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Two cases of skeletal dysplasia from New Kingdom (c. 1400–1050 BCE) Tombos, Sudan
Abstract
Objective
This project investigates two cases of skeletal dysplasia from archaeological excavations of the New Kingdom Period (c. 1400–1050 BCE) portion of the Tombos cemetery in Sudan. Materials: Fair to well-preserved skeletal remains of two individuals, one adult and one juvenile, are examined here.
Methods
All available skeletal elements were analyzed macroscopically. A differential diagnosis was conducted for each individual.
Results
The adult individual, U36.Sh2.B10, displays bilateral mesomelic dysplasia and Madelung’s deformity. The juvenile individual, U36.Sh2.B5, also displays bilateral mesomelic dysplasia and characteristics associated with Madelung’s deformity.
Conclusions
A differential diagnosis of Léri–Weill dyschondrosteosis (LWD) is suggested for the adult female individual (U36.Sh2.B10). The second case (U36.Sh2.B5) is an approximately three to five-year-old individual and is difficult to diagnose given the young age; however, LWD remains the most likely diagnosis.
Significance
There are few cases of LWD in the paleopathological literature, and fewer still of juveniles. The cases described are useful examples in expanding research demonstrating the variability in the expression of skeletal dysplasias in juveniles and adults.
Limitations
Taphonomic alterations and fragmentation of the crania and portions of the postcrania limited the observation of the full suite of characteristics associated with skeletal dysplasias. U36.Sh2.B5 is difficult to diagnose given the individual’s young age and the possibility that this individual had not yet developed the more observable characteristics associated with these conditions.
Suggestions for further research
Researchers are encouraged to continue examining the range of expression of skeletal dysplasias in juveniles and adults.
... Madelung's deformity (Traversari et al., 2020). The severity of LWD can vary between individuals with more severe forms in females than males (Whitmore & Buzon, 2019). Considering the above, we conclude that LWD is a possible diagnosis for the characteristics observed in Ł3/66/90. ...
The skeletal dysplasias are a group of more than 450 heritable disorders that affect bone and cartilage, along with muscles, tendons and ligaments. Achondroplasia is one of the most common skeletal dysplasias in both current and past populations. It can be transmitted intergenerationally, or it can result from a mutation. This paper aims to describe the lesions visible on the skeleton of a 30‐45 year old male with achondroplasia, who lived during the 9th–11th centuries AD (medieval period) in Łekno, Poland. The Łekno settlement complex (Site 3) includes a cemetery with approximately 400 burials of monks and local lay people. Macroscopic examination facilitated a differential diagnosis that identified a probable case of achondroplastic dwarfism, combined with Léri‐Weill dyschondrosteosis and ulnar hemimelia. This is the first case of dwarfism in the bioarchaeological literature that had been documented and visualised using 3D modellings, which were used to show quantitative differences in articular surface areas between the achondroplastic individual and contemporaries of normal stature. Ulnar hemimelia is most commonly seen today as a component of skeletal dysplasias. The right ulna of this male was significantly shorter than the right radius and the left ulna. It is probable that he had multiple skeletal dysplasia (achondroplasia, Léri‐Weill dyschondrosteosis) as well as ulnar hemimelia as a component of achondroplasia. The combination of these disorders has not been previously reported in the bioarchaeological literature, and this individual is also the first case of achondroplasia and Léri‐Weill dyschondrosteosis from the medieval period in Central Europe. As such, this example is used here to provide insights on a variety of different diseases, syndromes and conditions in Polish medieval populations and which will help in future identification of rare diseases from archaeological sites.
... The data collected for rare diseases, on the other hand, indicate that these conditions are perceived as a specialized and marginal topic, and their evidence is represented by case studies (e.g. Pany and Teschler-Nicola, 2007;Whitmore and Buzon, 2019). However, aggregated by five-year intervals, the data collected for Group A journals indicate an upward trend for both tuberculosis and the four rare diseases together, with the latter showing a higher growth rate. ...
Objective
This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the reasons for this.
Materials
A 45-year bibliometric study of publications in seven bioarchaeological journals, along with two journals and editorial groups of broader scientific focus.
Methods
Analyses of distribution patterns of the search hits and diachronic trends for achondroplasia, autosomal-dominant osteopetrosis, osteogenesis imperfecta, and osteopoikilosis, compared to those for tuberculosis as control measure of coverage.
Results
Studies of ancient rare diseases (ARD) are mostly published as case reports in specialized journals and their number did not benefit from the introduction of biomolecular studies. The higher frequency of cases of achondroplasia suggests that not all rare diseases are equally under-represented.
Conclusions
Rare diseases are still largely under-represented in bioarchaeological literature. Their marginality likely results from a combination of taphonomic, methodological and public visibility factors.
Significance
This article is the first attempt to provide a quantitative assessment of the under-representation of ARD and to outline the factors behind it.
Limitations
Rare diseases are an etiologically heterogeneous group. The number of surveyed journals and articles, as well as targeted diseases might be limiting factors.
Suggestions for Further Research
Increasing collection and dissemination of data on ARD; opening a wide-ranging debate on their definition; implementation of biomolecular studies.
