Partial Syndrome Research Articles

OR38 Unusual HLA a locus resolution for a patient with partial trisomy 6p syndrome

OR38 Unusual HLA a locus resolution for a patient with partial trisomy 6p syndrome

Prenatal identification of partial 3q duplication syndrome

BackgroundThe 3q duplication syndrome is a result of duplication of a large fragment of the long arm of chromosome 3, mainly 3q21-qter, and in most cases it is diagnosed only after birth. The phenotypic consequences resulting from genetic imbalance are an important source of information for genetic counselling, especially in prenatal diagnostics. However, in most cases it is impossible to define them precisely because the final clinical presentation is a result of an overlap, usually due to different sizes of deletions and/or duplications not only chromosome 3 but also of translocation partner chromosome. In this article, we present a prenatal diagnosis of the 3q duplication syndrome in a foetus, arising from a balanced insertion ins (7,3)(q21.2;q12.3q29) carried by the mother.Case presentationThe article presents a case of a 29-year-old woman referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis. The analysis of karyotype using GTG technique and FISH allowed diagnosis of a balanced aberration in the mother, and determined the type of chromosomal rearrangement, which allowed the identification of the origin of the additional genetic material in the foetus and the previous malformed child of the same couple. The use of molecular karyotyping techniques (FISH and aCGH) allowed a precise determination of the size of the imbalanced fragments in the affected siblings.ConclusionsThe aCGH technique is particularly valuable for the diagnostics of submicroscopic deletions and duplications, if no imbalanced chromosomal aberrations are detected by routine cytogenetic tests. It is also a valuable technique for identifying and fully characterizing genetic material of unknown origin, which can’t be identified using routine cytogenetic techniqes. However, it does not allow identification of balanced aberrations in carriers.

Radical-Locator Polynomials and Row-Echelon Partial Syndrome Matrices With Applications to Decoding Cyclic Codes

Partial syndrome matrices and weak-locator polynomials have received considerable attention in recent years due to their applications in decoding cyclic codes. The technical contribution of this paper is threefold: 1) cyclic codes can be decoded by the newly proposed partial syndrome matrices, which generalize the previously known results on the determination of error positions; 2) a new type of polynomial associated with error locations, called radical-locator polynomial , is defined, which includes the weak-locator polynomial as a special case; and 3) a novel class of matrices with many zero entries, called row-echelon partial syndrome matrices , is presented, based on the Newton identities, for efficiently decoding cyclic codes. It is also shown that the radical-locator polynomials can be obtained from the determinants of the above-mentioned (row-echelon) partial syndrome matrices.

Automatic detection of ischemic stroke using higher order spectra features in brain MRI images

The gravity of ischemic stroke is the key factor in deciding upon the optimum therapeutic intervention. Ischemic stroke can be divided into three main groups: lacunar syndrome (LACS), partial anterior circulation syndrome (PACS), and total anterior circulation stroke (TACS), where the corresponding severity is mild, medium, and high, respectively. Herein, a unique method for the automatic detection of ischemic stroke severity is presented. The proposed system is based upon the extraction of higher order bispectrum entropy and its phase features from brain MRI (Magnetic Resonance Imaging) images. For classification, which is used to establish stroke severity, a support vector machine was incorporated into the design. The developed technique effectively detected the stroke lesion, and achieved a sensitivity, specificity, accuracy, and positive predictive value equal to 96.4%, 100%, 97.6% and 100%, respectively. The results were obtained without the need for manual intervention. This design is advantageous over state-of-the-art automated stroke severity detection systems, which require the reading neuroradiologist to manually determine the region of interest. Hence, the method is efficacious for delivering decision support in the diagnosis of ischemic stroke severity, thereby aiding the neuroradiologist in routine screening procedures.

Automated segmentation and classification of brain stroke using expectation-maximization and random forest classifier

Magnetic resonance imaging (MRI) is effectively used for accurate diagnosis of acute ischemic stroke. This paper presents an automated method based on computer aided decision system to detect the ischemic stroke using diffusion-weighted image (DWI) sequence of MR images. The system consists of segmentation and classification of brain stroke into three types according to The Oxfordshire Community Stroke Project (OCSP) scheme. The stroke is mainly classified into partial anterior circulation syndrome (PACS), lacunar syndrome (LACS) and total anterior circulation stroke (TACS). The affected part of the brain due to stroke was segmented using expectation-maximization (EM) algorithm and the segmented region was then processed further with fractional-order Darwinian particle swarm optimization (FODPSO) technique in order to improve the detection accuracy. A total of 192 scan of MRI were considered for the evaluation. Different morphological and statistical features were extracted from the segmented lesions to form a feature set which was then classified with support vector machine (SVM) and random forest (RF) classifiers. The proposed system efficiently detected the stroke lesions with an accuracy of 93.4% using RF classifier, which was better than the results of the SVM classifier. Hence the proposed method can be used in decision-making process in the treatment of ischemic stroke.

