Understanding type and quality of relationships between individuals with chromosome 18 syndromes and their siblings.

Siblings of individuals with disabilities hold a pivotal and sometimes unappreciated position in the lives of their brother or sister. We sought to understand the unique challenges and opportunities in relationships between children with chromosome 18 conditions and their siblings and to identify the ways to support this relationship. Participants were recruited through the lay advocacy organization, the Chromosome 18 Registry & Research Society. Fifty-seven siblings from 36 families participated, using an investigator designed instrument, were asked to agree or disagreed with statements from four content areas (information and knowledge about the syndrome, feelings about the sibling relationship, involvement with and caregiving for their sibling, and support and advocacy). Siblings reported that they know their sibling with a disability very well and reported a wide range of emotions regarding their sibling. There was a strong sense of pride in their brother/sister's abilities, and many participants reported attempts to help others understand their brother/sister. Many siblings reported a dislike for the common assumption that their affected sibling is a burden on the family. Most participants reported feeling some degree of responsibility for their affected sibling, but many also reported that they enjoy this role. Sixty-three parents from 36 families responded to the survey. Most parents felt their typically developing children enjoyed teaching new things to their affected child as well as being a good role model for them. Most parents also felt their typically developing child was comfortable telling others about their sibling's condition. Recommendations for interventions and future research are discussed.

Impact of CNS Stimulants for Attention-Deficit/Hyperactivity Disorder on Growth: Epidemiology and Approaches to Management in Children and Adolescents.

Central nervous system stimulants are established treatments for pediatric attention-deficit/hyperactivity disorder with robust efficacy data. Reductions in appetite, weight, and growth velocity are some of the most common concerns regarding the long-term use of central nervous system stimulants in developing children. They are associated with suppression of weight and body mass index in childhood. However, both weight and body mass index often progressively increase over adolescence at rates faster than those seen in non-attention-deficit/hyperactivity disorder youth to the degree that attention-deficit/hyperactivity disorder is associated with elevated body mass index by the end of adolescence regardless of medication use. The capacity of central nervous system stimulants to slow growth was identified 50 years ago. Recent work has established that the growth deficits accumulate during the first 2 years of use and may persist provided medication is used. Early initiation coupled with persistent use through adolescence is most likely to be associated with clinical impactful growth suppression. There has been limited formal investigation of treatments for stimulant-associated reductions in weight and height. The most robust evidence exists for drug holidays improving weight gain. Observational studies suggest that limiting lifetime exposure or discontinuing medication is associated with greater adult height. Additional research is needed to identify the causal mechanisms driving the observed slowing in growth as well as the identification of predictors of clinically impactful growth suppression.

Prevalence and factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes: A report from a tertiary medical center in Central Pennsylvania.

Objective: To explore the rate and factors associated with diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in a single tertiary medical centre in Central Pennsylvania. Methods: Retrospective chart review of all individuals ≤ 18 years of age who were diagnosed with T1D (N = 350) at the Penn State Hershey Pediatric Diabetes Clinic from January 2017 to December 2019. We report logistic regression models for DKA at diagnosis of T1D for age, gender, race/ethnicity, BMI percentile, health insurance, outcome of any healthcare encounter 30 days prior to T1D diagnosis, HbA1c level, altered mental status at diagnosis, and diagnosis of autism spectrum disorder and a multivariable logistic regression model including all aforementioned variables. Results: Of the 350 newly diagnosed children with T1D from 2017 to 2019, 161/350 (46%) presented in DKA. Among patients with DKA, there were 45 (28%) in mild DKA and 116 (72%) in moderate/severe DKA, which represents 13% and 33% of all patients diagnosed with T1D, respectively. Variables associated with increased risk of DKA at presentation of T1D included age (<3 or 9-13), BMI percentile (<3% or > 97%), no referral during preceding healthcare encounter, HbA1c level and altered mental status. In a multivariable model, age (<3 or 9-13), no referral during preceding healthcare encounter, HbA1c level and altered mental status were associated with DKA at presentation, whereas gender, race/ethnicity, BMI percentile, health insurance and autism spectrum disorder diagnosis were not. Discussion: Our study notes an overall higher rate of DKA at diagnosis (46%) compared to the SEARCH study (approximately 30%) but a lower rate compared to a recent study in Colorado children (58%).

