Neonatal progeroid syndrome (NPS), also known as Wiedemann-Rautenstrauch Syndrome, is a rare autosomal recessive disorder characterized by accelerated aging and lipodystrophy from birth. Affected children have extreme intrauterine growth retardation, poor postnatal weight gain, and characteristic facial dysmorphic features such as a triangular shape, pinched nose, pseudohydrocephalus with wide fontanelles and prominent subcutaneous (sc) veins. Generalized loss of sc fat has been reported as a cardinal feature; however, the pattern of fat loss and its association with insulin resistance and its metabolic complications have not been systematically studied. The aim of the current study was to examine body fat distribution and body composition in two girls with NPS using anthropometric measures, whole-body magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DEXA), and to assess metabolic complications such as hyperinsulinemia and dyslipidemia. Both the girls (aged 17 years and 10 years, respectively) had generalized paucity of sc fat on physical examination. However, measurements of skin-fold thickness revealed that sc fat was decreased over the extremities, but preserved over the chest and abdomen. MRI studies confirmed the presence of normal amounts of sc truncal fat, and marked loss of fat from the face and distal extremities. Striking fat loss was also noted in the paravertebral and lateral gluteal regions. Interestingly, body composition analysis with DEXA scan revealed a marked reduction in both the fat and lean tissue mass. Fasting glucose, lipids and insulin levels were not elevated. We conclude that patients with NPS do not have generalized lipodystrophy as previously reported, but fat loss is confined to the face, distal extremities, and possibly the paravertebral and lateral gluteal regions. Metabolic abnormalities related to insulin resistance are also uncommon in this condition.

BACKGROUND: Wiedemann-Rautenstrauch syndrome (WRS) characterizes a neonatal progeroid entity. In the last 30 years, 28 cases have been reported. In most cases of WRS, survival is short and long-term studies are impossible. CASE: In the present report, we describe a patient with WRS followed for 17 years at the Instituto de Genética, Universidad Nacional de Colombia; this is an exceptional survival period for a person with WRS. The information collected through 17 years for the present patient provides new knowledge about the natural evolution of this syndrome. New clinical and laboratory characteristics are compared with those reported for Rautenstrauch's patient "G." CONCLUSIONS: Our results confirm the variability of this syndrome, especially at the neurological level. However, many etiological and pathological aspects of this syndrome remain unknown.

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

We report on a 35-week gestation female fetus with Hutchinson-Gilford progeria (HGP). This patient, who is the first reported with neonatal HGP in the English literature but is the fourth, counting three previous French cases, supports the existence of a more severe prenatal form of progeria. She died 7 hours after birth and presented with intrauterine growth retardation, premature aging, absence of subcutaneous fat, brachydactyly, absent nipples, hypoplastic external genitalia, and abnormal ear lobes. The child's combination of clinical and skeletal manifestations differentiates this form of HGP from other progeroid syndromes with neonatal presentation. We also report previously undescribed autopsy findings including premature loss of hair follicles, premature regression of the renal nephrogenic layer, and premature closure of the growth plates in the distal phalanges that may be related to the aging processes in this condition. We could not find any histological data to support acro-osteolysis, which is the radiographic sign of brachydactyly. The terminal phalanges in HGP seem to be underdeveloped rather than osteolytic.

We report a girl with severe prenatal and postnatal growth retardation, congenital generalized absence of subcutaneous tissue, and facial and somatic changes with some similarities to Wiedemann-Rautenstrauch syndrome (WRS). However, the patient's condition is sufficiently different from those reported previously to suggest that this patient represents a new syndrome. The abnormalities observed in this patient overlap with those of WRS, Cockayne syndrome, type A (CSA), and osteodysplastic primordial dwarfism type III (OPD III), but also include choanal atresia and pigmentary retinopathy.

A boy with features suggesting the diagnosis of Wiedemann-Rautenstrauch syndrome (WRS) or neonatal progeroid syndrome is presented. Abnormal findings included a generalized virtual absence of subcutaneous fat, sparse scalp hair, prominence of veins and muscles, a large and persistent anterior fontanelle and facial dysmorphism (triangular aged face, prominent eyes and scalp veins). Until now, only 13 cases (including one prenatal diagnosis) of this syndrome have been described. Since the borderlines of this syndrome are not very exact, we reviewed the previous reports in order to further delineate this rare syndrome.