MON-LB072 Primary Partial Empty Sella Presenting with Prepubertal Hypogonadotropic Hypogonadism: A Case Report

Objective: This is case report which discusses the approach to diagnosis of a 20 year old male presenting with micropenis and absent secondary sex characteristics. Methods: On physical examination, the patient he has eunuchoid habitus, gynecomastia, and a genital and pubic hair development of Tanner Stage 1. He has a flaccid and stretched penile lengths of 2.5 and 3 centimeters respectively, palpable small, firm left testis and undescended right testis. Neurologic examination was unremarkable except for anosmia. Cranial MRI with contrast are suggestive of partially empty sella. Chromosome analysis was done revealing a karyotype with no numerical and structural aberrations and an XY sex chromosome. He has delayed bone age using Greulich-Pyle method and hormonal tests showed low testosterone, LH, FSH, Estradiol and Beta HCG. Results: The patient has no history of pituitary mass, surgery or radiation. However, his mother used an abortifacient on 5th week of pregnancy. With this history, together with the physical examination and diagnostic results of 46XY chromosome, cranial MRI finding of partial empty sella, delayed bone age, and hormonal tests showing low testosterone, LH, FSH, Estradiol and Beta HCG, the patient was diagnosed with Primary Partial Empty Sella Syndrome (Prepubertal Hypogonadotropic Hypogonadism). Conclusion: The incidence of PES varies depending on means of diagnosis ranging from 5.5-35% in general population. It may display with various endocrine problems. However, prepubertal hypogonadotropic hypogonadism as its main manifestation, presenting as micropenis and lack of secondary sex characteristics is rare since its peak incidence commonly occurs late at 30 to 40 years of age and has a sexual predilection for female with female to male ratio of approximately 5:1. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-037 Diagnosis Challenge in Type 4 Familial Partial Lipodystrophic Syndrome

Introduction: Type 4 familial partial lipodystrophic syndrome (FPLD4) is an autosomal dominant disease due to frameshift variants of PLIN1 gene. This gene encodes perilipin 1, a protein playing a key role in the structure of the adipocyte lipid droplet and in the regulation of lipolysis. Only 6 independent families with FPLD4 have been described. The aim of this work was to identify the major signs of the disease in the largest cohort of FPLD4 patients reported to date. Patients and Methods: Clinical and biological phenotype of 11 new patients with a family history of lipodystrophic syndrome and bearing a frameshift variant of PLIN1 gene, were investigated after written informed consent. Histological examination, and perilipin 1 protein expression analyses by western blot on whole cell extracts were performed on biopsies of adipose tissue in 2 patients. Results: We identified 3 heterozygous frameshift variants of PLIN1, segregating with the disease in 11 patients from 5 independent families. Our team had already described the p.Val398Glyfs*167 variant, and 2 new variants p.Gly362Glyfs*63 and p.Pro403Argfs*164 were identified. In all patients next generation sequencing (NGS) excluded any other molecular defect known to be responsible for lipodystrophy. On the studied adipose tissue samples, the PLIN1 variant leads to an abnormal longer form of perilipin 1 with fat fibrosis. The main signs of FPLD4 associate a partial, but also sometimes generalized lipoatrophy of post-pubertal occurrence and a phenotype of variable severity including muscular hypertrophy, acromegaloid facies, hirsutism, and metabolic complications (hypertriglyceridemia, insulin-resistance, diabetes, liver steatosis). Lipoatrophy might be missing or difficult to identify in men and youth. Leptin level was low or inappropriate to BMI, which was below 30 but not always very low. Conclusion: The clinical phenotype of FPLD4 is quite homogeneous, but the clinical diagnosis requires a careful clinical examination and/or an expert advice. An early genetic diagnosis is recommended to confirm the disease and prevent metabolic complications.

The immature platelet fraction in hypertensive disease during pregnancy.

