Neurodevelopmental profile of siblings with Angelman syndrome due to pathogenic UBE3A variants.

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar. METHODS: Through an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings. RESULTS: Second-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups. CONCLUSIONS: The presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.

Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders.

We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.

Brief report: regression timing and associated features in MECP2 duplication syndrome.

The aim of this study was to determine the frequency, timing, and associated features of developmental regression in MECP2 duplication syndrome. We also examined whether duplication size was associated with regression. Comprehensive psychological evaluations were used to assess 17 boys with MECP2 duplication syndrome. Information about regression was gathered via parent report. Eight of 17 boys exhibited regression in language skills, while seven of 17 exhibited regression in other skill areas. Regression in "other skill" areas coincided with seizure onset and with a prior autism diagnosis in six of seven participants. Regression was not associated with duplication size. Questions remain as to why some boys regress, and future work is necessary to understand the underlying mechanism(s) that causes regression.

Micro-duplications of 1q32.1 associated with neurodevelopmental delay.

Distal partial trisomies involving the region 1q32 have been associated with dysmorphic features and developmental delay [1-11]. To further define the critical region for developmental delay and to investigate the genotype-phenotype association of 1q trisomy syndrome, we report two patients with much smaller (3 Mb and 3.5 Mb in size) trisomic regions on 1q32.1. The two micro-duplications largely overlap and both patients exhibited cognitive and motor delays. Case 1 is a 5-year-old boy with global developmental delay, behavioral problems, pervasive developmental disorder not otherwise specified (PDD-NOS), staring spells, headaches, and paresthesias. Case 2 is a 14-year-old girl with seizures, cognitive and motor difficulties, and minor dysmorphic features. These two cases suggest that 1q32.1 region on distal arm of 1q and genes involved are critical to cognitive and motor development in a gene dosage sensitive manner and that other neurological features are variable within this syndrome.

Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.

BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

Determinants of genital human papillomavirus detection in a US population.

This study investigated the association of selected demographic and behavioral characteristics with the detection of low-risk, high-risk, and uncharacterized genital human papillomavirus (HPV) in women attending clinic for routine nonreferral gynecologic health care. Cervical specimens obtained from 3863 women 18-40 years old (mean, 28 years) with no history of high-grade cervical disease were analyzed for 38 HPV types. Overall, HPV prevalence was 39.2%. The prevalence of high-risk, low-risk, and uncharacterized HPV types was 26.7%, 14.7%, and 13.0%, respectively. As expected, the characteristics most strongly associated with overall HPV detection were age and numbers of lifetime and recent sex partners. Low-risk, high-risk, and uncharacterized HPV detection increased with increasing numbers of sex partners. There was a decline in high-risk and low-risk HPV detection with increasing age but little change in uncharacterized HPV detection. These results suggest that the uncharacterized HPV types have a different natural history than either low-risk or high-risk HPV types.

Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention.

OBJECTIVES: The purpose of this study was to determine the incidence of bleeding, vascular, and ischemic complications using three different heparin regimens after successful intervention. BACKGROUND: The ideal dose and duration of heparin infusion after successful coronary intervention is unknown. METHODS: Patients were randomized to one of three heparin strategies after coronary intervention: Group 1 (n = 157 patients) received prolonged (12 to 24 h) heparin infusion followed by sheath removal; Group 2 (n = 120 patients) underwent early removal of sheaths, followed by reinstitution of heparin infusion for 12 to 18 h; Group 3 (n = 137 patients) did not receive any further heparin after intervention with early sheath removal. The primary end point of the study was the combined incidence of in-hospital bleeding and vascular events. Secondary end points included in-hospital ischemic events, length of stay, cost and one-month outcome. RESULTS: After successful coronary intervention, 414 patients were randomized. Unstable angina or postinfarction angina was present in 83% of patients before intervention. The combined incidence of bleeding and vascular events was 21% in Group 1, 14% in Group 2 and 8% in Group 3 (p = 0.01). The overall incidence of in-hospital ischemic complications was 2.2%; there were no differences between groups. Length of hospital stay was shorter (p = 0.033) and adjusted hospital cost was lower (p < 0.001) for Group 3. At 30 days, the incidence of delayed cardiac and vascular events was similar for all three groups. CONCLUSIONS: Heparin infusion after successful coronary intervention is associated with more minor bleeding and vascular injury, prolonged length of stay and increased cost. In-hospital and one-month ischemic events rarely occur after successful intervention, irrespective of heparin use. Routine postprocedure heparin is not recommended, even in patients who present with unstable ischemic syndromes.

Prevalences of type 2 diabetes, the insulin resistance syndrome, and coronary heart disease in an elderly, biethnic population.