Objective
This paper presents a probable case of Madelung-type deformity of the right lower arm in an individual from the Merovingian burial ground (7th and 8 th century CE) from Gotha-Boilstädt (Germany).
Materials
A female individual with an age-at-death of 40−50 years was investigated.
Methods
Macroscopic, osteometric and radiographic analyses were performed using standard methods.
Results
The individual exhibits an unusual case of dysmelia of the right upper extremity. The shoulder and upper arm displayed gracile muscle attachment marks and less robustness compared to the left side. The ulna was shortened and distorted and the radius was severely deformed.
Conclusions
The results indicate that the individual might have been affected by a unilateral Madelung-type deformity. The severity of this case is greater than that reported in the clinical literature.
Significance
This study places an ancient rare disease into archaeological and paleopathological contexts, allowing for the evaluation of the term “ancient rare disease.” It also highlights the importance of reporting rigorously diagnosed cases in order to raise our level of awareness of the incidence and course of this rare condition in the past.
Limitations
The diagnosis cannot be stated with certainty, and only a handful of possible diagnoses can be offered. Congenital and acquired etiologies must be considered, especially when compared with clinical cases where severity of conditions may be modified by medical intervention.
Suggestions for further research
Genetic analysis might be helpful in the determination of the etiology of the observed Madelung-type deformity.
Skeletons of dwarfs have been found in many archaeological sites from around the world. Nevertheless, their descriptions (morphologically and metrically) are very limited. We describe herein the skeleton of a male dwarf, approximately 35–50 years old, found in the Byzantine cemetery (5th–8th century CE) of Rehovot‐in‐the‐Negev, southern Israel. Living stature was estimated at 120–125 cm. Detailed morphological skeletal descriptions and morphometric analysis, together with computed tomography (CT) observations, suggest a diagnosis of achondroplasia. The long bones anomalies, in tandem with other features such as hydrocephalus and spinal stenosis, are discussed in regard to their effect on the dwarf's daily life. The putative place of dwarfs in early Christian communities, compared with dwarfs from other times and places, will be addressed. Copyright © 2011 John Wiley & Sons, Ltd.
Leri-Weill dyschondrosteosis is a pseudoautosomal dominantly-inherited skeletal dysplasia ascribed to haploinsufficiency of the SHOX gene caused by deletions, point mutations, or partial duplications of the gene, or to heterozygous deletions upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements that show enhancer activity. Recently, two SHOX conserved non-coding element duplications, one upstream and one downstream, were reported in patients referred with idiopathic short stature. To further evaluate the role of these duplications in SHOX-related disorders, we describe seven patients (five with Leri-Weill dyschondrosteosis and two with short stature) all of whom have duplications of part of the upstream or downstream conserved non-coding element regions, identified by multiplex ligation-dependent probe amplification. In addition, we show data from 32 patients with an apparently identical downstream duplication that includes a proposed putative regulatory element (identified by multiplex ligation-dependent probe amplification or array comparative genome hybridization), which results in a variable phenotype from normal to mild Leri-Weill dyschondrosteosis. These additional data provide further evidence that duplications of upstream and downstream long range cis-regulatory DNA elements can result in a SHOX-related phenotype. © 2015 Wiley Periodicals, Inc.
The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies.
Left hand/wrist, forearm and lower leg radiographs were assessed at baseline and after 2 years in children with genetically confirmed SHOX-D (GH-treated and untreated groups) and TS (GH-treated) in a randomised, controlled, multinational study.
Radiological anomalies of hand, wrist and forearm were common in SHOX-D and TS. Radial bowing appeared more prevalent in SHOX-D, while lower leg anomalies were more common in TS. There were no significant differences in radiological findings between GH-treated and untreated patients with SHOX-D after 2 years.
GH treatment had no systematic effect on skeletal findings in SHOX-D, based on limited radiological differences between the GH-treated and untreated groups at 2 years. Bone age radiographs allow assessment of radiological signs indicating a potential diagnosis of SHOX-D and may lead to earlier genetic confirmation and initiation of GH therapy. © 2015 S. Karger AG, Basel.
Short stature is a frequent presenting problem in the pediatric population. Various causes including endocrinopathies, skeletal dysplasias, dysmorphic syndromes and malabsorption have been implicated. In girls with short stature, Turner syndrome is frequently considered in the differential diagnosis and can easily be ruled out with chromosome analysis. However, it is not uncommon for a child to have no identifiable cause of their short stature. ?FOR Advances in the field of genetics have estimated that about 2% of idiopathic short stature is related to haploinsufficiency of the Short stature homeobox (SHOX) gene, which is found on the short arm of the X and Y chromosomes in the pseudoautosomal region. Heterozygous carriers of SHOX mutations may be minimally affected or may present with disproportionate short stature, Madelung deformity and other radiographic findings as in Leri-Weill dyschondrosteosis (LWD). In this article, we report on a 14-year old girl with mesomelic short stature and bilateral Madelung deformities caused by LWD and describe the radiographic findings.