The aim of our study was to elucidate the role of IPF in preeclampsia, because the immature platelet fraction (IPF) is available in most emergency departments. A number of parameters have been introduced to diagnose preeclampsia/HELLP syndrome. The defined cutoffs of angiogenic and antiangiogenic parameters, soluble fms-like tyrosine kinase 1 and placental growth factor, have been approved for clinical routine. However, these parameters need complex analysis and are expensive. The data of 69 pregnant women between 20 and 42weeks of gestation were analyzed in this retrospective monocentric study. 28 of them had preeclampsia, HELLP syndrome or partial HELLP syndrome fitting the Tennessee criteria (study group 1). Furthermore, 41 normotensive pregnant women were included as controls (study group 2). In both groups the IPF was analyzed. In this study, we demonstrated that the values of IPF were significantly higher in patients with hypertensive diseases than in normotensives, but could not distinguish between preeclampsia and HELLP syndrome. The absolute number of immature platelets of women with preeclampsia was significantly higher and those of HELLP syndrome were significantly lower than values of healthy women. The absolute number of immature platelets as well as mature thrombocytes helps to distinguish between HELLP syndrome and preeclampsia. IPF levels are higher in women with hypertensive pregnancy than in normotensive controls. They could be used to diagnose hypertensive diseases in pregnancy. To distinguish between preeclampsia and HELLP syndrome, thrombocytes or the absolute number of immature platelets is needed.

A Case of Hepatic Rupture Associated with a Right-sided Round Ligament Related to Partial Hellp Syndrome

A Case of Hepatic Rupture Associated with a Right-sided Round Ligament Related to Partial Hellp Syndrome

Hypopituitarism other than sellar and parasellar tumors or traumatic brain injury assessed in a tertiary hospital.

Objective:Data regarding the etiology, clinical and biochemical patterns in hypopituitarism is scant for Pakistan. We describe the characteristics of patients with hypopituitarism other than sellar and parasellar tumors or traumatic brain injury from a tertiary care center in Pakistan.Methods:We conducted a retrospective descriptive study in the Aga Khan University Hospital, Karachi, Pakistan. We studied all patients presenting with hypopituitarism, between January 2004 and December 2013. Clinical, hormonal and imaging data pertinent to the study was collected according to inclusion criteria.Results:Forty-two patients presented to the endocrinology clinics at the Aga Khan University Hospital during the study period. Thirty-seven patients (88.1%) were females. Mean age ± standard deviation of the participants was 53.8 ± 14.7 years. Sixteen patients had secondary infertility and all were females; a majority of patients in this group had Sheehan’s syndrome (n=8) followed by empty sella syndrome (n=3), partial empty sella syndrome (n=2), idiopathic cause (n=2) and tuberculoma (n=1). Eighteen females (48.6%) reported inability to lactate.Conclusions:Non-traumatic hypopituitarism was more common in women, with Sheehan syndrome being the most common cause of hypopituitarism in our study (35.7%). Secondary hypothyroidism was the most common hormonal deficiency. The most commonly reported symptom was weakness.

A rare case of possible vacuolar degeneration of leprosy in brain with segmental necrotizing granulomatous neuritis and horner's syndrome

Leprosy has a predilection for peripheral nerves, but rarely does it involve the central nervous system (CNS). There is a single study of CNS involvement in leprosy showing vacuolar changes of motor neurons in medulla oblongata and spinal cord in autopsy findings. Besides this, there has been only one case report providing direct histopathological and molecular evidence of CNS involvement by leprosy in a living patient. Segmental necrotizing granulomatous neuritis (SNGN) is a rare condition affecting the peripheral nerves in leprosy usually seen as a complication of tuberculoid (TT) and borderline tuberculoid (BT) leprosy. We report the case of a 23-year-old male patient, a case of Hansen's disease (BT) who developed CNS involvement in the form of partial Horner's syndrome (right) and SNGN while on treatment. Magnetic resonance imaging of the brain revealed T2 hyperintense lesion on the dorsal aspect of left pontomedullary junction, suggestive of vacuolar degeneration of leprosy. Histopathology of greater auricular nerve (right) revealed SNGN.