Twin brothers and their maternal uncle with a previously undescribed neonatal progeroid syndrome are presented. In addition to progeroid features, they had pseudo-obstruction of the urinary and gastrointestinal tracts, severe leucocytosis, liver dysfunction, and low complex III and IV in muscle but not in liver. Previously described neonatal progeroid syndromes and syndromes featuring pseudo-obstruction are discussed. The two most likely aetiological mechanisms are an X linked single gene disorder or a mitochondrial disorder. The evidence for these possibilities is presented.

A girl with a progeroid appearance, with prominent occiput, blepharophimosis, cataract, arthrogryposis of the upper limbs and severe pulmonary stenosis is described. She died aged less than 6 months. An older sister was born 3 years before with the same appearance and underwent the same fatal evolution. The clinical appearance of this reported patient is compared to the previously published cases with severe neonatal progeroid syndromes.

We report on a 10-year-old Caucasian male with a prematurely aged appearance, delayed bone maturation and dental development, pronounced acro-osteolysis with brachydactyly, and distinctive cutaneous findings including hard, confluent skin lesions with some clinical and histologic resemblance to those of juvenile hyaline fibromatosis (JHF). He also had hyperopia, sensorineural hearing loss, and elevated TSH. Linear growth and intellectual functions were normal. We believe that this patient represents a new progeroid disorder.

OEIS complex (exstrophy of the cloaca) is an association of fetal malformations that includes omphalocele, exstrophy of the bladder, imperforate anus, and spinal defects. Most cases should be prenatally detectable by maternal serum alpha-fetoprotein screening, but an accurate diagnosis is essential for appropriate counselling of the family.

AKT1 controls important processes in medial temporal lobe (MTL) development and plasticity, but the impact of human genetic variation in AKT1 on these processes is not known in healthy or disease states. Here, we report that an AKT1 variant (rs1130233) previously associated with AKT1 protein expression, prefrontal function and schizophrenia, affects human MTL structure and memory function. Further, supporting AKT1's role in transducing hippocampal neuroplasticity and dopaminergic processes, we found epistasis with functional polymorphisms in BDNF and COMT-genes also implicated in MTL biology related to AKT1. Consistent with prior predictions that these biologic processes relate to schizophrenia, we found epistasis between the same AKT1, BDNF and COMT functional variants on schizophrenia risk, and pharmacogenetic interactions of AKT1 with the effects on cognition and brain volume measures by AKT1 activators in common clinical use-lithium and sodium valproate. Our findings suggest that AKT1 affects risk for schizophrenia and accompanying cognitive deficits, at least in part through specific genetic interactions related to brain neuroplasticity and development, and that these AKT1 effects may be pharmacologically modulated in patients.Molecular Psychiatry advance online publication, 26 July 2011; doi:10.1038/mp.2011.91.

Objective:The objective of this study was to describe factors influencing diuretic use by neonatologists caring for very low birth weight neonates.Study Design:We surveyed 400 US neonatologists. Respondents made therapeutic decisions in clinical scenarios involving very low birth weight infants at 7, 14 and 28 days of age.Result:Response rate was 39%. Diuretic therapy was chosen in 31% of scenario decisions, with pro re nata dosing selected early and regular dosing more common at later ages. Diuretic use was strongly associated with method of respiratory support, and was chosen less often by those also choosing fluid restriction and those concerned about patent ductus arteriosus risk. After adjusting for these factors, excessive weight gain, expected improvement in work of breathing and expected decrease in ventilator days were also associated with diuretic use.Conclusion:The extent of and expectations for diuretic therapy by neonatologists caring for very low birth weight neonates may exceed evidence for efficacy.Journal of Perinatology advance online publication, 10 March 2011; doi:10.1038/jp.2011.11.

In recent years, an array of brain mapping techniques has been successfully employed to link individual differences in circuit function or structure in the living human brain with individual variations in the human genome. Several proof-of-principle studies provided converging evidence that brain imaging can establish important links between genes and behaviour. The overarching goal is to use genetically informed brain imaging to pinpoint neurobiological mechanisms that contribute to behavioural intermediate phenotypes or disease states. This special issue on "Linking Genes to Brain Function in Health and Disease" provides an overview over how the "imaging genetics" approach is currently applied in the various fields of systems neuroscience to reveal the genetic underpinnings of complex behaviours and brain diseases. While the rapidly emerging field of imaging genetics holds great promise, the integration of genetic and neuroimaging data also poses major methodological and conceptual challenges. Therefore, this special issue also focuses on how these challenges can be met to fully exploit the synergism of genetically informed brain imaging.

