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. 32:722–741, 2019.

The most impressive phenotypic appearance of sirenomelia is the presence of a 180°‐rotated, axially positioned, single lower limb. Associated gastrointestinal and genitourinary anomalies are almost always present. This rare anomaly is still the subject of ongoing controversies concerning its nosology, pathogenesis, and possible genetic etiology. Sirenomelia can be part of a syndromic continuum, overlapping with other complex conditions including caudal dysgenesis and VATER/VACTERL/VACTERL‐H associations, which could all be part of a heterogeneous spectrum, and originate from an early defect in blastogenesis. It is imaginable that different “primary field defects,” whether or not genetically based, induce a spectrum of caudal malformations. In the current study, we review the contemporary hypotheses and conceptual approaches regarding the etiology and pathogenesis of sirenomelia, especially in the context of concomitant conditions. To expand on the latter, we included the external and internal dysmorphology of one third trimester sirenomelic fetus from our anatomical museum collection, in which multiple concomitant but discordant anomalies were observed compared with classic sirenomelia, and was diagnosed as VACTERL‐H association with sirenomelia. Birth Defects Research 109:791–804, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

A comprehensive lymphatic system is indispensable for a well‐functioning body; it is integral to the immune system and is also interrelated with the digestive system and fluid homeostasis. The main difficulty in examining the lymphatic system is its fine‐meshed structure. This remains a challenge, leaving patients with uninterpreted symptoms and a dearth of potential therapies. We review the history of the lymphatic system up to the present with the aim of improving current knowledge. Several findings described throughout history have made fundamental contributions to elucidating the lymphatic system. The first contributions were made by the ancient Egyptians and the ancient Greeks. Vesalius obtained new insights by dissecting corpses. Thereafter, Ruysch (1638–1731) gained an understanding of lymphatic flow. In 1784, Mascagni published his illustration of the whole lymphatic network. The introduction of radiological lymphography revolutionized knowledge of the lymphatic system. Pedal lymphangiography was first described by Monteiro (1931) and Kinmonth (1952). Lymphoscintigraphy (nuclear medicine), magnetic resonance imaging, and near‐infrared fluorescence lymphography further improved visualization of the lymphatic system. The innovative dynamic contrast‐enhanced magnetic resonance lymphangiography (DCMRL) transformed understanding of the central lymphatic system, enabling central lymphatic flow disorders in patients to be diagnosed and even allowing for therapeutic planning. From the perspective of the history of lymph visualization, DCMRL has ample potential for identifying specific causes of debilitating symptoms in patients with central lymphatic system abnormalities and even allows for therapeutic planning.

Shared anomalies, always located close to the area of coalescence and observable in virtually every type of conjoined twinning, are currently seen as separate anomalies caused by mostly unknown and seemingly unrelated pathways rather than being connected to the twinning mechanism itself. Therefore, most (case) reports about conjoined twins are mere descriptions of (external) dysmorphologies lacking reflections on the possible origin of their concomitant anomalies. As we will demonstrate in this article, shared anomalies are influenced, and in some cases solely and sequentially explained, by interaction aplasia and neo‐axial orientation; two embryological mechanisms to which each set of conjoined twins is subjected and are responsible for their ultimate phenotypical fate. In this review, we consider how the ventral, lateral and caudal conjunction types and their intermediates determine the phenotypic presentation of the twins, including patterns of shared malformations and anomalies, which in themselves can be indistinguishable from those encountered in singleton cases. Hence, it can be hypothesized that certain anomalies in singletons originate in a fashion similar to that in conjoined twins.

Throughout the last four centuries, many anatomical museums across the world have collected teratological specimens that became precious objects. These can be regarded as spirits of the past which have captured the morphology of diseases through time. These valuable and irreplaceable specimens can be perfectly used in contemporary dysmorphological or genetic research. Unfortunately, due to the historical nature of these specimens and the regularly used aggressive preservation fluids, DNA degradation is often present. Furthermore, the use of material for DNA extraction is restricted to preserve the appearance of these valuable museological specimens. Thus, the most challenging part in this perspective is to harvest sufficient DNA of good quality for further testing without damaging the specimens. Besides fixated specimens, most teratological collections contain dried skeletal and teeth materials which are an excellent source to extract DNA. We here present a DNA-based method that enables genetic identification of the G1138A mutation of the FGFR3 gene in a 180-year-old achondroplastic skeleton, confirming the previously morphologically determined disease. Nuclear DNA was extracted from a premolar tooth and the mutation was found using Sanger sequencing of a small region of the FGFR3 gene.

The anatomical collection of the Anatomical Museum of Leiden University Medical Center (historically referred to as Museum Anatomicum Academiae Lugduno‐Batavae) houses and maintains more than 13,000 unique anatomical, pathological and zoological specimens, and include the oldest teratological specimens of The Netherlands. Throughout four centuries hundreds of teratological specimens were acquired by more than a dozen collectors. Due to the rich history of this vast collection, teratological specimens can be investigated in a unique retrospective sight going back almost four centuries. The entire 19th century collection was described in full detail by Eduard Sandifort (1742–1814) and his son Gerard Sandifort (1779–1848). Efforts were made to re‐describe, re‐diagnose and re‐categorize all present human teratological specimens, and to match them with historical descriptions. In the extant collection a total of 642 human teratological specimens were identified, including exceptional conditions such as faciocranioschisis and conjoined twins discordant for cyclopia, and sirenomelia. Both father and son Sandifort differed in their opinion regarding the causative explanation of congenital anomalies. Whereas, their contemporaries Wouter Van Doeveren (1730–1783) and Andreas Bonn (1738–1817) both presented an interesting view on how congenital anomalies were perceived and explained during the 18th and 19th centuries; the golden age of descriptive teratology. Although this enormous collection is almost 400 years old, it still impresses scientists, (bio)medical students, and laymen visiting and exploring the collections of the Museum Anatomicum in Leiden, The Netherlands.