Delineation of EFTUD2 Haploinsufficiency‐Related Phenotypes Through a Series of 36 Patients

Mandibulofacial dysostosis, Guion‐Almeida type (MFDGA) is a recently delineated multiple congenital anomalies/mental retardation syndrome characterized by the association of mandibulofacial dysostosis (MFD) with external ear malformations, hearing loss, cleft palate, choanal atresia, microcephaly, intellectual disability, oesophageal atresia (OA), congenital heart defects (CHDs), and radial ray defects. MFDGA emerges as a clinically recognizable entity, long underdiagnosed due to highly variable presentations. The main differential diagnoses are CHARGE and Feingold syndromes, oculoauriculovertebral spectrum, and other MFDs. EFTUD2, located on 17q21.31, encodes a component of the major spliceosome and is disease causing in MFDGA, due to heterozygous loss‐of‐function (LoF) mutations. Here, we describe a series of 36 cases of MFDGA, including 24 previously unreported cases, and we review the literature in order to delineate the clinical spectrum ascribed to EFTUD2 LoF. MFD, external ear anomalies, and intellectual deficiency occur at a higher frequency than microcephaly. We characterize the evolution of the facial gestalt at different ages and describe novel renal and cerebral malformations. The most frequent extracranial malformation in this series is OA, followed by CHDs and skeletal abnormalities. MFDGA is probably more frequent than other syndromic MFDs such as Nager or Miller syndromes. Although the wide spectrum of malformations complicates diagnosis, characteristic facial features provide a useful handle.     

Douleur morale,douleur physique : mécanismes neurobiologiques et traitement

Emotional pain endured by depressed patients often resembles to physical pain. Overlaps between pain and suffering are based on several observations and suggest common pathophysiological mechanisms: Neuroimaging studies have highlighted neural networks common to emotional pain and physical pain in healthy subjects; major depressive disorders often occur in patients with chronic pain, and conversely, painful events often occur in depressed patients; antidepressants, including tricyclic antidepressants and serotonin and norepinephrine reuptake inhibitors (SNRIs), are efficient in the treatment of chronic pain, and conversely, certain analgesics are useful in relieving grief. Better understanding of the pathophysiology of emotional pain and its relationship with physical pain could lead to other therapeutic approaches, some of which, such as ketamine, are promising.     

Food images engage subliminal motivation to seek food

Human eating behaviour is motivated and shaped by a complex interaction of internal drives such as hunger, external influences such as environmental cues and the sensory properties of food itself. Thus, as is demonstrated by the example of sensory-specific satiety (SSS), hunger may be reduced but particular foods (for example, desserts) retain their attraction and their ability to prompt consumption. In considering consumption, and overconsumption, it is therefore important to understand the interaction between internal and external drives to eat. Using grip force as a measure of motivation, we examined this interaction using an SSS manipulation. Critically, we sought to determine whether food stimuli would exert their influence even when they were subliminally presented (and thus not accessible to consciousness), and whether this unconscious influence would be flexibly updated in response to changes in food reward value with satiety. Demonstrating that the SSS effect remains when external stimuli are not consciously perceived, our data highlight the importance of even the most subtle, fleeting and even subliminal external events in shaping our motivation towards food.     

Fetal and Infant Growth Patterns and Kidney Function at School Age

Low birth weight is associated with ESRD. To identify specific growth patterns in early life that may be related to kidney function in later life, we examined the associations of longitudinally measured fetal and infant growth with kidney function in school-aged children. This study was embedded in a population-based prospective cohort study among 6482 children followed from fetal life onward. Fetal and childhood growth was measured during second and third trimesters of pregnancy, at birth, and at 6, 12, 24, 36, and 48 months postnatally. At the age of 6 years, we measured kidney volume by ultrasound. GFR was estimated using blood creatinine levels. Higher gestational age-adjusted birth weight was associated with higher combined kidney volume and higher eGFR (per 1 SD score increase in birth weight; 1.27 cm³ [95% confidence interval, 0.61 to 1.93] and 0.78 ml/min per 1.73 m² [95% CI, 0.16 to 1.39], respectively). Fetal weight, birth weight, and weight at 6 months were positively associated with childhood kidney volume, whereas higher second trimester fetal weight was positively associated with higher GFR (all P values<0.05). Fetal and childhood lengths were not consistently associated with kidney function. In this cohort, lower fetal and early infant weight growth is associated with smaller kidney volume in childhood, whereas only lower fetal weight growth is associated with lower kidney function in childhood, independent of childhood growth. Whether these associations lead to an increased risk of kidney disease needs to be studied further.Low birth weight is associated with higher risks of ESRD and hypertension in later life.^1–3 Clearly, low birth weight is not the causal factor per se leading to kidney diseases in later life. Birth weight is the result of various exposures and growth patterns in fetal life and the starting point of childhood growth. It has been hypothesized that especially third trimester fetal growth restriction leads to persistently smaller kidneys with a reduced number of nephrons, which may predispose the individual to kidney disease in adulthood.^4–6 This hypothesis is supported by both animal and human studies, showing that kidney volume and nephron number are reduced in fetal growth-restricted subjects and hypertensive subjects.^7–9 Although nephrogenesis is known to continue until 36 weeks of gestation and cease thereafter, not much is known about the specific critical periods and early growth patterns related to kidney function in later life.¹⁰ Also, whether and to what extent the associations of low birth weight with CKD are explained by preterm birth are not known.¹ Longitudinal studies suggested that the associations of low birth weight with hypertension were stronger in subjects with rapid weight gain in childhood, but results are inconclusive.^11,12 A similar growth pattern has not been identified as a risk factor for kidney diseases yet.Prospective studies linking fetal and early childhood growth patterns to kidney outcomes in later life might help to identify early critical periods for developing impaired kidney function in later life.Therefore, we examined, in a population-based prospective cohort study among 6482 children followed from early fetal life onward (Figure 1), the associations of birth weight, gestational age, birth weight for gestational age, and longitudinally measured fetal and early childhood growth patterns with kidney size and function at school age. We used subclinical variations of kidney function in childhood as outcomes, because they relate to kidney disease in later life.¹³Open in a separate windowFigure 1.Flow chart: exclusion criteria and numbers of participants are given. Total numbers of available outcome measurements are given.