The anomalies observed in the skeleton agree with the most probable diagnosis of achondroplasia, although the missing of more diagnostic districts, such as the skull and spine, precludes a certain diagnosis. Macroscopic examination of the pathological skeleton revealed shortening of the long bones without diaphysis bowing, moderate robustness of the upper limbs with morphological changes of the muscular attachments. The enlargement of the ulnar metaphyseal area probably limited elbow articulation, as reported in achondroplasia. The epiphyses of the lower limbs were not affected by evident alterations. In addition, the irregular shape and osteoarthritic changes in the acetabulum may have been a consequence of pelvic inclination and lumbar lordosis, typical of achondroplasia.
Achondroplasia is currently the most common form of dwarfism (1 case in 10,000) and this was probably the case also in the antiquity, as testified by the figurative arts from ancient Egypt to the Italian Renaissance [18]. In a few cases, the dwarfs were represented as elitarian members, or deities like the Egyptian Bes and Ptah; in most cases, however, they were associated with minor figures often involved in ridiculous scenes, with special capabilities or particular attributes. In Imperial Rome, the presence of dwarfs in the historical sources is related to their role as dancers, music comedians, clowns and jugglers, because the members of the high society developed a pronounced taste for entertainers with evident physical or mental malformations, such as cretins, hunchbacks and dwarfs. The dwarfs were also appreciated as personal attendants, for example the emperors Tiberius, Alexandrus Severus and Marcus Aurelius retained achondroplasic dwarfs as precious counselors.
The Law of the Twelve Tables, drawn up during the Republican Age (V century BC), reported that the pater familias could “expose” the malformed newborns: “IV. 1: A dreadfully deformed child shall be killed.” (Tito Livio, Ab urbe condita libri, III, 31). After five or six centuries, during the Imperial Age, the customs changed and some malformations, such as dwarfism, were appreciated. The dwarfs would certainly arouse interest and curiosity, as testified by some archaeological discoveries like a dwarf-shaped puppet found as funerary equipment in a child’s burial (I-II century AD) from the necropolis of Osteria del Curato in Rome. Despite the possible large presence of dwarfs in the Roman Imperial Age suggested by historical sources, the anthropological records are very poor. At the current state of research none of the over 2200 individuals excavated in the same necropolis of Collatina displayed evidence of this congenital and hereditary disease, excluding a case of proportionate dwarfism.
Towards the end of the Empire, the interest in dwarfs declined and the spread of Christianity contributed to a radical change of social attitude towards them (and the relationship with “freaks” changed in a religious sense). Although the Christian morality imposed assistance and charity towards the weakest, the disease was considered a form of divine punishment, and during the Middle Ages dwarfs, as well as prostitutes, fools, and lepers, were excluded from society. Finally, in the Renaissance the dwarfs returned to receiving consideration as a manifestation of social prestige and started to be an attraction at the Courts, where they were used as advisors and confidants. In modern times the discussion about dwarfism is related to the ethical debate on the identification of malformations during gestation and the consequent possibility to abort.
Leri-Weill Dyschondrosteosis (LWD; OMIM 127300) is a dominantly inherited skeletal dysplasia characterized by disproportionate short stature with predominantly mesomelic limb shortening1. Expression is variable and consistently more severe in females2, who frequently display the Madelung deformity of the forearm (shortening and bowing of the radius with dorsal subluxation of the distal ulna). The rare Langer Mesomelic Dysplasia3 (LD; OMIM 249700), characterized by severe short stature with hypoplasia/aplasia of the ulna and fibula, has been postulated to be the homozygous form of LWD (refs 4−6). In a six-generation pedigree with LWD, we established linkage to the marker DXYS6814 in the pseudoautosomal region (PAR1) of the X and Y chromosomes (Z max = 6.28; =0). Linkage analysis of three smaller pedigrees increased the lod score to 8.68 (=0). We identified submicro-scopic PAR1 deletions encompassing the recently described short stature homeobox-containing gene SHOX (refs 7,8) segregating with the LWD phenotype in 5 families. A point mutation leading to a premature stop in exon 4 of SHOX was identified in one LWD family.
Dyschondrosteosis is a mesomelic form of short stature which occurs in conjunction with a characteristic wrist deformity. Madelung's deformity. A family with dyschondrosteosis had an affected father and two daughters. The affected females had dyschondrosteosis and Madelung's deformity, while the affected males had dyschondrosteosis, but no Madelung's deformity. All affected members had arthralgias. The occurrence of male to male transmission confirms an autosomal dominant inheritance pattern for this disorder.
Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus.
Léri-Weill syndrome (LWS) or dyschondrosteosis represents a short stature syndrome characterised by the mesomelic shortening of the forearms and lower legs and by bilateral Madelung deformity of the wrists. Recently, mutations in the pseudoautosomal homeobox gene SHOX have been shown to be causative for this disorder. This gene has previously been described as the short stature gene implicated in Turner syndrome (TS). We studied 32 Léri-Weill patients from 18 different German and Dutch families and present clinical, radiological and molecular data. Phenotypic inter- and intrafamilial heterogeneity is a frequent finding in LWS, and phenotypic manifestations are generally more severe in females. In males, muscular hypertrophy is a frequent finding. To test for SHOX mutations we used FISH, Southern blot and SSCP analysis as well as long-range PCR and sequencing. We identified (sub)microscopic deletions encompassing the SHOX gene region in 10 out of 18 families investigated. Deletion sizes varied between 100 kb and 9 Mb and did not correlate with the severity of the phenotype. We did not detect SHOX mutations in almost half (41%) the LWS families studied, which suggests different genetic etiologies.
