CASK pathogenic variant which expands the clinical spectrum for MICPCH syndrome in an adult patient.

The CASK gene and its product protein kinase have been associated with microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome and various other neurodevelopmental disorders. Clinical presentation is highly variable and generally includes intellectual disability, neurological disorders, and dysmorphic features, at a minimum. We present the case of one of the oldest known currently living patients with MICPCH syndrome with additional features not previously described in the literature (midface retrusion, macroglossia, dental crowding, adolescent-onset contractures at large joints, laxity at finger joints, and prominent wrist dystonia). Progressive hypertonicity throughout the patient's life has been managed with serial botulinum toxin injections. A comprehensive multimodal care team including physiatry, physical therapy, exercise therapy, and audiology has been assisting her with hearing deficits, communication skills, and mobility. This potentially expands the phenotype of MICPCH syndrome and provides information about the management of this condition into adulthood.

Spina Bifida Global Learning Collaborative: Educating the next generation of clinicians, researchers, and advocates.

PURPOSE: This project aimed to launch an international learning community to guide the development of a spina bifida (SB) curriculum for global health trainees. METHODS: Using a descriptive study design, a convenience sample of SB curricula were identified in 2022-23 by members of the Spina Bifida World Congress Outreach Committee and evaluated during a series of monthly Zoom calls to discuss SB education in a global health context. Participants included (1) leadership from the ReachAnother Foundation, (2) invited panelists from the Spina Bifida World Congress Global Health Symposium, and (3) global health students and preceptors. Education initiatives in Ethiopia, Sweden, Argentina, Ecuador, and the United States were evaluated vis-à-vis format and content. RESULTS: All of the education initiatives referenced the framework of the World Health Organization International Classification of Functioning, Disability and Health. Formats varied and included both virtual and interactive workshops, print materials, videos, and guides for small group discussion. Content addressed four domains: Folate Prevention, Neurosurgical Training, After Care, and Data Collection. A multidisciplinary approach, partnerships with families, and workforce pipeline training were identified as guiding themes for educating the next generation of SB researchers and clinicians in global health settings. CONCLUSION: The Spina Bifida Global Learning Collaborative is a transnational group of advocates, clinicians, and investigators whose mission is the advancement of SB-related global health education. Lessons learned from the collaborative are being leveraged to develop a global health curriculum for learners, which may improve services for individuals with SB around the globe.

Addressing social determinants of health through customization: Quality improvement, telemedicine, and care coordination to serve immigrant families.

PURPOSE: The purpose of this project was to establish a pathway for electronic medical record (EMR) customization, utilizing quality improvement methodology, to both identify and address adverse social determinants of health (SDOH) among a diverse spina bifida (SB) population. METHODS: Starting in September 2020, the four fundamental steps were to (1) facilitate an advisory committee to safeguard the standard clinical protocols, (2) characterize barriers to implementation, (3) evaluate workflow to sustain data entry capture, and (4) manage the technology platform for seamless integration. The SB clinic was the first clinic within the enterprise to rollout the use of an adverse SDOH mitigation activity. A Spanish-speaking interpreter was scheduled for all clinics, as many families were limited in English proficiency. RESULTS: The customization of the EMR to support an efficient workflow to address SDOH was feasible in a large and diverse urban medical center. Of the 758 patients served in the clinic, a myelomeningocele diagnosis was present in 86% of individuals. While 52% of participants were female, ethnically 52% of individuals served were Latino. Many of these individuals disclosed being recent immigrants to the United States. Often immigration and asylum related issues were at the forefront of the SDOH issues addressed. CONCLUSION: Given the occurrence of adverse SDOH among individuals with SB, many of whom are new Latin-American immigrants, meaningful clinical efforts are needed to both identify and address the causes of the observed disparities. EMR customization is feasible and can identify and, through social prescriptions, address SDOH to support the provision of safe, high quality, and equitable care for vulnerable and medically complex populations at home and potentially abroad.

Weight Status of Children Participating in the National Spina Bifida Patient Registry.