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Acanthosis nigricans as a composite marker of cardiometabolic risk and its complex association with obesity and insulin resistance in Mexican American children.

AIM: Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). METHODS: We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. RESULTS: Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI→HOMA-IR→AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. CONCLUSION: Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.

Challenges and Successes in Raising a Child With Type 1 Diabetes and Autism Spectrum Disorder: Mixed Methods Study.

BACKGROUND: Self-management of type 1 diabetes (T1D) requires numerous decisions and actions by people with T1D and their caregivers and poses many daily challenges. For those with T1D and a developmental disorder such as autism spectrum disorder (ASD), more complex challenges arise, though these remain largely unstudied. OBJECTIVE: This study aimed to better understand the barriers and facilitators of raising a child with T1D and ASD. Secondary analysis of web-based content (phase 1) and telephone interviews (phase 2) were conducted to further expand the existing knowledge on the challenges and successes faced by these families. METHODS: Phase 1 involved a qualitative analysis of publicly available online forums and blog posts by caregivers of children with both T1D and ASD. Themes from phase 1 were used to create an interview guide for further in-depth exploration via interviews. In phase 2, caregivers of children with both T1D and ASD were recruited from Penn State Health endocrinology clinics and through the web from social media posts to T1D-focused groups and sites. Interested respondents were directed to a secure web-based eligibility assessment. Information related to T1D and ASD diagnosis, contact information, and demographics were collected. On the basis of survey responses, participants were selected for a follow-up telephone interview and were asked to complete the adaptive behavior assessment system, third edition parent form to assess autism severity and upload a copy of their child's most recent hemoglobin A1c (HbA1c) result. Interviews were transcribed, imported into NVivo qualitative data management software, and analyzed to determine common themes related to barriers and facilitators of raising a child with both ASD and T1D. RESULTS: For phase 1, 398 forum posts and blog posts between 2009 and 2016 were analyzed. Common themes related to a lack of understanding by the separate ASD and T1D caregiver communities, advice on coping techniques, rules and routines, and descriptions of the health care experience. For phase 2, 12 eligible respondents were interviewed. For interviewees, the average age of the child at diagnosis with T1D and ASD was 7.92 years and 5.55 years, respectively. Average self-reported and documented HbA1c levels for children with T1D and ASD were 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol), respectively. Common themes from the interviews related to increased emotional burden, frustration surrounding the amount of information they are expected to learn, and challenges in the school setting. CONCLUSIONS: Caregivers of children with both T1D and ASD face unique challenges, distinct from those faced by caregivers of individuals who have either disorder alone. Understanding these challenges may help health care providers in caring for this unique population. Referral to the diabetes online community may be a potential resource to supplement the care received by the medical community.

Abnormal bone mineral content and density in people with tetrasomy 18p.

Tetrasomy 18p is a rare chromosomal abnormality, resulting from an additional iso-chromosome composed of two copies of the short arm. It is characterized by craniofacial abnormalities, neuromuscular dysfunction, and developmental delay. The Chromosome 18 Clinical Research Center has established the largest cohort of individuals with this rare genetic condition. Here, we describe a case series of 21 individuals with tetrasomy 18p who have a previously unreported clinical finding: low bone mineral density. Most individuals met criteria for low bone density despite being relatively young (mean age of 21 years). Clinicians providing care to individuals affected by Tetrasomy 18p should be aware of their increased risk for decreased bone density and pathological fractures.

Chromosome 18 gene dosage map 2.0.

In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chromosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.

Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: Relationships to glycemic control and other risk factors.

AIMS: We aimed to determine the prevalence of arterial stiffness in young adults with youth-onset type 2 diabetes who previously participated in the TODAY clinical trial and whether arterial stiffness is influenced by their prior diabetes treatment assignment or glycemic control. METHODS: We measured arterial stiffness by femoral, radial, and foot pulse wave velocity (PWV), augmentation index (AIx), and brachial distensibility (BrachD) in 453 TODAY participants (age 20.8 ±â€¯2.5 years, diabetes duration 7.6 ±â€¯1.5 years, 36.4% male, BMI 36.7 ±â€¯8.2 kg/m2) at a mean of 7.6 years post-randomization. Increased arterial stiffness in TODAY youth was defined compared with data from lean controls. We assessed whether glycemic control over time or diabetes treatment in TODAY was associated with arterial stiffness. RESULTS: Arterial stiffness was identified in up to 50% of TODAY participants. Prior diabetes treatment assignment was not associated with higher arterial stiffness. Glycemic control over time was associated with PWV radial and foot only. Age, race-ethnicity, sex, higher blood pressure and BMI were also associated with higher arterial stiffness. CONCLUSIONS: Nearly half of TODAY youth have increased arterial stiffness. Targeting blood pressure and perhaps obesity and glycemic control may positively impact arterial health in adolescents with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.govNCT00081328.