The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skeletal growth in transgenic and knockout mice. The autosomal recessive skeletal dysplasia known as "acromesomelic dysplasia, type Maroteaux" (AMDM) maps to an interval that contains NPR2. We sequenced DNA from 21 families affected by AMDM and found 4 nonsense mutations, 4 frameshift mutations, 2 splice-site mutations, and 11 missense mutations. Molecular modeling was used to examine the putative protein change brought about by each missense mutation. Three missense mutations were tested in a functional assay and were found to have markedly deficient guanylyl cyclase activity. We also found that obligate carriers of NPR2 mutations have heights that are below the mean for matched controls. We conclude that, although NPR-B is expressed in a number of tissues, its major role is in the regulation of skeletal growth.
This study describes a probable proportionate dwarf from a Third Intermediate Period cemetery at Ain Tirghi in the Dakhleh Oasis, Egypt. The skeleton (Burial 22 or B22) is an adult female estimated to be in her mid to late thirties. Most medical literature defines an adult stature of 2 standard deviations below the population mean as an indicator for clinically short stature, with some bioarchaeologists and clinicians identifying severe short stature at 3 standard deviations below the population mean. B22 satisfies either criteria when compared with the Ain Tirghi adult female population mean for measurements of the radii and femora, as well as the summed measurements of the femora and tibiae. Her limb proportions were normal and this, with a lack of morphological abnormalities, eliminated several possible causes of small stature (e.g. achondroplasia). The differential diagnosis for an individual with short stature and normal proportions indicates that she represents a probable case of pituitary dwarfism, or hypopituitarism. B22 was buried in the same fashion as adjacent burials in a family group burial and showed no differential indication of physiological stress or illness. Contextualized with the Egyptological and archaeological evidence of dwarfism in Egypt, this case study considers the social perceptions of dwarfism in ancient Egypt and suggests that pituitary dwarfs, like disproportionate dwarfs, likely led normal, if not privileged lives. Therefore, according to the social theory of disability, B22 was not necessarily disabled despite her impairment.
Studies of interacting/overlapping genetic skeletal disorders are rare for populations today, but even more so for archaeological contexts. The skeletal remains of an adult female (EZ 3-7-1) were excavated in the 1980s from the Middle Woodland (50BC–AD400) context of the Elizabeth site (11PK512) in the lower Illinois Valley (LIV), USA. Reported here are the standard score (z-score) comparisons of the measured skeletal differences of EZ 3-7-1 with a reference sample and a re-analysis of the individual’s pathological changes, with special consideration placed on refining the disease diagnosis. The impressive preservation and meticulous recovery of these skeletal remains have provided the opportunity to identify the first and earliest archaeological example of an individual (EZ 3-7-1) with a combined genetic skeletal dysplasia, Leri-Weill dyschondrosteosis and achondroplasia.
Madelung deformity is a complex entity that is not completely understood. It is a rare condition caused by asymmetric growth at the distal radial physis secondary to partial ulnar-sided arrest. A shortened radius that curves palmarly and ulnarly, a dorsally prominent ulnar head, and a triangular arrangement of the carpal bones characterize the deformity. It occurs more commonly in females than males and typically affects both wrists. The deformity may occur in isolation or as a part of a genetic syndrome. Due to varied inheritance patterns, a clear family history may be lacking. Few studies exist on the natural history of the disease, as well as long-term data on those who have had surgical intervention. Nonoperative management is recommended for asymptomatic individuals. Pain, stiffness, and aesthetic concerns have been cited as indications for surgical intervention. Vicker ligament release, physiolysis, radial osteotomies, and/or ulnar shortening procedures may effectively correct radiologic alignment and provide improvement in wrist appearance and pain.
Bioarchaeology is more than “just” the study of the biological aspects of archaeology. It is more than “just” paleopathology, although this is frequently how the wider community views osteoarchaeology or bioarchaeology (Perry 2007). Bioarchaeology is the study of people who lived in the past, carried out using archaeology, but with a framework situated within, and developed from, biological methods. The key word is “people” as it is the people, or more specifically the individuals themselves, who are too often forgotten, or “lost”, in the broader whole.
Identification of Pathological Conditions in Human Skeletal Remains provides an integrated and comprehensive treatment of pathological conditions that affect the human skeleton. There is much that ancient skeletal remains can reveal to the modern orthopaedist, pathologist, forensic anthropologist, and radiologist about the skeletal manifestations of diseases that are rarely encountered in modern medical practice. Beautifully illustrated with over 1,100 photographs and drawings, this book provides essential text and materials on bone pathology, which will improve the diagnostic ability of those interested in human dry bone pathology. It also provides time depth to our understanding of the effect of disease on past human populations.