OBJECTIVES: Describe the distribution of weight status categories and determine factors associated with overweight and obesity (OW/OB) in children and adolescents with spina bifida (SB) using the National Spina Bifida Patient Registry. METHODS: Demographic, anthropometric, and clinical data collected from 2009 through 2018 was used to describe the prevalence of OW/OB. The generalized estimating equation model (GEE) identified factors associated with OW/OB among individuals with SB. RESULTS: Participants (n = 7215) were aged 2 to 19 years (mean = 11.1; standard error, 0.06) and 51.4% female. The majority were non-Hispanic white (57.2%) followed by Hispanic or Latino (25.1%) and non-Hispanic Black (7.5%). The myelomeningocele (MMC) subgroup accounted for 76.3%. Most (60.2%) were community ambulators. The overall percentage of OW/OB was 45.2%, with 49.2% of MMC and 32.0% of nonmyelomeningocele OW/OB. Following the Centers for Disease Control Obesity Severity Classification System, 19.7% of MMC were in class 1, 6.6% in class 2, and 3.5% in class 3. Univariate analysis of MMC participants demonstrated demographic (age, sex, race/ethnicity, and clinic region) and clinical variables (functional level of lesion, ambulation, and number of shunt surgeries) were associated with OW/OB. The GEE model showed that OW/OB was independently, and significantly, associated with age, sex, race/ethnicity, lesion levels, and geographic location of the clinics. CONCLUSIONS: The demographic and clinical factors associated with OW/OB in children and adolescents with SB further our understanding of factors contributing to the higher prevalence of OW/OB in this population and may inform OW/OB prevention and treatment strategies.

Spina bifida transition to adult healthcare guidelines.

With an estimated 85% of individuals with spina bifida (SB) surviving into adulthood, SB-specific transition to adult healthcare guidelines are warranted to address the diverse and complex medical, adaptive, and social needs particular to this condition. This commentary discusses the SB Transition Healthcare Guidelines from the 2018 Spina Bifida Association's Fourth Edition of the Guidelines for the Care of People with Spina Bifida, reviews current transition care models in which such guidelines can be implemented, and explores further research topics in SB transition care.

Genetic epidemiology of neural tube defects.

It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the "genomic revolution" has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may be due to the difficulty of assembling large study cohorts for anencephaly or spina bifida. The purpose of this review is to outline the evolution of genetic studies of NTDs, from studies of familial aggregation to candidate gene and genome-wide association studies, through whole-exome and whole-genome sequencing. Strategies for addressing gaps in NTD genetic research are also explored.

Research Needs for Effective Transition in Lifelong Care of Congenital Genitourinary Conditions: A Workshop Sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.

Over the last 5 decades, health-care advances have yielded quantum improvements in the life expectancy of individuals with congenital genitourinary conditions (CGCs), leading to a crisis of care. Many individuals with CGC enter adulthood unprepared to manage their condition. Pediatric CGC specialists lack training to manage adulthood-related health-care issues, whereas adult genitourinary specialists lack training within the context of CGCs. To address these challenges, the National Institutes of Diabetes and Digestive and Kidney Diseases convened individuals with CGCs and experts from a variety of fields to identify research needs to improve transitional urology care. This paper outlines identified research needs.

Life course health and healthcare utilization among adults with spina bifida.

AIM: To evaluate the prevalence of organ system disorders and describe healthcare utilization among adults with spina bifida at a regional clinic. METHOD: This study was a structured chart review using the Rochester Health Status Survey-IV. 65 males, 57 females aged 16 to 59 years were seen at the Spina Bifida Center of Central New York between January 2007 and December 2008 (annual hospitalization rate was 15 out of 100). RESULTS: Hospitalizations and acute outpatient visits were associated with having shunted hydrocephalus, whereas visits to the emergency department were associated with having a decubitus ulcer. Logistic regression models revealed that older adults made proportionately fewer visits to primary care providers than younger adults (odds ratio 0.919; p=0.02). Yet for every 1-year increase in age, the odds of being hospitalized increased by 5% (odds ratio 1.051; p=0.03). INTERPRETATION: Adults with spina bifida have multiple organ-system disorders. They have greater difficulty accessing services, and utilize emergency and inpatient healthcare at higher rates than the general population. In the future, adults with spina bifida will require access to more medical care and preventive services if they are to have optimal health, well-being, and functioning.

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

OBJECTIVE: To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use. SUBJECTS DESIGN: Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland). RESULTS: R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children. CONCLUSION: The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.

Spina bifida grown up.

The majority of people with spina bifida in the United States are now older than 18 years of age. Health care delivery for adults with this condition should include routine surveillance for common conditions such as hypertension, hyperlipidemia and cancer. It should also address spina bifida-related complications such as pressure sores, lymphedema, sexual dysfunction and infertility, and hydrocephalus, as well as chiari-related symptoms such as sleep apnea and urologic and renal functioning. Almost all adults with spina bifida benefit from regular followup with specialists in urology, neurosurgery and physiatry. Health care providers for adults with spina bifida should recognize the impact of executive dysfunction and nonverbal learning disability on self management, independent living, and employment in adults with spina bifida.

