Objective To produce a more reliable, continuous set of occipitofrontal head circumference (OFC) growth reference charts for males and females from birth to adulthood in the United States. Study ...design After investigating the strengths and shortcomings of previous reports, we combined the most recent statistically reliable reports of OFC growth reference data into a locally weighted regression analysis to estimate percentile curves. We used cross-sectional prospective local pediatric data to validate our results. Results We present new age- and sex-appropriate US OFC growth charts from birth to adulthood that include 3rd and 97th percentile cutoff values. Our local pediatric data validate that our new proposed OFC growth charts' assessment of attained OFC growth is comparable with previous references. Conclusions We have eliminated disagreements between multiple current references by unifying previously reported US OFC data into a single set of smoothed male and female growth reference charts from birth to adulthood. This will reduce confusion or errors in interpretation of normal versus abnormal measurements currently encountered by primary care clinicians and subspecialists when using OFC growth charts for the US pediatric population.
Autism spectrum disorders (ASDs) include three main conditions: autistic disorder (AD), pervasive developmental disorder, not otherwise specified (PDD-NOS), and Asperger syndrome. It has been shown ...that many genes associated with ASDs are involved in the neuroligin-neurexin interaction at the glutamate synapse: NLGN3, NLGN4, NRXN1, CNTNAP2, and SHANK3. We screened this last gene in two cohorts of ASD patients (133 patients from US and 88 from Italy). We found 5/221 (2.3%) cases with pathogenic alterations: a 106 kb deletion encompassing the SHANK3 gene, two frameshift mutations leading to premature stop codons, a missense mutation (p.Pro141Ala), and a splicing mutation (c.1820-4 G>A). Additionally, in 17 patients (7.7%) we detected a c.1304+48C>T transition affecting a methylated cytosine in a CpG island. This variant is reported as SNP rs76224556 and was found in both US and Italian controls, but it results significantly more frequent in our cases than in the control cohorts. The variant is also significantly more common among PDD-NOS cases than in AD cases. We also screened this gene in an independent replication cohort of 104 US patients with ASDs, in which we found a missense mutation (p.Ala1468Ser) in 1 patient (0.9%), and in 8 patients (7.7%) we detected the c.1304+48C>T transition. While SHANK3 variants are present in any ASD subtype, the SNP rs76224556 appears to be significantly associated with PDD-NOS cases. This represents the first evidence of a genotype-phenotype correlation in ASDs and highlights the importance of a detailed clinical-neuropsychiatric evaluation for the effective genetic screening of ASD patients.
The clinical features of Phelan-McDermid syndrome (also known as 22q13 deletion syndrome) are highly variable and include hypotonia, speech and other developmental delays, autistic traits and mildly ...dysmorphic features. Patient deletion sizes are also highly variable, prompting this genotype-phenotype association study.
Terminal deletion breakpoints were identified for 71 individuals in a patient cohort using a custom-designed high-resolution oligonucleotide array comparative genomic hybridisation platform with a resolution of 100 bp.
Patient deletion sizes were highly variable, ranging from 0.22 to 9.22 Mb, and no common breakpoint was observed. SHANK3, the major candidate gene for the neurologic features of the syndrome, was deleted in all cases. Sixteen features (neonatal hypotonia, neonatal hyporeflexia, neonatal feeding problems, speech/language delay, delayed age at crawling, delayed age at walking, severity of developmental delay, male genital anomalies, dysplastic toenails, large or fleshy hands, macrocephaly, tall stature, facial asymmetry, full brow, atypical reflexes and dolichocephaly) were found to be significantly associated with larger deletion sizes, suggesting the role of additional genes or regulatory regions proximal to SHANK3. Individuals with autism spectrum disorders (ASDs) were found to have smaller deletion sizes (median deletion size of 3.39 Mb) than those without ASDs (median deletion size 6.03 Mb, p=0.0144). This may reflect the difficulty in diagnosing ASDs in individuals with severe developmental delay.
This genotype-phenotype analysis explains some of the phenotypic variability in the syndrome and identifies new genomic regions with a high likelihood for causing important developmental phenotypes such as speech delay.
Growth curves are essential for determining whether growth parameters lie within normal ranges. In the case of fetal and neonatal autopsy, relevant data are scattered across many publications, and ...few sources examine a large enough sample to be considered definitive. To ameliorate these inadequacies, regressions were created incorporating data from multiple sources both to increase accuracy and to condense available data into a single standard. When measurements were not well studied, the best available published standards are given. These regressions provide a valuable tool for clinicians who need to understand the significance of measurements obtained during autopsy.
Purpose: Determination of epilepsy etiology in population‐based studies is difficult because of the high cost of diagnostic tests. However, cost‐effectiveness may be proven if preventive ...public‐health strategies can be established from the test results. We report an epilepsy population‐based study using clinical and laboratory techniques.
Methods: A medical team administered an epilepsy survey to 88% of the residents by census in the rural county of Salamá, Honduras. Ninety of 100 participants identified with active epilepsy underwent a neurologic examination, video‐electroencephalography (video‐EEG), brain computed tomography (CT) scan, and serum enzyme‐linked immunoelectrotransfer blot (EITB) for cysticercosis. Final diagnoses were based on the International League Against Epilepsy classifications for seizures and epilepsy syndromes. Combined epidemiologic, clinical, video‐EEG, neuroimaging, and serum EITB assays were used for the diagnosis of epilepsy etiologies.
Results: Among 6,473 residents surveyed, 151 persons with epilepsy (prevalence rate, 23.3/1,000) were identified, 100 of whom had active epilepsy (15.4/1,000) on the prevalence day. Incidence was determined to be 92.7/100,000. Partial seizures with or without secondary generalization were common (92.2%). Symptomatic epilepsy (62%) was primarily due to neurocysticercosis (37%), perinatal brain damage (8%), post‐traumatic (3%), and poststroke (2%). Eight percent were idiopathic, and 30% were cryptogenic (unknown cause).
Conclusions: Symptomatic epilepsies primarily explained the high prevalence and incidence of epilepsy in Salamá. Integration of video‐EEG and brain CT scan with clinical‐epidemiologic evaluation was critical for determination of epilepsy etiology. Establishment of specific programs for continuation of epidemiologic surveillance, education, intervention, and long‐term follow‐up will benefit the Salamá region.
Objective To assess the efficacy of folic acid (FA) supplementation and fortification in preventing neural tube defects (NTDs) in a high prevalence region of the United States. Study design Active ...and passive surveillance methods were used to identify all fetuses/infants affected with an NTD in South Carolina. Prevalence rates were compared with FA intake to determine the effects of increased intake on NTD occurrence and recurrence. Results From 1992 to 2009, 916 NTD cases occurred in South Carolina, with isolated defects comprising 79% of cases. The NTD rate decreased 58% during this period. There was one NTD-affected pregnancy in 418 subsequent pregnancies (0.2%) in mothers with earlier NTD-affected pregnancies who consumed periconceptional FA supplements, and there were 4 NTDs in 66 pregnancies (6.1%) in which the mother did not take FA supplements. FA supplementation increased from 8% to 35% from 1992 to 2007, and knowledge of the protective benefits of FA increased from 8% to 65% in women of childbearing age. Conclusions Increased periconceptional intake of FA appeared to reduce NTDs in a high-prevalence region. The rate of spina bifida and anencephaly in South Carolina is now essentially the same (0.69 cases per 1000 live births and fetal deaths) as the 1998 to 2005 US rate (0.69).
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