Madelung deformity of the wrist is more common in females and is often associated with Leri Weill dyschondrosteosis, a mesomelic form of dwarfism. Patients with Madelung deformity often report wrist deformity resulting from the prominence of the relatively long ulna. The typical Madelung deformity is associated with a Vickers ligament that creates a tether across the volar-ulnar radial physis that restricts growth across this segment. The distal radius deforms in the coronal (increasing radial inclination) and the sagittal (increasing volar tilt) planes. There is lunate subsidence and the proximal carpal row adapts to the deformity by forming an upside-down pyramid shape or triangle. Treatment depends on the age at presentation, degree of deformity, and magnitude of symptoms. Mild asymptomatic deformity warrants a period of nonsurgical management with serial x-ray examinations because the natural history is unpredictable. Many patients never require surgical intervention. Progressive deformity in the young child with considerable growth potential remaining requires release of Vickers ligament and radial physiolysis to prevent ongoing deterioration Concomitant ulnar epiphysiodesis may be necessary. Advanced asymptomatic deformity in older children with an unacceptable-appearing wrist or symptomatic deformity are indications for surgery. A dome osteotomy of the radius allows 3-dimensional correction of the deformity. Positive radiographic and clinical results after dome osteotomy have been reported.
Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
The skeletal dysplasias (or more appropriately, the osteochondrodysplasias) are genetic disorders that affect the development of the skeletal and cartilaginous tissues. They are of interest to the pediatric endocrinologist not only because most have an impact on linear growth causing short stature but also for what these disorders teach us about the mechanisms and regulation of growth.
Two individuals with bilateral Madelung's deformity were identified in a Late Intermediate period comingled tomb at the northern highland site of Marcajirca, Ancash, Peru (ca. AD 1250). Comparisons of the size and robusticity of the radii and ulnae suggest the individuals represent a male and a female. The difference in the severity of the changes is thought to represent variability in the expression of the deformity seen in males and females in clinical cases. Three comparatively short, thick tibiae were also recovered from this tomb, which may suggest that the individuals demonstrate Léri-Weill dyschondrosteosis, a type of dwarfism characterized by mesomelic shortening. These are the first examples of Madelung's deformity to be described from an archaeological context in South America and offer an insight into the use of tombs (chullpas) in Late Intermediate period Ancash.
In a survey of individuals with dwarfism in which 148 cases of typical achondroplasia were diagnosed, an additional group of 13 individuals was found to have an allied condition that was clearly a distinct entity. This is hypochondroplasia, a chondrodystrophy with roentgenographic changes similar to but milder than those of achondroplasia and without involvement of the skull. Hypochondroplasia is a heritable condition with autosomal dominant transmission. The diagnosis can only be established by roentgenographic examination.
Due to its critical location on the Nile River controlling trade from the south, Tombos is an important ancient site to explore the interaction between Egyptians and Nubians. To assess population continuity at Tombos through sociopolitical transitions, the appendicular skeleton of people from the New Kingdom and Napatan periods was examined. Using morphometric and statistical analyses, body proportions on the upper and lower limbs were studied on each element through size (i.e. length, breadth, and width) and shape (bone's measurements with size removed). The Napatan component (when Nubia ruled Egypt) was consistently larger in size than the earlier New Kingdom component (when Egypt ruled Nubia), with little variation in shape. More variability in both size and shape was observed in males. When compared with other Nubians (C‐group and Kerma) and Egyptians (Middle and New Kingdom), the Tombos Napatan sample (males and females) was generally larger, whereas the Tombos New Kingdom sample was generally smaller than other Nubians and similar in size to Egyptians. Some of the variability between the Tombos samples may be the result of gene flow, or rather changes in migration to the area through time and sociopolitics. However, the numerous differences in size with few in shape provide more support for an environmental explanation since size is more susceptible to nutritional stress, disease, and physical activity.
These results show that the people of Tombos underwent biological alterations during these major sociopolitical changes from Egyptian rule over Nubia during the New Kingdom to Nubia ruling Egypt during the Napatan period. This study also demonstrates that morphometric analyses of multiple bones and measurements are an important supplement to other bioarchaeological analyses to provide a broader of view of physical changes that occur over time. Copyright © 2014 John Wiley & Sons, Ltd.
Paleopathological cases of skeletal dysplasias (SD) are particularly interesting from a biological as well as biocultural perspective. Evidence of SD is relevant when discussing the antiquity of specific mutations, as well as the social perception of disease in the past. Here we propose a differential diagnosis for a Neolithic case of SD and discuss the possible social correlates of the observed condition. The subject of this study, a child with an age at death of about twelve years from the Late Neolithic site of Schweizersbild (Northern Switzerland), presents a bilateral shortening of the forearm and lower leg, with no further modifications affecting the cranial and postcranial skeleton. Morphological, metric, as well as radiographic analyses point to a diagnosis of Léri Weill dyschondrosteosis (LWD), making the present case the earliest known paleopathological example of this condition. From a biocultural perspective, the skeletal changes affecting the child, together with her/his relatively advanced age suggest active support from the community, providing new data to inform the debate on the cultural dimensions of disease in prehistory. This article is protected by copyright. All rights reserved.