Social participation in a nationally representative sample of older youth and young adults with autism.

OBJECTIVE: To describe social participation and identify factors that affect it in a nationally representative sample of adolescents and young adults with autism. METHODS: Longitudinal cohort study using data from the National Longitudinal Transition Study-2. The World Health Organization International Classification of Functioning, Disability, and Health model was used with participation as the dependent category. RESULTS: A nationally representative sample of 725 youth with autism representing a weighted sample of 21,010 individuals was followed up for 4 years. The mean age at first interview was 15.4 years and 19.2 years at follow-up. More than half the youth at follow-up had not gotten together with friends in the previous year and 64% had not talked on the phone with a friend. Being employed or in secondary education was associated with the following factors (odds ratios): problems conversing (0.67), being teased (0.17), mental retardation (0.06), being above the poverty level (4.17), not using prescription medicine (4.11), general health status (2.30), and parental involvement with school (1.69) (all p < .001). CONCLUSIONS: Many adolescents and young adults with autism become increasingly isolated. Although each aspect of social participation had its own distinct pattern of factors related to it, the ability to communicate effectively, less severe autism, coming from an environment that was not impoverished and having parents who advocated were associated with more positive outcomes. These data provide insights into the factors that affect the participation of youth with autism during their transition years and should ultimately lead to interventions that could improve those transitions.

Youth with spina bifida and transitions: health and social participation in a nationally represented sample.

OBJECTIVE: To describe outcomes and identify factors that affect social participation in youth and young adults with spina bifida. STUDY DESIGN: Prospective data from a nationally representative survey of youth and young adults with disabilities were analyzed. The WHO ICF framework was used with participation as the dependent category and (a) body function/structure; (b) activities; (c) personal factors; and (d) environment as independent categories. RESULTS: A nationally representative sample of 130 youth with spina bifida (mean age 15 years) representing 5171 individuals with spina bifida was followed up for 4 years. The general health of the sample declined over the 4-year study period. Although each outcome using the WHO ICF model had its own pattern of factors that related to it, being Latino or not speaking English at home was negatively associated with each of the outcomes. CONCLUSION: The general health of individuals with spina bifida declines during adolescence and early adulthood. Social participation is affected by many factors, and each outcome appears to have its own set of factors that affect it. Future interventions to improve health, well-being, and social participation in adults with spina bifida will need to address factors in all domains.

Obesity across the lifespan among persons with spina bifida.

PURPOSE: Identify risk factors for obesity across the lifespan for individuals with spina bifida. METHODS: Cross sectional chart review study of 203 patients aged 6-58 years. Obesity was based on body mass index. Rates were calculated for children aged 6-11 years; adolescents aged 12-19 years and adults aged > 20 years. Chi-square analyses were used to determine differences in obesity rates among subgroups. An ordered logistic regression model was developed for the three age groups to estimate the probability of a change in BMI classification from normal weight to overweight or overweight to obese, controlling for sex, functional motor level, shunt status and insurance status. RESULTS: Obesity rates for children, adolescents and adults were 18, 8 and 37%, respectively. Obesity rates were higher among adults (chi2 = 27, p < 0.01) and for individuals who were publicly insured (chi2 = 7.2, p < 0.03). The ordered regression model for children demonstrated no independent association between sex, shunt status, functional motor level or insurance status and change in BMI category. For adolescents, lower functional motor level (i.e. sacral) increased the risk of becoming obese (Odds Ratio: 2.13; 95% CI: 1.12-4.06; p < 0.02). Among adults, female sex increased risk (OR = 2.28; 95% CI: 1.03-5.04; p < 0.04). CONCLUSIONS: Obesity rates for children and adolescents with spina bifida are similar to the general population; however, obesity rates are higher among adults, particularly women. Risk factors are similar to those observed in the general population.

Incidence, prevalence, and characteristics of fractures in children, adolescents, and adults with spina bifida.