Don't poke the bear: using tracking data to quantify behavioural syndromes in elusive wildlife

Animal personality traits and the emergence of behavioural syndromes, i.e. between-individual correlation of behaviours, are commonly quantified from behavioural observations in controlled environments. Subjecting large and elusive wildlife to controlled test situations is, however, rarely possible, suggesting that ecologists should exploit alternative measures of behaviours for quantifying differences between individuals. Our goal was to test whether movement and space use data can be used to quantify behavioural syndromes in the wild. We quantified six behaviours from GPS and dual motion sensor tracking devices of 46 adult female brown bears followed in southcentral Sweden over the summer and early autumn. As well as daily travel distance, an indicator for activity, and daily displacement, an indicator for exploration, we quantified four behaviours that increase a bear's likelihood of encountering humans and could thus serve as indicators for boldness: diurnality, selection for roads and selection for two open habitat types, bogs and clearcuts, with low lateral cover. We tested (1) whether behaviours showed repeatable between-individual variation (animal personality) and (2) whether behaviours were correlated between individuals and thus formed a behavioural syndrome. Repeatability of behaviours ranged from 0.16 to 0.61 confirming between-individual variation in movement, activity and space use. A multivariate mixed model revealed significant positive correlations between travel distance, displacement and diurnality, suggesting the existence of an activity–exploration and potentially partial boldness syndrome in our bear population. Selection for exposed or human-frequented habitats were uncorrelated with the activity–exploration syndrome and with each other, albeit there was a trend for stronger road avoidance by bears that readily used clearcuts. We show that large tracking data sets can be used to quantify between-individual correlation in spatial behaviours. We suggest that delineating behavioural types from wildlife tracking data will be of increasing interest because of the importance of animal personality for ecological processes, wildlife conservation and human–wildlife coexistence.

Impact of the systematic use of the Gugging Swallowing Screen in patients with acute ischaemic stroke.

Post-stroke dysphagia occurs in up to three quarters of patients with acute stroke and is associated with a higher risk of respiratory infections and poor outcome. Systematic screening of dysphagia in the acute stroke unit is essential to identify patients at risk of aspiration and to provide dietary recommendations. Our study aimed to assess the impact of the systematic application of the Gugging Swallowing Screen (GUSS) in patients with acute ischaemic stroke. This was a retrospective study of consecutive patients with acute ischaemic stroke admitted to an acute stroke unit in two time periods: pre-GUSS (February 2014-July 2015), when the 10-mL water-swallowing test was systematically administered, and GUSS (August 2015-October 2016), when the GUSS test was systematically administered. Groups were compared with regard to baseline and stroke characteristics, and the occurrence of stroke-associated pneumonia (SAP), in-hospital death and 3-month outcome. Of the 344 patients who were included in the study (median age 71years), 51.7% were male with a median National Institutes of Health Stroke Scale score of 11. A total of 204 patients were included during the pre-GUSS period and 140 during the GUSS period. Patients in the GUSS period more frequently had diabetes and partial anterior circulation syndromes, and were more frequently treated with thrombectomy. There was no difference in the occurrence of SAP between the two groups (pre-GUSS, 12.5%; GUSS, 15.1%; P=0.490) and no differences were found concerning in-hospital mortality (P=0.996), 3-month functional independence (P=0.647) or 3-month mortality (P=0.598). The systematic administration of GUSS in a population of patients with acute ischaemic stroke did not reduce the occurrence of SAP, mortality or 3-month functional dependence when compared with the systematic administration of the 10-mL water-swallowing test.

Automated approach for detection of ischemic stroke using Delaunay Triangulation in brain MRI images

It is difficult to develop an accurate algorithm to detect the stroke lesions using magnetic resonance imaging (MRI) images due to variation in different lesion sizes, variation in morphological structure, and similarity in intensity of lesion with normal brain in three types of stroke, namely partial anterior circulation syndrome (PACS), lacunar syndrome (LACS) and total anterior circulation stroke (TACS). In this paper, we have integrated the advantages of Delaunay triangulation (DT) and fractional order Darwinian particle swarm optimization (FODPSO), called DT-FODPSO technique for automatic segmentation of the structure of the stroke lesion. The approach was validated on 192 MRI images obtained from different stroke subjects. Statistical and morphological features were extracted and classified according to the Oxfordshire community stroke project (OCSP) using support vector machine (SVM) and random forest (RF) classifiers. The method effectively detected the stroke lesions and achieved promising results with an average sensitivity of 0.93, accuracy of 0.95, JI of 0.89 and Dice similarity index of 0.93 using RF classifier. These promising results indicates the DT based optimized approach is efficient in detecting ischemic stroke and it can aid the neuro-radiologists to validate their routine screening.

