Fifty years of recognizable patterns of human malformation: Insights and opportunities.

Now in its 7th edition, Smith's Recognizable Patterns of Human Malformation was first published in 1970. This 1st edition comprised 135 "dysmorphic syndromes of multiple primary defects" and 12 "single syndromic malformations resulting in secondary defects." Of the former, other than a few chromosomal and environmental disorders, most were heritable conditions of then unknown etiology. In 2021, the majority of these conditions are now "solved," a notable exception is Hallermann-Streiff syndrome. The "solved" conditions were typically clinically delineated decades prior to understanding the underlying etiology, which rarely required recent technologies such as exome sequencing (ES) to elucidate. The 7th edition includes nearly 300 syndromes, sequences, and associations. An increasing number of conditions first appearing in the latest editions are sporadic, with many solved using either array CGH or ES. We have reviewed all syndromes that have appeared in "Smith's" with a focus on inheritance, heterogeneity, and year and method of etiologic discovery. Several themes emerge. Genetic heterogeneity and pleiotropy of genes are frequent. Several of the currently "unresolved" syndromes are clinically diverse such as Dubowitz syndrome. Multiple recurrent constellations of embryonic malformations, with VACTERL association as a paradigm, are increasingly likely to have a shared pathogenesis requiring further study.

Oskar Kobylinski (1856-1926) and the first description of Noonan syndrome in the medical literature.

While a student of University in Dorpat (now Tartu, Estonia) Oskar Kobylinski published an article reporting on his 22-year-old patient Leisar Eischikmann, who suffered from a congenital deformity of the neck. Kobylinski described this rare anomaly and called it "flüghautige Verbreitung des Halses" (wing-like extension of the neck). It was only in 1902 when the name pterygium colli was introduced, and it has been in use ever since. This malformation is part of some congenital syndromes, most prominently, Turner syndrome and, more rarely, of Noonan syndrome. As Opitz et al. pointed out, the patient described in the 1883 article from Archiv für Anthropologie is probably the first person with Noonan syndrome to have been pictured in the medical literature. The article was signed only by "O. v. Kobylinski, student of medicine." Further archival research was needed to identify this physician and provide more details about his unusual career.

Limb body wall complex - the history of the entity and presentation of our series of cases.

We present an analysis of two first historically documented limb body wall complex (LBWC) cases and our own contemporary perinatal autopsy series of this rare complex. So far it was supposed that the first case of this complex was reported in 1685 by Paul Portal. Studying the Joachim Oelhaf's autopsy report from 1613 with attached engraving showing the neonate with multiple birth defects led our research team to a conclusion that it was genuinely the first description of LBWC in the medical literature so far. We compared the Oelhaf's case from 1613 and the Portal's autopsy report from 1685 with our series of LBWC cases dissected in the Medical University of Gdansk between 1999 and 2011. Reviewing 1100 autopsy reports performed we encountered 9 cases of this unique complex. The analysis was supported by the literature review.

Multiple abnormalities in the feet and associated changes elsewhere in the skeleton: The case of 3A-7 from a Capsian Site in Algeria.

A skeleton with a number of abnormalities is described involving full discussion of alternative diagnoses. In this complex case, the primary diagnosis is of avulsion of the stem of the bifurcate ligament causing a fracture of the anterior process of the calcaneus. The bilateral fracture identified in Skeleton 3A-7 from Site 12, a Capsian site in Algeria, is a result of the feet being inverted and plantar flexed: the fracture is prone to non-union, which is asymmetrical here. There is also a separate anatomical variation of the feet, 3rd cuneiform and 3rd metatarsal coalition, which was not the cause of trauma. The bifurcate ligament is a major stabilizer of the lateral transverse talar joint, and the trauma could lead to further issues: however, multiple other traumatic changes in 3A-7 most likely occurred at the same time, rather than as the result of pre-existing foot trauma. The asymmetry of the calcaneal condition and asymmetry of the sequelae of the original trauma led to long bone asymmetry, the result of locomotor difficulties.

The prevalence of amnion rupture sequence, limb body wall defects and body wall defects in Alberta 1980-2012 with a review of risk factors and familial cases.

Prevalence rates of amnion rupture sequence, limb body wall defect, and body wall defects vary widely. Comparisons are difficult due to small case numbers and the lack of agreement of definition, classification, and pathogenesis. This study reports the prevalence of cases classified in five distinct categories. The Alberta Congenital Anomalies Surveillance System data on live births, stillbirths, and terminations of pregnancy (<20 weeks gestation) occurring between 1980 through 2012 with the ICD-10 Royal College of Paediatrics and Child Health Adaptation codes used for congenital constriction bands (Q79.80) and body wall complex (Q89.7) were reviewed. During the 33-year-study period, there were 153 eligible cases ascertained from 1,411,652 live births and stillbirths, giving a prevalence of 1.08/10,000 total births. There were more males (52%) than females (45%) and 3% were of unknown sex. The average maternal age, birth weight, and gestation was 27 years, 2,701 g, and 35 weeks, respectively. Limb deficiencies occurred in 78% of cases. Amniotic bands with limb deficiency was the most common phenotype (48%). Digital limb deficiency was the most frequent type (56%); however, cases with body wall defects had more severe types of limb deficiencies. The upper limbs only were affected more times (44%), and there was no side preference. Most cases are sporadic but a number of familial occurrences have been reported although some have insufficient documentation and others misdiagnosed. A review of putative risk factors gives conflicting results. © 2016 Wiley Periodicals, Inc.

