When the Right (Drug) Should Be Left:Prenatal Drug Exposure and Heterotaxy Syndrome

Background: Recent studies reported an association between prenatal propylthiouracil exposure and birth defects, including abnormal arrangement across the left-right body axis, suggesting an association with heterotaxy syndrome. Methods: This case-control and case-finding study used data from 1981 to 2013 from the EUROCAT birth defect registry in the Northern Netherlands. First, we explored prenatal exposures in heterotaxy syndrome (cases) and Down syndrome (controls). Second, we describe the specific birth defects in offspring of mothers using propylthiouracil (PTU) prenatally. RESULTS: A total of 66 cases with heterotaxy syndrome (incidence 12.1 per 100,000 pregnancies) and 783 controls with Down syndrome (143.3 per 100,000 pregnancies) were studied. No differences in intoxication use during pregnancy were found between cases and controls, including smoking (28.0% vs. 22.7%; p = 0.40), alcohol (14.0% vs. 26.9%; p = 0.052), and recreational drugs (0 vs. 0.3%; p = 1.00). We found an association between heterotaxy syndrome and prenatal drug exposure to follitropin-alfa (5.6% vs. 1.1%; p = 0.04), and drugs used in nicotine dependence (3.7% vs. 0.2%; p = 0.02). Five mothers used PTU during pregnancy and gave birth to a child with trisomy 18, renal abnormalities, or hypospadias and cardiac defects. Conclusion: This study identified follitropin-alfa and drugs used in nicotine dependence as possible teratogens of heterotaxy syndrome. Our data suggest the possibility that there is an increased risk of birth defects (including renal, urological, and cardiac abnormalities) in children born among mothers taking PTU prenatally, but not for heterotaxy syndrome. (C) 2016 Wiley Periodicals, Inc.</p

Detection of G1138A Mutation of the FGFR3 Gene in Tooth Material from a 180-Year-Old Museological Achondroplastic Skeleton

Contains fulltext : 189828.pdf (publisher's version ) (Open Access

Two is a Crowd Two is a Crowd: On the Enigmatic Etiopathogenesis of Conjoined Twinning

In this article, we provide a comprehensive overview of multiple facets in the puzzling genesis of symmetrical conjoined twins. The etiopathogenesis of conjoined twins remains matter for ongoing debate and is currently cited—in virtually every paper on conjoined twins—as partial fission or secondary fusion. Both theories could potentially be extrapolated from embryological adjustments exclusively seen in conjoined twins. Adoption of these, seemingly factual, theoretical proposals has (unconsciously) resulted in crystallized patterns of verbal and graphic representations concerning the enigmatic genesis of conjoined twins. Critical evaluation on their plausibility and solidity remains however largely absent. As it appears, both the fission and fusion theories cannot be applied to the full range of conjunction possibilities and thus remain matter for persistent inconclusiveness. We propose that initial duplication of axially located morphogenetic potent primordia could be the initiating factor in the genesis of ventrally, laterally, and caudally conjoined twins. The mutual position of two primordia results in neo-axial orientation and/or interaction aplasia. Both these embryological adjustments result in conjunction patterns that may seemingly appear as being caused by fission or fusion. However, as we will substantiate, neither fission nor fusion are the cause of most conjoined twinning types; rather what is interpreted as fission or fusion is actually the result of the twinning process itself. Furthermore, we will discuss the currently held views on the origin of conjoined twins and its commonly assumed etiological correlation with monozygotic twinning. Finally, considerations are presented which indicate that the dorsal conjunction group is etiologically and pathogenetically different from other symmetric conjoined twins. This leads us to propose that dorsally united twins could actually be caused by secondary fusion of two initially separate monozygotic twins. An additional reason for the ongoing etiopathogenetic debate on the genesis of conjoined twins is because different types of conjoined twins are classically placed in one overarching receptacle, which has hindered the quest for answers. Clin. Anat. 2019. © 2019 Wiley Periodicals, Inc