OBJECTIVE: To determine the age-specific incidence, prevalence, and characteristics of fractures in persons with spina bifida. DESIGN: Year-long historical cross-sectional study. SUBJECTS: Two hundred twenty-one consecutive patients aged 2-58 years evaluated in 2003 at a regional referral center. Twenty percent (n=44) were children age 2-10 years; 30% (n=68) were adolescents age 11-18 years; and 50% (n=109) were adults age 19-58 years. Fifty-five percent (n=121) were female; 64% (n=141) had shunted hydrocephalus. Fifty-eight percent (n=129) were community ambulators. Defect levels included 14% (n=31) thoracic; 37% (n=81) mid-lumbar; 35% (n=79) low-lumbar; and 14% (n = 30) sacral. METHODS: Chart review of 221 consecutive children, adolescents, and adults enrolled in a spina bifida program in Syracuse, New York, was used to determine incidence and prevalence rates. Chi-square was used for subgroup analyses, and linear regression was used to examine independent association of motor level, functional independence (Functional Independence Measures score), body mass index (BMI), shunted hydrocephalus, epilepsy, and/or other congenital anomalies with fractures, controlling for insurance status, race/ethnicity, age, and sex. RESULTS: Annual incidence of fractures among children, adolescents, and adults was 23/1000; 29/1000; and 18/1000, respectively. Overall prevalence was 200/1000. One in 4 patients with fractures reported multiple fractures. Median age at first fracture was 11 years. Most fractures involved the femur or tibia. Comparisons between adult- and childhood-onset fractures were not significant for difference in sex, BMI, defect level, functional independence, shunted hydrocephalus, epilepsy, or other congenital anomalies. In regression models only defect level RR = 1.646 (P = 0.019; 95% CI 1.085-2.498) and age RR = 1.033 (P= 0.036; 95% CI 1.002-1.065) were independently associated with fractures. CONCLUSIONS: Fractures in persons with spina bifida are most common during early adolescence. Environmental modifications may be more effective than pharmacological treatment in reducing the prevalence of fractures in this population.

Improving guideline adherence for the diagnosis of ADHD in an ambulatory pediatric setting.

BACKGROUND: The American Academy of Pediatrics (AAP) has published clinical practice guidelines for the diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). However, implementation of guidelines has been notoriously difficult to achieve in the wider context of changing individual physicians' clinical practice. OBJECTIVE: Implement a formalized diagnostic protocol for ADHD and study whether this protocol improved adherence of pediatric residents and faculty to published guidelines for the diagnosis of ADHD. METHODS: Quasi-experimental retrospective record review of 63 pediatric patients evaluated for ADHD by pediatric residents and faculty in an outpatient pediatric clinic before (n = 25) and after (n = 38) implementation of a formal diagnostic process for ADHD. The key elements of the new diagnostic process include completion of a semistructured interview and mandatory rating scales for home and school. The published AAP guidelines include 1) documentation of Diagnostic and Statistical Manual for Mental Disorders (DSM) IV criteria; 2) evidence of core symptoms obtained directly from home and 3) from school; and 4) assessment for coexisting conditions. Adherence was assessed to each criterion individually (yes/no) and was summarized in a single score. RESULTS: Only 4% of clinicians and nurse practitioners diagnosing children in the before group adhered to all 4 AAP guidelines, compared to 82% in the after group (P < .001). Significant improvement was observed across each of the 4 criteria in the AAP guidelines. Moreover, the improvement in adherence to all 4 guidelines was noted for residents and faculty. CONCLUSION: A significant improvement in adherence to AAP guidelines was obtained for all providers through implementation of a structured diagnostic approach to ADHD.

Mother knows best: medical record management for patients with spina bifida during the transition from pediatric to adult care.

The personal health record has potential to improve health care transition for an emerging population of pediatric patients with complex chronic conditions who survive to adulthood. In this study qualitative techniques were used to assess how young adults with spina bifida and their parents interact with their medical records. Condensation and categorization strategies for inductive research based on Grounded Theory were used to analyze 1) Who is involved in record keeping 2) How the information is stored 3) What information is kept and shared among the different constituencies and 4) When patients and parents need the information. Theme analysis revealed that mothers play a central role in the medical record management of adolescents with spina bifida. The parent-maintained home based records served as a linking pin in a heterogeneous healthcare information environment. These records tended to be organized as time-lines. Parent and patients were concerned about how best to transition their health information management from parent to adult children. Patients and parents uniformly supported the idea of having access to the medical record on-line.

PICUBASICS: an on-line resource for the diagnosis and management of acute illness in children with chronic conditions and disabilities.

Children with disabilities and chronic conditions are more likely than their healthy peers to be admitted to emergency rooms, to be hospitalized, and to require pediatric intensive care. Although many of these admissions are attributable to disease burden, a significant percentage are unscheduled stays for an acute illness that is directly related to a known condition. Such admissions are foreseeable, and therefore may be avoidable. An understanding of typical patterns of events that lead to acute illness in children with chronic conditions might suggest strategies to prevent these illnesses or to minimize the severity of unpreventable illnesses when they occur. When viewed as a marker for avoidable morbidity, an "unanticipated" hospitalization of a child with a chronic condition or disability thus provides an important opportunity for health care quality improvement at the community level.