An opportunity to explore osteological features of a form of disproportionate dwarfism is presented by a recent archaeological discovery. Excavation of a predominately nineteenth century Dutch cemetery from the rural, agricultural village of Middenbeemster revealed an older adult female with skeletal changes consistent with achondroplasia. The most marked features are a rhizomelic pattern of shortened and thickened upper and lower limbs, frontal bossing and a moderately depressed nasal bridge, small lumbar neural canals with short pedicles, bowing of the femora and tibiae, and short stature (130.0 ± 5 cm). However, some common features of achondroplasia like cranial base reduction and shortened fingers and toes are absent. The alternative diagnosis of a more mild form of short-limbed dwarfism, hypochondroplasia, is explored and aided by archival identification of the individual and her offspring. Five offspring, including three perinates, a 10-year-old daughter, and a 21-year-old son, are analysed for evidence of an inherited skeletal dysplasia. The unique addition of family history to the paleopathological diagnostic process supports a differential outcome of hypochondroplasia. This combination of osteological and archival data creates a unique opportunity to track the inheritance and manifestation of a rare disease in a past population.
Langer's mesomelic dysplasia is a rare cause of disproportionate dwarfism. The affected children have a normal intellect and life span and are usually seen later in life for management of skeletal deformities. The diagnosis is usually established on clinical and anthropometric analyses supported with relevant radiological investigations. Plain radiographs and full-length scanograms are sufficient in establishing the diagnosis. Further genetic studies are sometimes performed for confirmation, as Leri Weill dyschondrosteosis and Langer's mesomelic dysplasia are inherited because of mutations in the short stature homeobox (SHOX) gene. The literature is sparse with less than a hundred cases reported, and this case adds to the available data on this rare syndrome.
A rescue excavation at an early medieval Welsh cemetery has revealed rare evidence of an achondroplastic infant dwarf. The osteological examination revealed that the infant exhibited many characteristic features of dysplasia including proportionately short limbs, the early development of coxa vara and bowing tibia, whilst exhibiting normal trunk development. The exceptional preservation of such a good example of an achondroplastic infant will greatly contribute to the palaeopathological knowledge of this hereditary disease. Copyright © 2008 John Wiley & Sons, Ltd.
To describe genetic, clinical, anthropometric and radiological characteristics of 22 children with SHOX gene anomalies and familial short stature suggestive of Léri-Weill dyschondrosteosis.
Monocentric retrospective observational study.
Six children (27%) presented with deletions located downstream of SHOX (mean height -1.4 ± 0.9 SDS) and 16 (68%) with either deletions encompassing SHOX, intragenic deletions or point mutations of SHOX (mean patient height for the 3 latter types of anomalies: -2.6 ± 0.8 SDS). In our sample, the two most frequently observed dysmorphic signs were clinical and/or radiological Madelung deformity (86%) and high arched palate (77%). Half the girls were born small for gestational age. Sixteen children treated with recombinant growth hormone had an increase in height from -2.7 ± 0.7 to -1.4 ± 0.7 SDS. Four children achieved adult height (-2.0 ± 0.9 SDS) with a gain over baseline height of 1.0 ± 0.5 SDS after a mean treatment duration of 5.8 ± 2.1 years.
Patients shared common clinical, anthropometric and radiological signs but their height deficit varied, depending on the type of the SHOX gene anomaly. Due to the small size of our sample, our findings need to be confirmed in a larger population of patients.
The existence of dwarfism is amply documented in ancient Egypt due to the rich biological and artistic legacies. In previous articles published in this journal, I discussed the roles of people with skeletal dysplasia in ancient Egyptian civilization. In this article I, along with my Egyptian and American colleagues, describe two skeletons of dwarfs that date to 2700–2184 BCE and were unearthed from a funerary complex near the Great Pyramids in Giza. The first skeleton belongs to a high official, Per-ni-ankh-w, who died between 45 and 50 years of age. His statue is on display in the Egyptian Museum of Cairo. The second skeleton belongs to a pregnant female worker found with a fetus in situ. Her estimated age at death was 25–30 years. She most likely died during childbirth due to a small pelvic outlet as supported by her narrow sacrum. The fetal bones appear normal. Radiological examination of both skeletons confirmed the clinical diagnosis of achondroplasia.
Ancient Egyptians concerned themselves with the search for spiritual fulfillment through the tradition of moral teachings. Amenemope, a wise man who lived during the reign of Amenhotep III (1391–1354 BCE), advocated respect toward individuals with disabilities:
In summary, artistic, biological, and written resources indicate that dwarfs were well integrated in ancient Egyptian society.