OBJECTIVE: To compare the prevalences of type 2 diabetes, the various cardiovascular risk factors encompassing the insulin resistance syndrome (IRS), and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic whites. RESEARCH DESIGN AND METHODS: Elderly Hispanics (n = 414) and non-Hispanic whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County (Albuquerque, NM; age > or = 65 years), underwent a home interview followed by an interview/examination by a nurse-practitioner, nurse, and nutritionist that included an evaluation of glucose tolerance. Prevalences of total and central obesity, dyslipidemia, hypertension, and microalbuminuria also were determined. History of myocardial infarction, recent angina, and/or coronary bypass graft, and electrocardiograms (ECGs) were used to document CHD. RESULTS: Elderly Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic whites, but the prevalence of impaired glucose tolerance was not increased in Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations, fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics were shorter, weighed less, and had more total body and central obesity. The higher prevalences of dyslipidemia in Hispanics could be explained by a higher prevalence of diabetes. The prevalences of hypertension and CHD were not different for the two ethnic groups. CONCLUSIONS: Elderly Hispanics had twice the prevalence of diabetes and higher prevalences of cardiovascular risk factors associated with IRS. Prevalences of hypertension and CHD were similar in the two ethnic groups.

Prevalence of proteinuria/microalbuminuria in an elderly urban, biethnic community.

INTRODUCTION: The purpose of this study was to compare the prevalences of urinary abnormalities, notably proteinuria and microalbuminuria, in a randomly selected, biethnic population of Hispanic and nonHispanic white males and females and to determine the effects of diabetes, hypertension, and coronary heart disease on these prevalence rates. METHODS: A survey of health and health related issues was conducted on 883 volunteers, mean age 74.1 years, selected randomly from the Medicare rolls of Bernallilo County (Albuquerque), New Mexico. The sample consisted of nearly equal numbers of Hispanic and nonHispanic white males and females. A dipstick urinalysis and test for microalbuminuria was performed on a clean void, untimed urine sample as a part of a 4-hour interview/examination. RESULTS: Of the 696 participants with complete databases, 10.5% had 1+ or greater proteinuria (30 mg/dL or more) by convential urinalysis dipstick and 19.8% had microalbuminuria (50 mg/L or more) by Micral Chemstrip methodology. Participants with diabetes mellitus (Odds Ratio (OR) 2.54, Confidence Interval (CI) 1.71-3.76, p < 0.001), and/or hypertension (OR 2.09, 95% CI 1.46-3.01, p < 0.001) were more likely to have microalbuminuria than participants without either of these conditions. After adjusting for the presence of diabetes and hypertension, there was a trend toward an increased prevalence of coronary heart disease (OR 1.23, 95% CI 0.84-1.81 p = 0.28) in those with microalbuminuria, but this did not reach levels of statistical significance. CONCLUSIONS: Hispanics, even after adjusting for a higher prevalence of diabetes, and for small differences in prevalences of hypertension and coronary heart disease, had more microalbuminuria than nonHispanic whites, and males had more microalbuminuria than females.

Outcome of recruitment and report on participation rate in the New Mexico Elder Health Survey.

The purpose of this paper is to report on the outcome of recruitment and participation rate in the New Mexico Elder Health Survey. This survey is the first community based epidemiological survey to examine health and health related issues of elderly (65 years or older) Hispanics and non-Hispanic whites in Bernalillo County (Albuquerque), New Mexico. This survey was conducted from May 1993 to September 1995. Subjects (N=2200) were randomly selected from the list of 50,700 Medicare recipients residing in Bernalillo County and stratified by ethnicity and gender. Hispanics were identified using a computer program that selects Hispanic surname patterns and ethnicity was verified by self report. Subjects participated in a home interview, followed by an interview and examination in a senior health clinic. Use of the Medicare list resulted in 75.7% (N=1666) of subjects being contacted. Of the 1666 subjects available, 1130 (67.8%) completed a home interview and 883 (54%) completed the full examination. There were no significant differences in participation by ethnicity, but there were significant differences by gender, with women less likely to participate. The mean age of participants was 74 years, age range 65 to 100. Hispanic elderly demonstrated greater economic poverty and lower levels of formal education. Our survey results show that the elderly and Hispanic elderly can be successfully recruited to participate in a research study. This paper is the first to summarize the details of the survey design, present the results of recruitment and participation, and describe the survey participants.

Hypercortisolism, diarrhea with steatorrhea, and massive proteinuria due to pheochromocytoma.

Amelioration or cure of hypertension, hypercortisolism, diarrhea with steatorrhea, and massive proteinuria resulted from excision of a pheochromocytoma that contained immunoreactive ACTH, VIP, and somatostatin. Ectopic ACTH production by the tumor was clearly the cause of the hypercortisolism, and the possible involvement of VIP and somatostatin in the diarrhea and steatorrhea was considered. The response to tumor removal suggested that the mesangioproliferative glomerulonephritis shown on renal biopsy was also a paraneoplastic phenomenon.