The Chromosome 18 Clinical Resource Center.

BACKGROUND: The Chromosome 18 Clinical Research Center has created a pediatrician-friendly virtual resource center for managing patients with chromosome 18 abnormalities. To date, children with rare chromosome abnormalities have been cared for either symptomatically or palliatively as a reaction to the presenting medical problems. As we enter an era of genomic-informed medicine, we can provide children, even those with individually unique chromosome abnormalities, with proactive medical care and management based on the most contemporary data on their specific genomic change. It is problematic for practicing physicians to obtain and use the emerging data on specific genes because this information is derived from diverse sources (e.g., animal studies, case reports, in vitro explorations) and is often published in sources that are not easily accessible in the clinical setting. METHODS: The Chromosome 18 Clinical Resource Center remedies this challenging problem by curating and synthesizing the data with clinical implications. The data are collected from our database of over 26 years of natural history and medical data from over 650 individuals with chromosome 18 abnormalities. RESULTS: The resulting management guides and video presentations are a first edition of this collated data specifically oriented to guide clinicians toward the optimization of care for each child. CONCLUSION: The chromosome 18 data and guides also serve as models for an approach to the management of any individual with a rare chromosome abnormality of which there are over 1,300 born every year in the US alone.

Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents.

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment-insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood-based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA-IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA-IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.

Randomized Controlled Trial of DHA Supplementation during Pregnancy: Child Adiposity Outcomes.

Investigating safe and effective interventions in pregnancy that lower offspring adiposity is important given the burden of obesity and subsequent metabolic derangements. Our objective was to determine if docosahexaenoic acid (DHA) given during pregnancy to obese mothers results in lower offspring adiposity. This study was a long-term follow-up of a randomized trial of mothers with gestational diabetes or obesity who were randomized to receive DHA supplementation at 800 mg/day or placebo (corn/soy oil) starting at 25-29 weeks gestation. Anthropometric measures were collected at birth and maternal erythrocyte DHA and arachidonic (AA) levels were measured at 26 and 36 weeks gestation. At two- and four-year follow-up time points, offspring adiposity measures along with a diet recall were assessed. A significant increase in erythrocyte DHA levels was observed at 36 weeks gestation in the supplemented group (p < 0.001). While no significant differences by measures of adiposity were noted at birth, two or four years by randomization group, duration of breastfeeding (p < 0.001), and DHA level at 36 weeks (p = 0.002) were associated with body mass index z-score. Our data suggest that DHA supplementation during pregnancy in obese mothers may have long-lasting effects on offspring measures of adiposity.

Genetics of serum carotenoid concentrations and their correlation with obesity-related traits in Mexican American children.

Background: Dietary intake of phytonutrients present in fruits and vegetables, such as carotenoids, is associated with a lower risk of obesity and related traits, but the impact of genetic variation on these associations is poorly understood, especially in children.Objective: We estimated common genetic influences on serum carotenoid concentrations and obesity-related traits in Mexican American (MA) children.Design: Obesity-related data were obtained from 670 nondiabetic MA children, aged 6-17 y. Serum α- and ß-carotenoid concentrations were measured in ∼570 (α-carotene in 565 and ß-carotene in 572) of these children with the use of an ultraperformance liquid chromatography-photodiode array. We determined heritabilities for both carotenoids and examined their genetic relation with 10 obesity-related traits [body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL) cholesterol, triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting insulin and glucose, and homeostasis model assessment of insulin resistance] by using family data and a variance components approach. For these analyses, carotenoid values were inverse normalized, and all traits were adjusted for significant covariate effects of age and sex.Results: Carotenoid concentrations were highly heritable and significant [α-carotene: heritability (h2) = 0.81, P = 6.7 × 10-11; ß-carotene: h2 = 0.90, P = 3.5 × 10-15]. After adjusting for multiple comparisons, we found significant (P ≤ 0.05) negative phenotypic correlations between carotenoid concentrations and the following traits: BMI, WC, FM, and triglycerides (range: α-carotene = -0.19 to -0.12; ß-carotene = -0.24 to -0.13) and positive correlations with HDL cholesterol (α-carotene = 0.17; ß-carotene = 0.24). However, when the phenotypic correlations were partitioned into genetic and environmental correlations, we found marginally significant (P = 0.051) genetic correlations only between ß-carotene and BMI (-0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple comparisons. None of the environmental correlations were significant.Conclusions: The findings from this study suggest that the serum carotenoid concentrations were under strong additive genetic influences based on variance components analyses, and that the common genetic factors may influence ß-carotene and obesity and lipid traits in MA children.