Sixteenth-century German woodcut of a male infant with possible disorganization.

History has preserved a beautiful 16th century woodcut print, which depicts an infant with several malformations. The German inscription describes the infant's hypotonia and ectopic growths, and the image itself shows a child with an ectopic accessory third lower limb, a large papilla, and an omphalocele-like growth. The 'case' bears striking similarity to reported human cases of the disorganization (Ds) syndrome. This article describes the woodcut, describes Ds, and then explains how the image may represent the earliest depiction of Ds in history.

Foot polydactyly and bipartite medial cuneiform: A case of co-occurrence in a Celtic skeleton from Verona (Italy).

We report a case of bilateral foot polydactyly and bipartite medial cuneiform in a male individual buried in a Celtic/Roman necropolis (3rd to 1st century BCE) in the city of Verona (Italy). During the construction of an underground garage in the main courtyard of the Bishop's Seminary at Verona between 2005 and 2010, archaeologists uncovered the remains of 174 individuals (108 non-adults and 66 adults). It is thought that these graves could belong to some of the first inhabitants of the urban area of Verona. The individual presented here (US 2807) is a middle-aged male (40-50 years) in a good state of preservation. His estimated stature is 1756 mm (± 32.1 mm). This male presents congenital anomalies in the feet and dental agenesis. We believe this to be the only known archaeological case of bilateral postaxial polydactyly with forked (Y) shape, in which both fifth metatarsals are associated with complete bipartition of the left medial cuneiform and partial bipartition of the right one. Polydactyly is fairly common in modern clinical cases but bipartite medial cuneiform is relatively rare; neither of these congenital conditions is well documented archaeologically.

Microcephalic osteodysplastic primordial dwarfism, with the fascinating history of "Mademoiselle Crachami".

This review critically examines the findings which characterize the dysmorphic, radiologic and behavioral phenotype of Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) and has an historical perspective on it. MOPD is a group of primordial dwarfism syndromes with prenatal onset growth retardation, a typical craniofacial appearance and behavioral phenotype. In 1959, Mann and Russell have described the first case in a detailed report, and named "microcephalic midget of extreme type". In their report; based on historical records and a small painting, they pointed "Mademoiselle Crachami" as the oldest known case.

El destierro de lo maravilloso. Hermafroditas y mutantes sexuales en la España de la Ilustración / The banishment of the marvellous. Hermaphodrites and sexual mutants in enlightenment Spain

Este trabajo presenta una síntesis histórica con objeto de hacer inteligible el desgaste de la creencia colectiva en la existencia de hermafroditas y cambios de sexo, emplazando este proceso en el contexto médico y cultural de la España ilustrada. Analiza en este sentido tres procesos convergentes.En primer lugar, la naturalización del monstruo y el retiro de lo «maravilloso» en la ciencia de la Ilustración. En segundo lugar, el despegue de la Medicina legal moderna y la conversión del facultativo en la autoridad competente relacionada con la identidad sexual. Por último, se describe la tentativa de fundamentar biológicamente las diferencias entre los sexos. El trabajo concluye examinando la proyección de esta herencia intelectual ilustrada en la medicina española de las primeras décadas del siglo XIX (AU)

This article presents a historical synthesis in order to trace how the collective belief in the existence of hermaphrodites and sex-changes was slowly eroded in the changing medical and cultural context of Enlightenment Spain. In order to explain this change, three interlinked processesare outlined. First, the naturalization of the monster and the disappearance of the “marvellous” in Enlightenment science. Second, the consolidation of modern legal or forensic science and the rise of the medical specialist as the relevant authority in the determination of sexual identity. Third, the emergence of the notion of fundamental biological differences between the sexes. The article concludes by discussing the consequences of these shifts for early nineteenth century Spanish medicine (AU)

Hermann Friedberg's case report: an early description of CLOVES syndrome.

CLOVES syndrome is a recently described overgrowth disorder with complex vascular anomalies. Careful analysis of the case report by the German physician Hermann Friedberg "gigantism of the right lower limb" published in 1867 revealed that the report probably represents one of the first written accounts of CLOVES syndrome.

Birth defects before epigenesis.

Physicians have tried to explain the origins of birth defects since antiquity. In early humoralist models, fetal anomalies were most often understood in terms of quantity and quality of male and female seed. Maternal imagination was also considered a key environmental influence on fetal development from Hippocrates, Galen, and into late 17th century preformation.