Primrose syndrome: Characterization of the phenotype in 42 patients

Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo) submitted versio

Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

Background: Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants. Objective: To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth. Study design: Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity. Results: Examination of the 40 placentas revealed: pathology consistent with maternal vascular under-perfusion (MVU) (n = 24), ascending intrauterine infection (AIUI) (n = 17), villitis of unknown aetiology (VUE) (n = 6), foetal thrombotic vasculopathy (FTV) (n = 6), elevated nucleated red blood cells (NRBCs) (n = 6), and chronic deciduitis (n = 10). SNAKE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10,p = 0.014). The same was found for the presence of FTV (median 30 vs. 10, p = 0.019). No relation existed between SNAPPE and the other placental pathologies. Conclusions: Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Population signals in the middle temporal (MT) area of marmoset visual cortex

In primates, including humans, the perception of motion and the control of eye movements depend on the population activity of neurons in the middle temporal (MT) area of the visual cortex. Much is known about the responses of individual neurons in area MT, but it is unclear how neurons work together to provide motion analysis. In the work of this thesis, I use electrophysiological recordings from area MT of a New World monkey, the common marmoset (Callithrix jacchus), to provide knowledge of the spatial and temporal structure of spiking activity and local field potentials (LFP). I first establish that the functional properties of neurons in area MT of the marmoset are similar to those in the major primate model of visual processing, the macaque monkey. I then use multi-electrode arrays to examine co-variability in spiking activity and LFP during rest, and during presentation of visual stimuli. There are three main findings of this thesis. First, correlated variability is affected by the presentation of a visual stimulus, and its structure depends on whether the visual stimulus is a dot field or a grating. Second, correlated variability has local and global components; the local component is largely independent of the type of visual stimulus used, but the global component depends on whether the stimulus is a dot field or a grating. Third, the distinct structures of spiking co-variability observed during presentations of dot fields and gratings do not reflect distinct local mechanisms, but instead distinct global interactions between local mechanisms that are similarly employed during presentation of a stimulus. Together, these results suggest that visual processing in area MT involves stable neural circuitry that is local, and global neural circuitry that is dynamically modulated by a visual stimulus