraines, back pain, and food allergies was lower in people with ID compared with the general population. The authors express concern that the lower prevalence might reflect reduced identification and diagnosis of these conditions, because of the need for subjective reports of discomfort for the conditions that were associated with pain. The prevalence of diabetes and asthma did not differ significantly; these conditions have less subjective diagnostic parameters used for assessment and treatment. Family support often comprises a blend of informal and formal caregivers that may change over time. Heller, Arnold, van Heuman, McBride, AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES

Use of Transition Resources by Primary Care Providers for Youth With Intellectual and Developmental Disabilities

Youth with intellectual and developmental disabilities (IDD) often experience difficulties with successful transition from pediatric to adult healthcare. A consultative Transition Clinic for youth with IDD was piloted as a quality improvement project, and assessed the engagement of primary care providers (PCPs) for transition planning after patients were seen in clinic. Although many PCPs found the clinic and resources useful, individual and systemic barriers often prohibited them from participating in transition planning for this patient population. These findings highlight systemic barriers that need to be addressed to ensure successful transition, as well as the need for a specialized Transition Clinic with involvement of specialists with expertise in IDD, such as Developmental-Behavioral Pediatrics, to assist throughout transition process.

End-of-Life Care

With the advent of the modern hospice movement in mid-twentieth century, longer life expectancy reflective of medical advances, growing attention to ethical issues, and development of palliative medicine, increased attention has been paid to palliative and end-of-life care in general. Similarly, interest in issues pertaining to end-of-life care for people with intellectual and developmental disabilities (IDD) also has gained more attention in the professional and lay media. Despite these developments, there continues to be many misconceptions issues specific to people with IDD at end of life. Current medical, social, ethical, and practical issues, as well as challenges faced by children and adults with IDD, reflect the gains that have been made and the ongoing need for further refinement of systems and supports.