In this article, we investigate the spatial and temporal dynamics of predator and prey populations using an individual-based modeling approach. In our models, the individual is the fundamental unit, and the dynamics are governed by individual rules for growth, movement, reproduction, feeding, and mortality. We first establish the congruence between age-structured predator-prey population models and the corresponding individual-based population model under homogeneous spatial conditions. Given the agreement between the formalisms, we then use the individual-based model to investigate the dynamics of spatially structured predator-prey systems. In particular, we contrast the dynamics of predator-prey systems in which predators adopt either an "ambush" or a "cruising" strategy. We show that the stability of the spatially structured predator-prey system depends on the relative mobility of prey and predators and that prey mobility, in particular, has a strong effect on stability. Local density dependence in prey reproduction can quantitatively alter the asymmetrical influence of prey mobility on stability, but we show that the asymmetry exists when local density dependence is removed. We hypothesize that this asymmetrical response is due to prey "escape" in space caused by differences in rates of spread of prey and predator populations that arise because of fundamental differences between prey and predator reproduction.

All organisms alter their abiotic environment, but ecosystem engineers are species with abiotic effects that may have to be explicitly accounted for when making predictions about population and community dynamics. The goal of this analysis is to identify those conditions in which engineering leads to population dynamics that are qualitatively different than one would predict using models that incorporate only biotic interactions. We present a simple model coupling an ecosystem engineer and the abiotic environment. We assume that the engineer alters environmental conditions at a rate dependent on engineer density and that the environment decays back to original conditions at an exponential rate. We determine when the feedback to population dynamics through environmental state can lead to altered equilibrium densities, bistability, or runaway growth of the engineer population. The conditions leading to changes in dynamics, such as susceptibility of a system to engineering or alteration of density-dependent and density-independent controls, define cases in which the engineering concept is essential for ecological understanding.

Many diseases have both sexual and nonsexual transmission routes, and closely related diseases often differ in their degree of sexual transmission. We investigate the evolution of transmission mode as a function of host social and mating structure using a model in which disease transmission is explicitly dependent on the numbers of sexual and nonsexual contacts (which are themselves a function of population density) and per-contact infection probabilities. Most generally, and in the absence of trade-offs between the degree of sexual transmission and effects on host fecundity and mortality, nonsexual transmission is favored above the social-sexual crossover point (the host density at which the number of nonsexual contacts exceeds the number of sexual contacts), while sexual transmission is favored below this point. When changes in allocation to the two transmission modes are accompanied by changes in mortality or fecundity, both mixed and pure transmission strategies can be favored. If invading genotypes differ substantially from resident genotypes, genetic polymorphism in transmission mode is possible. The evolutionary outcomes are predictable from a knowledge of the equilibrium population sizes in relation to the social-sexual crossover point. Our results also show that predictions about dynamic outcomes, based on rates of invasion for single pathogens into healthy populations, do not adequately describe the resulting disease prevalence nor predict the subsequent evolutionary dynamics; once invasion of a pathogen has occurred, the conditions for spread of a second pathogen are themselves altered. If the host is considered as a single resource, our results show that two pathogens may coexist on a single resource if they use that resource differentially and have differential feedbacks on resource abundance; such resource feedback effects may be present in other biological systems.

Left ventricular assist device (LVAD) implantation has become an established therapy in adults as well as in children as a bridge to heart transplantation or to aid myocardial recovery. We describe the first case worldwide of an infant suffering from Bland-White-Garland syndrome successfully treated with a left ventricular assist device (Berlin Heart(R); Excor(R) Pediatric) as a bridge to heart transplantation for a period of more than one year.

Intrauterine growth retardation (IUGR) is an overlooked problem in full-term infants with birth weights greater than 2,500 g. Birth weight less than the 10th percentile underestimates the presence of IUGR. The purpose of this study was to determine the prevalence of IUGR in full-term infants and to identify sociodemographic and maternal characteristics associated with IUGR. The Ohio Department of Health Vital Statistics database was used to obtain data related to sociodemographic and maternal characteristics. The fetal growth ratio (FGR) was used to determine the presence of IUGR. The sample consisted of 1,569 infants with normal ratios and 1,364 infants classified as IUGR. Infants with IUGR were more often male and African American or Asian American. Maternal characteristics associated with IUGR included history of smoking during pregnancy, lower pre-pregnancy weight, lower weight gain during pregnancy, and inadequate prenatal care. IUGR is present in a significant number of full-term infants with birth weights greater than 2,500 g. The long-term effects of IUGR in these infants remain to be determined.

