Developmental profiles of infants with an FMR1 premutation

Abstract Background Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. Methods This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. Results The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. Conclusions These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers

Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis

BACKGROUND: Although considerable progress has been made in the treatment of chronic kidney disease, compromised quality of life continues to be a significant problem for patients receiving hemodialysis (HD). However, in spite of the high prevalence of sleep complaints and disorders in this population, the relationship between these problems and quality of life remains to be well characterized. Thus, we studied a sample of stable HD patients to explore relationships between quality of life and both subjective and objective measures of nocturnal sleep and daytime sleepiness METHODS: The sample included forty-six HD patients, 24 men and 22 women, with a mean age of 51.6 (10.8) years. Subjects underwent one night of polysomnography followed the next morning by a Multiple Sleep Latency Test (MSLT), an objective measure of daytime sleepiness. Subjects also completed: 1) a brief nocturnal sleep questionnaire; 2) the Epworth Sleepiness Scale; and, 3) the Quality of Life Index (QLI, Dialysis Version) which provides an overall QLI score and four subscale scores for Health & Functioning (H&F), Social & Economic (S&E), Psychological & Spiritual (P&S), and Family (F). (The range of scores is 0 to 30 with higher scores indicating better quality of life.) RESULTS: The mean (standard deviation; SD) of the overall QLI was 22.8 (4.0). The mean (SD) of the four subscales were as follows: H&F – 21.1 (4.7); S&E – 22.0 (4.8); P&S – 24.5 (4.4); and, F – 26.8 (3.5). H&F (r(s )= -0.326, p = 0.013) and F (r(s )= -0.248, p = 0.048) subscale scores were negatively correlated with periodic limb movement index but not other polysomnographic measures. The H&F subscale score were positively correlated with nocturnal sleep latency (r(s )= 0.248, p = 0.048) while the H&F (r(s )= 0.278, p = 0.030) and total QLI (r(s )= 0.263, p = 0.038) scores were positively associated with MSLT scores. Both of these latter findings indicate that higher life quality is associated with lower sleepiness levels. ESS scores were unrelated to overall QLI scores or the subscale scores. Subjective reports of difficulty falling asleep and waking up too early were significantly correlated with all four subscale scores and overall QLI. Feeling rested in the morning was positively associated with S&E, P&S, and Total QLI scores. CONCLUSION: Selected measures of both poor nocturnal sleep and increased daytime sleepiness are associated with decreased quality of life in HD patients, underscoring the importance of recognizing and treating these patients' sleep problems

Caregiver opinions about fragile X population screening

To determine caregiver perceptions about population screening for fragile X and examine factors potentially associated with support for screening

Spatial patterns of soil nitrification and nitrate export from forested headwaters in the northeastern United States

Nitrogen export from small forested watersheds is known to be affected by N deposition but with high regional variability. We studied 10 headwater catchments in the northeastern United States across a gradient of N deposition (5.4 - 9.4 kg ha-1 yr-1) to determine if soil nitrification rates could explain differences in stream water NO 3- export. Average annual export of two years (October 2002 through September 2004) varied from 0.1 kg NO3--N ha-1 yr-1 at Cone Pond watershed in New Hampshire to 5.1 kg ha-1 yr-1 at Buck Creek South in the western Adirondack Mountains of New York. Potential net nitrification rates and relative nitrification (fraction of inorganic N as NO3-) were measured in Oa or A soil horizons at 21-130 sampling points throughout each watershed. Stream NO3- export was positively related to nitrification rates (r2 = 0.34, p = 0.04) and the relative nitrification (r2 = 0.37, p = 0.04). These relationships were much improved by restricting consideration to the 6 watersheds with a higher number of rate measurements (59-130) taken in transects parallel to the streams (r 2 of 0.84 and 0.70 for the nitrification rate and relative nitrification, respectively). Potential nitrification rates were also a better predictor of NO3- export when data were limited to either the 6 sampling points closest to the watershed outlet (r2 = 0.75) or sampling points \u3c250 m from the watershed outlet (r2 = 0.68). The basal area of conifer species at the sampling plots was negatively related to NO3- export. These spatial relationships found here suggest a strong influence of near-stream and near-watershed-outlet soils on measured stream NO3- export. Copyright 2012 by the American Geophysical Union

A place for genetic uncertainty: Parents valuing an unknown in the meaning of disease

Klinefelter, Turner, and fragile X syndromes are conditions defined by a genetic or chromosomal variant. The timing of diagnosis, tests employed, specialists involved, symptoms evident, and prognoses available vary considerably within and across these syndromes, but all three share in common a diagnosis verified through a molecular or cytogenetic test. The genetic or chromosomal variant identified designates a syndrome, even when symptoms associated with the particular syndrome are absent. This article analyzes interviews conducted with parents and grandparents of children with these syndromes from across the US to explore how they interpret a confirmed genetic diagnosis that is associated with a range of possible symptoms that may never be exhibited. Parents’ responses indicate that they see the genetic aspects of the syndrome as stable, permanent and authoritative. But they allow, and even embrace, uncertainty about the condition by focusing on variation between diagnosed siblings, the individuality of their diagnosed child, his or her accomplishments, and other positive aspects that go beyond the genetic diagnosis. Some families counter the genetic diagnosis by arguing that in the absence of symptoms, the syndrome does not exist. They use their own expertise to question the perceived certainty of the genetic diagnosis and to employ the diagnosis strategically. These multiple and often conflicting evaluations of the diagnostic label reveal the rich ways families make meaning of the authority attributed to genetic diagnosis

Reading and Phonological Skills in Boys with Fragile X Syndrome

Reading skills are critical for the success of individuals with intellectual disabilities. Literacy has received little attention in fragile X syndrome (FXS), the most common inherited cause of intellectual impairment. This study examined the literacy profile of FXS and tested phonological awareness and autism spectrum disorder (ASD) symptoms as predictors of literacy

Fragile X Newborn Screening: Lessons Learned From a Multisite Screening Study

BACKGROUND: Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. METHODS: Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. RESULTS: A number of publications have resulted from the project. This article summarizes 10 "lessons learned" about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. CONCLUSIONS: The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families