A Pilot Study of Parent Mentors for Early Childhood Obesity.

Objective. To assess the feasibility of a parent mentor model of intervention for early childhood obesity using positive deviance-based methods to inform the intervention. Methods. In this pilot, randomized clinical trial, parent-child dyads (age: 2-5) with children whose body mass index (BMI) was ≥95th percentile were randomized to parent mentor intervention or community health worker comparison. The child's height and weight were measured at baseline, after the six-month intervention, and six months after the intervention. Feasibility outcomes were recruitment, participation, and retention. The primary clinical outcome was BMI z-score change. Results. Sixty participants were enrolled, and forty-eight completed the six-month intervention. At baseline, the BMI z-score in the parent mentor group was 2.63 (SD = 0.65) and in the community health worker group it was 2.61 (SD = 0.89). For change in BMI z-score over time, there was no difference by randomization group at the end of the intervention: -0.02 (95% CI: -0.26, 0.22). At the end of the intervention, the BMI z-score for the parent mentor group was 2.48 (SD = 0.58) and for the community health worker group it was 2.45 (SD = 0.91), both reduced from baseline, p < 0.001. Conclusion. The model of a parent mentor clinical trial is feasible, and both randomized groups experienced small, sustained effects on adiposity in an obese, Hispanic population.

The National Children's Study: An Introduction and Historical Overview.

The National Children's Study (NCS) was an ambitious attempt to map children's health and development in a large representative group of children in the United States. In this introduction, we briefly review the background of the NCS and the history of the multiple strategies that were tested to recruit women and children. Subsequent articles then detail the protocols and outcomes of 4 of the recruitment strategies. It is hoped that lessons learned from these attempts to define a study protocol that could achieve the initial aims of the NCS will inform future efforts to conceptualize and execute strategies to provide generalizable insights on the longitudinal health of our nation's children.

The National Children's Study: Recruitment Outcomes Using the Provider-Based Recruitment Approach.

OBJECTIVE: In 2009, the National Children's Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment. METHODS: The NCS aimed to recruit 18- to 49-year-old women who were pregnant or at risk for becoming pregnant who lived in designated geographic segments within primary sampling units, generally counties. Using provider-based recruitment, 10 study centers engaged providers to enroll eligible participants at their practice. Recruitment models used different levels of provider engagement (full, intermediate, information-only). RESULTS: The percentage of eligible women per county ranged from 1.5% to 57.3%. Across the centers, 3371 potential participants were approached for screening, 3459 (92%) were screened and 1479 were eligible (43%). Of those 1181 (80.0%) gave consent and 1008 (94%) were retained until delivery. Recruited participants were generally representative of the county population. CONCLUSIONS: Provider-based recruitment was successful in recruiting NCS participants. Challenges included time-intensity of engaging the clinical practices, differential willingness of providers to participate, and necessary reliance on providers for participant identification. The vast majority of practices cooperated to some degree. Recruitment from obstetric practices is an effective means of obtaining a representative sample.

Consequences of chromsome18q deletions.