SHOX deficiency is a frequent cause of short stature. The short stature homeobox-containing gene resides in the telomeric PAR1 region on the short arm of both sex chromosomes and escapes X inactivation. For this review, abstracts of 207 publications presented by PubMed for the search term 'SHOX' were screened. Heterozygote SHOX mutations (80% deletions) were detected in 2-15% of individuals with formerly idiopathic short stature, in 50-90% of individuals with Leri-Weill dyschondrosteosis, and in almost 100% of girls with Turner syndrome. Mutational analysis is primarily performed by MLPA analysis followed by gene sequencing if necessary. SHOX is a nuclear protein that binds to DNA and acts as a transcriptional activator. Orthologs are present in many vertebrates but not in rodents. Gene expression starting as early as 33 days postconception in humans is predominant in the mid portion of the buds and in the first and second pharyngeal arches. In the growth plate, hypertrophic chondrocytes express SHOX where it seems to have antiproliferative potency. The penetrance of SHOX deficiency is high, but its clinical expression is very variable becoming more pronounced with age and being more severe in females. Growth failure starts early during the first years of life and the height deficit present at preschool age seems not to deteriorate further. The mean adult height is -2.2 SDS. Auxological analysis of the body proportions (mesomelia), the presence of minor abnormalities, and the search for subtle radiographic signs are important keys to the diagnosis which has to be confirmed by genetic analysis. The growth-promoting effect of GH therapy approved for individuals with SHOX mutations seems to be equal to the effect seen in Turner syndrome.
The ancient Egyptians left an impressive artistic legacy documenting many aspects of their society including the existence of dwarfs as highly valued members. In previous publications in the Journal, I discussed dwarfs and skeletal dysplasia in ancient Egypt. In this study, I examined the ancient Egyptian representations of dwarfs of the Walters Art Museum in Baltimore, Maryland. One of the highlights of the collection is a group of five ivory figurines from Predynastic Times (pre 3500-3100 BCE) depicting a couple, a man with a child, and two females. Representations from other periods include ordinary as well as dwarf deities. The dwarf gods, Bes and Ptah, are frequently depicted holding or biting snakes or standing on crocodiles symbolizing their ability to ward off dangers. A couple of statuettes from the Greco-Roman Period that, in contrast to earlier Egyptian Periods, depict harsh physical anomalies, twisted bodies, and facial pain. The artistic impression can be interpreted as either tragic or humorous. The grotesque depiction of dwarfs during the Greco-Roman Period in ancient Egypt is believed to be due to a greater infusion of Hellenistic influence. This study provides a microcosm of the legacy of dwarfs in ancient Egypt and supports the premise that dwarfs were accepted and integrated in the ancient Egyptian society, and with a few exceptions, their disorder was not depicted as a physical handicap.
Most archaeologists and bioarchaeologists receive little or no training in the recognition of skeletal remains of fetuses, infants, and children. Yet many research sites may contain such materials. Without a framework for identifying the bones or the excavation techniques suited to their recovery, archaeologists may often overlook subadult skeletal remains or even confuse them with animal bones. The Osteology of Infants and Children fills the need for a field and lab manual on this important topic and provides a supplemental textbook for human osteology courses. Focusing on juvenile skeletons, their recovery and identification, and siding in both field and lab settings, the volume provides basic descriptions and careful illustrations of each skeletal element at varying stages of development, along with sections on differentiation from other bones and siding tips. The book offers detailed treatment of the skull and teeth, including the cranial vault and facial bones, and examines the infracranial skeleton: vertebrae, pelvis, chest, shoulders, arms, hands, legs, and feet. A quick reference guide explains age estimation and identification templates. The illustrations are enhanced by photographs from two recent archaeology projects in Egypt, at Abydos and Dakhleh Oasis. The extensive collection of fetal and child remains from these sites provides new reference material unavailable in previous publications, making this manual an unparalleled resource in the field of physical anthropology. Copyright © 2005 by Brenda J. Baker, Tosha L. Dupras, Matthew W. Tocheri, and Sandra M. Wheeler Manufactured in the United States of America. All rights reserved.
Mesomelic dwarfism encompasses several hereditary disorders of short stature with shortening most pronounced in the forearms and distal legs. One form, dyschondrosteosis, manifests as mesomelic shortening with Madelung deformity of the wrist and autosomal dominant inheritance. Another autosomal dominant disorder, hereditary nephritis, presents in early childhood as hematuria and proteinuria and commonly is associated with hearing loss and ocular abnormalities. This report describes a family in which both dyschondrosteosis and nephritis presented concurrently in several members of 4 consecutive generations. To the authors' knowledge this is a heretofore undescribed association of these 2 dominant syndromes.
IN 1878, MADELUNG (8) described a painful abnormality of the wrist and forearm which characteristically began in adolescence. The radiographic alterations of the radius and ulna were described later. The most complete review of the subject is that of Anton et al. (1), who collected and summarized the literature through 1938. Considering this clinical and radiographic abnormality a deformity rather than a syndrome, these workers distinguished it from Madelung's disease, which is characterized by diffuse symmetrical lipomatosis of the upper part of the back, shoulders, and neck. They also suggested that the deformity of the wrist and forearm be considered a dyschondroplasia of the distal radial epiphysis. While this may be a logical name for the entity, it has not found wide usage, Madelung's deformity remaining the preferred term. In 1929, Leri and Weill (7) reported a case of dwarfism and radiographic alterations of the forearm and wrist similar to Madelung's deformity, although no reference was made to M...