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities

(Abstracted from JAMA 2018;319(5):474–482) Several single-site, active-case ascertainment studies in the United States have shown widely varying prevalence estimates for fetal alcohol spectrum disorders, composed of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder. Prevalence of fetal alcohol spectrum disorders are challenging to estimate using routine surveillance methods, and cases are often misdiagnosed or undiagnosed.

Reliability-Based Windowed Decoding for Spatially Coupled LDPC Codes

In this letter, we propose a reliability-based windowed decoding scheme for spatially coupled (SC) low-density parity-check (LDPC) codes. To mitigate the error propagation along the sliding windowed decoder of the SC LDPC codes, a partial message reservation method is proposed where only the reliable messages generated in the previous decoding window are reserved for the next decoding window. We also propose a partial syndrome check stopping rule for each decoding window, in which only the complete variable nodes are checked. Simulation results show that our proposed scheme significantly improves the error-floor performance compared to the sliding windowed decoder with the conventional weighted bit-flipping algorithm.

P465L-PPARγ mutation confers partial resistance to the hypolipidaemic action of fibrates.

AimsFamilial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPARγ. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated with this mutation using a humanized mouse model that recapitulates most of the clinical symptoms observed in patients who have been phenotyped under different experimental conditions. One of the key clinical manifestations observed, both in humans and mouse models, is the ectopic accumulation of fat in the liver. With this study we aim to dissect the molecular mechanisms that contribute to the excessive accumulation of lipids in the liver and characterize the negative effect of this PPARγ mutation on the activity of PPARα in vivo when activated by fibrates.Material and MethodsP465L‐PPAR mutant and wild‐type mice were divided into 8 experimental groups, 4 different conditions per genotype. Briefly, mice were fed a chow diet or a high‐fat diet (HFD 45% Kcal from fat) for a period of 28 days and treated with WY14643 or vehicle for five days before culling. At the end of the experiment, tissues and plasma were collected. We performed extensive gene expression, fatty acid composition and histological analysis in the livers. The serum collected was used to measure several metabolites and to perform basic lipoprotein profile.ResultsP465L mice showed increased levels of insulin and free fatty acids (FFA) as well as increased liver steatosis. They also exhibit decreased levels of very low density lipoproteins (VLDL) when fed an HFD. We also provide evidence of impaired expression of a number of well‐established PPARα target genes in the P465L mutant livers.ConclusionOur data demonstrate that P465L confers partial resistance to the hypolipidemic action of fibrates. These results show that the fatty liver phenotype observed in P465L mutant mice is not only the consequence of dysfunctional adipose tissue, but also involves defective liver metabolism. All in all, the deleterious effects of P465L‐PPARγ mutation may be magnified by their collateral negative effect on PPARα function.

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities

Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples. To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States. Active case ascertainment methods using a cross-sectional design were used to assess children for fetal alcohol spectrum disorders between 2010 and 2016. Children were systematically assessed in the 4 domains that contribute to the fetal alcohol spectrum disorder continuum: dysmorphic features, physical growth, neurobehavioral development, and prenatal alcohol exposure. The settings were 4 communities in the Rocky Mountain, Midwestern, Southeastern, and Pacific Southwestern regions of the United States. First-grade children and their parents or guardians were enrolled. Alcohol consumption during pregnancy. Prevalence of fetal alcohol spectrum disorders in the 4 communities was the main outcome. Conservative estimates for the prevalence of the disorder and 95% CIs were calculated using the eligible first-grade population as the denominator. Weighted prevalences and 95% CIs were also estimated, accounting for the sampling schemes and using data restricted to children who received a full evaluation. A total of 6639 children were selected for participation from a population of 13 146 first-graders (boys, 51.9%; mean age, 6.7 years [SD, 0.41] and white maternal race, 79.3%). A total of 222 cases of fetal alcohol spectrum disorders were identified. The conservative prevalence estimates for fetal alcohol spectrum disorders ranged from 11.3 (95% CI, 7.8-15.8) to 50.0 (95% CI, 39.9-61.7) per 1000 children. The weighted prevalence estimates for fetal alcohol spectrum disorders ranged from 31.1 (95% CI, 16.1-54.0) to 98.5 (95% CI, 57.5-139.5) per 1000 children. Estimated prevalence of fetal alcohol spectrum disorders among first-graders in 4 US communities ranged from 1.1% to 5.0% using a conservative approach. These findings may represent more accurate US prevalence estimates than previous studies but may not be generalizable to all communities.