Pectus excavatum and carinatum

Pectus excavatum and carinatum are the most common morphological chest wall abnormalities. For both pectus excavatum and carinatum the pathogenesis is largely unknown although various hypotheses exist. Usually, exclusion of an underlying syndromal or connective tissue disorder is the reason for referral for genetic evaluation. A detailed anamnesis and family history are needed as well as a complete dysmorphological physical examination. If no features of an underlying disorder are detected, then the pectus excavatum/carinatum can be considered as an isolated abnormality and no further genetic studies seem indicated. Although cases of non-syndromal pectus excavatum/carinatum with a positive family history fitting Mendelian inheritance have been described, it is possible that these pedigrees represent multifactorial inheritance, as no genetic cause for familial isolated pectus excavatum/carinatum has been described yet. The recurrence risk for a non-familial iolated pectus excavatum/carinatum is unknown, but thought to be low. If other symptoms are found then appropriate further diagnostic studies are indicated as pectus excavatum/carinatum can be part of many syndromes. However, the most important and most frequently observed monogenic syndromes with pectus excavatum/carinatum are Marfan Syndrome and Noonan Syndrom

Dutch teratological collections and their artistic portrayals

Several teratologic collections containing specimens with malformations and syndromes are maintained in a number of Dutch anatomical museums. Technically, these are not works of art or antiquities. However, many have been depicted in illustrations of such high quality that they merit discussion here. We review a selection of specimens and their artistic portrayals which find their origin in four Dutch teratological collections. These museum specimens are more than just intriguing objects for the inquisitive museum visitor. As we will substantiate, these specimens—and their artistic depictions—can be used to find and describe rarely occurring birth defects, provide etiopathogenetic information and are a source of novel diagnosis. Additionally, we briefly discuss the ethical aspects and motivations of exhibiting these specimens, as these collections have to be protected meticulously by the new generation of museum professionals, who eventually determine what kind of past our future will have. It is therefore imperative that these collections of antique specimens are treasured as their importance is easily overlooked

Gunshot trauma in human long bones: towards practical diagnostic guidance for forensic anthropologists

In contrast to cranial gunshot trauma, diagnosis and interpretation of gunshot trauma to long bones remains difficult and controversial. The aim of this study is to review the published literature on fracture patterns resulting from gunshot trauma in human long bones, and to use the described characteristics to provide practical guidance for the forensic anthropologist. In order to achieve this, medical and forensic publications on this topic were reviewed. Several types of fractures, such as linear, oblique, comminuted and butterfly fractures, have been observed in either the shaft or the ends of long bones. Indirect fractures that are not caused by bullets striking bone directly but by bullet-induced forces to the surrounding soft tissue have been found as well. Some of these fractures are related to a specific context or mechanism which might help in the forensic reconstruction of events. It is recommended that future research should focus on available medical data to provide more detailed descriptions on fracture patterns for forensic purposes. Experimentation with bone surrogates and computer modelling might also provide better and more realistic reconstructions of gunshot trauma in the future and provide valuable insights for its diagnosis and interpretation in forensic anthropology

Phenotypically Discordant Anomalies in Conjoined Twins: Quirks of Nature Governed by Molecular Pathways?

A multitude of additional anomalies can be observed in virtually all types of symmetrical conjoined twins. These concomitant defects can be divided into different dysmorphological patterns. Some of these patterns reveal their etiological origin through their topographical location. The so-called shared anomalies are traceable to embryological adjustments and directly linked to the conjoined-twinning mechanism itself, inherently located within the boundaries of the coalescence area. In contrast, discordant patterns are anomalies present in only one of the twin members, intrinsically distant from the area of union. These dysmorphological entities are much more difficult to place in a developmental perspective, as it is presumed that conjoined twins share identical intra-uterine environments and intra-embryonic molecular and genetic footprints. However, their existence testifies that certain developmental fields and their respective developmental pathways take different routes in members of conjoined twins. This observation remains a poorly understood phenomenon. This article describes 69 cases of external discordant patterns within different types of otherwise symmetrical mono-umbilical conjoined twins and places them in a developmental perspective and a molecular framework. Gaining insights into the phenotypes and underlying (biochemical) mechanisms could potentially pave the way and generate novel etiological visions in the formation of conjoined twins itself