The authors report the consequence of intra-uterine growth retardation on infancy and adult disease. During infancy in 7 to 10% of cases a growth retardation less than -2 DS, is observed and subsequently needs growth hormone treatment. In adult X syndrome (hypertension, diabetes of 2 types insulino resistant and cardiovascular disease) is observed 18 times more in subjects where the birth weight was low than 2.4 kg. Finally the authors give some recommendations to follow-up of the infants born with a growth restriction.

Here we present a new case of Johanson-Blizzard Syndrome. Clinical features consistent with the diagnosis of Johanson-Blizzard Syndrome in a term neonate are described: intra-uterine growth retardation, aplasia of the nasal alae, midline scalp defect, total situs inversus, imperforate anus, malrotation of the small intestine, pancreatic insufficiency, deafness, and lethal congenital heart defects with dextrocardia. These features were confirmed by findings at autopsy. Parents were consanguineous. We compare these clinical features and findings at autopsy with previous cases reported in the literature.

The syndrome of hemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) is a severe form of preeclampsia and eclampsia. To compare the impact of HELLP syndrome and hypertension in pregnancy (HIP) on neonatal morbidity and mortality, 11 infants born to mothers with HELLP syndrome were recruited between 1993 and 1997 from neonatal records. They were compared to 11 infants born to mothers with HIP and 11 control infants born to healthy mothers matched for gestational age, postnatal age and gender. Cesarean section rate was higher in the HELLP group than in the controls (p < 0.05). HELLP group infants had lower Apgar scores (54.5%< 1 at 5th min), than controls (9.1%)(p < 0.05). Both HELLP and HIP group infants showed a higher incidence of intrauterine growth retardation (63.6% and 54.5%, respectively) than the controls (9.1%)(p < 0.05). The incidence of respiratory distress syndrome (RDS) was similar in HELLP and HIP groups and was greater than that in controls (p = NS). Additionally, the neonatal death rate was the highest in the HELLP group (p = NS).

Clinical and autopsy records of 209 stillborn and 81 miscarried infants with 484 congenital defects of the central nervous system were analysed. Sets of more than one defect were retrospectively classified by pathogenetic criteria as syndrome, sequence, association and midline defects. Pathogenetic thinking makes the prenatal diagnosis of further defects easier if one has already been diagnosed. Statements regarding the most probable localisation of neural tube defects have been made.

This study was designed to evaluate the prevalence of intrauterine growth retardation (IUGR) in Mexican Americans compared to non-Hispanic whites in Arizona. Data were compiled from birth certificates documenting live births in 1986 and 1987. A total of 25,289 Mexican-American and 71,139 white newborns were classified by IUGR. Two methods of IUGR classification were used: the fetal growth ratio (FGR) and the 10th percentile of birthweight by gestational age. A reference growth-distribution data set from the state of California was used to determine IUGR vs non-IUGR newborns. Maternal risk factors were also used to compare IUGR and non-IUGR samples. Overall, Mexican Americans had a lower risk (OR: 0.91) for IUGR than did whites, after controlling for maternal risk factors. Regardless of the IUGR classification method used, more than 88% of IUGR infants were born at term, and more than 60% of IUGR infants had birthweights equal to or greater than 2500 g. Maternal risk factors significantly discriminated between IUGR and non-IUGR infants. Finally, after controlling for maternal risk factors, US-born Mexican mothers were 1.21 times more likely to have an IUGR infant than were Mexico-born mothers. The problem of IUGR and its determinants in Mexican Americans deserves attention in clinical settings.

This study was undertaken to evaluate the relationship between elevated maternal serum alpha fetoprotein (MSAFP) levels and congenital heart defects. Thirty-two infants with isolated major congenital heart defects and whose mothers had had MSAFP screening were identified. In only one case was the MSAFP greater than 2.3 multiples of the median. A review of our experience with women with elevated MSAFP levels did not document a higher rate of congenital heart malformations than would be expected based on estimated frequencies in the general population.

The requirement of greater than one minute of positive pressure ventilation was prospectively used to identify infants suffering from asphyxia at birth in 38,405 consecutive deliveries. Multivariate analysis of high-risk factors associated with increased risk of asphyxia showed the prematurity was the most significant predictor of asphyxia. Asphyxia occurred in 62.3% of infants less than 27 weeks' gestation and decreased to 0.4% in infants greater than 38 weeks' gestation. Presence of asphyxia was associated with significant increase in neonatal mortality of infants greater than 36 weeks' gestation. Of the asphyxiated neonates, growth retardation, hypothermia, hyaline membrane disease, and seizures were significantly associated with an increased risk of death.