We report a boy with a new form of mesomelic dysplasia characterised by short stature, multifocal periosteal thickening, radio-humeral dislocation, osteoporosis and multiple fractures with minimal trauma. Electrophoresis of fibroblast collagens detected defects in type III and type V collagen.
Conclusion Bone dysplasias presenting with osteopenia, abnormal trabecular pattern, bone fragility, and periosteal thickening suggest a collagenopathy. A possible collagen defect requires biochemical investigations.
To evaluate the growth disorder and phenotype in prepubertal children with Leri-Weill dyschondrosteosis (LWD), a dominantly inherited skeletal dysplasia, and to compare the findings from girls with Turner syndrome (TS).
We studied the auxologic and phenotypic characteristics in 34 prepubertal LWD subjects (ages 1 to 10 years; 20 girls, 14 boys) with confirmed short stature homeobox-containing gene (SHOX) abnormalities. For comparative purposes, we evaluated similar physical and growth parameters in 76 girls with TS (ages 1 to 19 years) and 24 girls with LWD (ages 1 to 15 years) by using data collected from the postmarketing observational study, GeNeSIS.
In the clinic sample LWD subjects, height standard deviation score ranged from -5.5 to +0.1 (-2.3 +/- 1.3, girls and -1.8 +/- 0.6, boys). Wrist changes related to Madelung deformity were present in 18 of 34 (53%) LWD subjects. In comparing the LWD and TS populations in the GeNeSIS sample, Madelung deformity, increased carrying angle, and scoliosis were more prevalent in the LWD population, whereas high arched palate was similarly prevalent in the two populations.
Short stature is common in both LWD (girls and boys) and TS (girls). Clinical clues to the diagnosis of SHOX haploinsufficiency in childhood include short stature, short limbs, wrist changes, and tibial bowing.
Ancient Egypt was one of the most advanced and productive civilizations in antiquity, spanning 3000 years before the "Christian" era. Ancient Egyptians built colossal temples and magnificent tombs to honor their gods and religious leaders. Their hieroglyphic language, system of organization, and recording of events give contemporary researchers insights into their daily activities. Based on the record left by their art, the ancient Egyptians documented the presence of dwarfs in almost every facet of life. Due to the hot dry climate and natural and artificial mummification, Egypt is a major source of information on achondroplasia in the old world. The remains of dwarfs are abundant and include complete and partial skeletons. Dwarfs were employed as personal attendants, animal tenders, jewelers, and entertainers. Several high-ranking dwarfs especially from the Old Kingdom (2700-2190 BCE) achieved important status and had lavish burial places close to the pyramids. Their costly tombs in the royal cemeteries and the inscriptions on their statutes indicate their high-ranking position in Egyptian society and their close relation to the king. Some of them were Seneb, Pereniankh, Khnumhotpe, and Djeder. There were at least two dwarf gods, Ptah and Bes. The god Ptah was associated with regeneration and rejuvenation. The god Bes was a protector of sexuality, childbirth, women, and children. He was a favored deity particularly during the Greco-Roman period. His temple was recently excavated in the Baharia oasis in the middle of Egypt. The burial sites and artistic sources provide glimpses of the positions of dwarfs in daily life in ancient Egypt. Dwarfs were accepted in ancient Egypt; their recorded daily activities suggest assimilation into daily life, and their disorder was not shown as a physical handicap. Wisdom writings and moral teachings in ancient Egypt commanded respect for dwarfs and other individuals with disabilities.
Trotter and Gleser's (Trotter and Gleser: Am J Phys Anthropol 10 (1952) 469-514; Trotter and Gleser: Am J Phys Anthropol 16 (1958) 79-123) long bone formulae for US Blacks or derivations thereof (Robins and Shute: Hum Evol 1 (1986) 313-324) have been previously used to estimate the stature of ancient Egyptians. However, limb length to stature proportions differ between human populations; consequently, the most accurate mathematical stature estimates will be obtained when the population being examined is as similar as possible in proportions to the population used to create the equations. The purpose of this study was to create new stature regression formulae based on direct reconstructions of stature in ancient Egyptians and assess their accuracy in comparison to other stature estimation methods. We also compare Egyptian body proportions to those of modern American Blacks and Whites. Living stature estimates were derived using a revised Fully anatomical method (Raxter et al.: Am J Phys Anthropol 130 (2006) 374-384). Long bone stature regression equations were then derived for each sex. Our results confirm that, although ancient Egyptians are closer in body proportion to modern American Blacks than they are to American Whites, proportions in Blacks and Egyptians are not identical. The newly generated Egyptian-based stature regression formulae have standard errors of estimate of 1.9-4.2 cm. All mean directional differences are less than 0.4% compared to anatomically estimated stature, while results using previous formulae are more variable, with mean directional biases varying between 0.2% and 1.1%, tibial and radial estimates being the most biased. There is no evidence for significant variation in proportions among temporal or social groupings; thus, the new formulae may be broadly applicable to ancient Egyptian remains.
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