Providing clinically relevant prognoses and treatment information for people with a chromsome18q deletion is particularly challenging because every unrelated person has a unique region of hemizygosity. The hemizygous region can involve almost any region of 18q including between 1 and 101 genes (30 Mb of DNA). Most individuals have terminal deletions, but in our cohort of over 350 individuals 23% have interstitial deletions. Because of this heterogeneity, we take a gene by gene approach to understanding the clinical consequences. There are 196 genes on 18q. We classified 133 of them as dosage insensitive, 15 (8%) as dosage sensitive leading to haploinsufficiency while another 10 (5%) have effects that are conditionally haploinsufficient and are dependent on another factor, genetic or environmental in order to cause an abnormal phenotype. Thirty-seven genes (19%) have insufficient information to classify their dosage effect. Phenotypes attributed to single genes include: congenital heart disease, minor bone morphology changes, central nervous system dysmyelination, expressive speech delay, vesicouretreral reflux, polyposis, Pitt-Hopkins syndrome, intellectual disability, executive function impairment, male infertility, aural atresia, and high frequency sensorineural hearing loss. Additionally, identified critical regions for other phenotypes include: adolescent idiopathic scoliosis and pectus excavatum, Virchow-Robin perivascular spaces, small corpus callosum, strabismus, atopic disorders, mood disorder, IgA deficiency, nystagmus, congenital heart disease, kidney malformation, vertical talus, CNS dysmyelination growth hormone deficiency and cleft palate. Together these findings make it increasingly feasible to compile an individualized syndrome description based on each person's individuated genotype. Future work will focus on understanding molecular mechanisms leading to treatment.

A review of 18p deletions.

Since 18p- was first described in 1963, much progress has been made in our understanding of this classic deletion condition. We have been able to establish a fairly complete picture of the phenotype when the deletion breakpoint occurs at the centromere, and we are working to establish the phenotypic effects when each gene on 18p is hemizygous. Our aim is to provide genotype-specific anticipatory guidance and recommendations to families with an 18p- diagnosis. In addition, establishing the molecular underpinnings of the condition will potentially suggest targets for molecular treatments. Thus, the next step is to establish the precise effects of specific gene deletions. As we look forward to deepening our understanding of 18p-, our focus will continue to be on the establishment of robust genotype-phenotype correlations and the penetrance of these phenotypes. We will continue to follow our 18p- cohort closely as they age to determine the presence or absence of some of these diagnoses, including spinocerebellar ataxia (SCA), facioscapulohumeral muscular dystrophy (FSHD), and dystonia. We will also continue to refine the critical regions for other phenotypes as we enroll additional (hopefully informative) participants into the research study and as the mechanisms of the genes in these regions are elucidated. Mouse models will also be developed to further our understanding of the effects of hemizygosity as well as to serve as models for treatment development.

Tetrasomy 18p: report of cognitive and behavioral characteristics.

Our purpose was to describe intellectual and behavioral characteristics of persons with tetrasomy 18p. This is a more detailed investigation into the cognitive and behavioral characteristics of our previously reported tetrasomy 18p cohort of 43 plus six additional participants. We evaluated the intellectual functioning using standard measures of cognitive ability, measures of executive functioning, adaptive and maladaptive behaviors. Intellectual abilities ranged from mild impairment/borderline normal to severe/profound impairment calling into question the assumption that severe cognitive limitation is always a feature of tetrasomy 18p. For persons with tetrasomy 18p with mild cognitive deficits, the main barriers to successful functioning stems from limited social and metacognitive skill development and behavior regulation problems rather than being solely determined by cognitive deficits alone.

A positive deviance approach to early childhood obesity: cross-sectional characterization of positive outliers.

OBJECTIVE: Positive deviance methodology has been applied in the developing world to address childhood malnutrition and has potential for application to childhood obesity in the United States. We hypothesized that among children at high-risk for obesity, evaluating normal weight children will enable identification of positive outlier behaviors and practices. METHODS: In a community at high-risk for obesity, a cross-sectional mixed-methods analysis was done of normal weight, overweight, and obese children, classified by BMI percentile. Parents were interviewed using a semistructured format in regard to their children's general health, feeding and activity practices, and perceptions of weight. RESULTS: Interviews were conducted in 40 homes in the lower Rio Grande Valley in Texas with a largely Hispanic (87.5%) population. Demographics, including income, education, and food assistance use, did not vary between groups. Nearly all (93.8%) parents of normal weight children perceived their child to be lower than the median weight. Group differences were observed for reported juice and yogurt consumption. Differences in both emotional feeding behaviors and parents' internalization of reasons for healthy habits were identified as different between groups. CONCLUSIONS: We found subtle variations in reported feeding and activity practices by weight status among healthy children in a population at high risk for obesity. The behaviors and attitudes described were consistent with previous literature; however, the local strategies associated with a healthy weight are novel, potentially providing a basis for a specific intervention in this population.