Two cases of skeletal dysplasia from New Kingdom (c. 1400-1050 BCE) Tombos, Sudan.

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.

Gene cloning to clinical trials-the trials and tribulations of a life with collagen.

This review, based on the BSMB Fell-Muir Lecture I presented in July 2018 at the Matrix Biology Europe Conference in Manchester, gives a personal perspective of my own laboratory's contributions to research into type X collagen, metaphyseal chondrodysplasia type Schmid and potential treatments for this disorder that are currently entering clinical trial. I have tried to set the advances made in the context of the scientific technologies available at the time and how these have changed over the more than three decades of this research.

Overlapping genetic pathways in the skeletal dysplasias of a middle woodland individual: A case study.

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.

The smallest of the small.

Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) II has recently been defined as a PCNT gene defect. Historically, it has been a disorder of interest because of the severe intrauterine growth restriction and postnatal short stature. The very shortest/smallest mature human being undoubtedly had this disorder. Maria Zarate lived between 1864 and 1890 and traveled in sideshows to England and all over North America. Her exceeding short stature was well documented in photographs and by a group of physicians in England. She was Mexican and also had an affected brother. A museum, Museo Casa Grande, about her still exists in Cempoala, Mexico.

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.

Nasu-Hakola disease: The first case reported by Nasu and review: The 50th Anniversary of Japanese Society of Neuropathology.

Nasu-Hakola disease (NHD) was first reported separately by Nasu and Hakola around the same time in the 1970s. It is an autosomal recessive inherited disorder characterized by progressive dementia and repeated pathological fractures during adolescence. It has recently been demonstrated that NHD is caused by a mutation in the TREM2 or DAP12 gene. The present paper demonstrates the first patient reported by Nasu and reviews NHD. The patient was a man who died at the age 38 years. His family history was unremarkable. There was no abnormal developmental history. At the age of 26, the patient suffered a pathological fracture of the right tibia, and X-ray confirmed bone resorption in the right tibia. As for mental status, the patient tended to be euphoric. After that, bone resorption was also seen in other long bones. At the age of 33, the patient could not walk after suffering a right femoral neck fracture. He was apathetic and exhibited behavioral abnormalities. At the age of 38, he could not move or speak and subsequently died. General pathological examination showed yellow opaque gelatinous substances in the medullary cavities, matching translucent cystic lesions in the femur, tibia, and fibula on X-rays. Light microscopy showed numerous membranocystic changes in the substances. The brain weighed 1050 g. Symmetric systemic cerebral atrophy, in particular atrophy of the cerebral white matter in the occipital and temporal lobes, was confirmed. Histological examination showed white matter degeneration and diffuse sclerosis accompanied by astroglial proliferation. Severe demyelination was confirmed. Axonal degeneration and destruction were marked. In demyelinated areas, fat granule cells appeared, and lipid granule-positive cells aggregated around vessels. Cerebral cortical neurons were relatively maintained. In the brain, no membranocystic lesions could be recognized. In the DAP12 gene, the patient had a conversion of nucleotide at position 116 resulting in serine 38 to asparagine substitution.

Possible case of spondylo-epiphyseal dysplasia in a medieval skeleton.

Multiple anomalies of vertebral and long bone growth were observed in the incomplete skeleton of an adult male from a collection of 693 medieval skeletons excavated at Abingdon, Oxfordshire. The skeleton consists of a fragmented skull, right scapula and humerus, left humerus, radius, ulna and partial hand, vertebrae from C1 to T11, and fragments of the ribs and sternum. The bones were examined, measured, and radiographed. The humeri are abnormally short and thick, with exaggerated muscle attachments. Both shoulder joints show extensive osteoarthritic destruction. Some vertebrae show slight flattening of the bodies, and there is possible evidence of both kyphosis and scoliosis. Skull, forearm, and hand bones are of normal size and morphology. Lack of lower limb bones and abnormal proportions in the upper limbs prevent meaningful estimation of stature. However, the other features of the skeleton are consistent with a diagnosis of spondylo-epiphyseal dysplasia. No other skeletons displaying similar anomalies were observed.

Dwarfism and gigantism in historical picture postcards.

A collection of 893 historical picture postcards from 1900 to 1935, depicting dwarfs and giants, was analysed from medical and psychosocial viewpoints. In conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis was more difficult because of heterogeneity. The most common conditions depicted were pituitary dwarfism and achondroplasia. Most of those with gigantism had pituitary gigantism and acromegaly. Brothers and sisters or parents and their children provided evidence of mendelian inheritance of some of these disorders. The cards suggest that being put on show provided, at least in some cases, social benefits.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. II: Skeletal dysplasias.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than five thousand specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies was recatalogued and redescribed according to contempory syndromological views. The original descriptions, as far as preserved, were compared with the clinical and radiographical findings. In 18 specimens the following skeletal dysplasias were diagnosed: achondrogenesis, achondroplasia, Blomstrand chondrodysplasia, Majewski syndrome, osteodysplastic primordial dwarfism, osteogenesis imperfecta type I, osteogenesis imperfecta type II, and thanatophoric dysplasia with and without cloverleaf skull. Radiography did not yield a diagnosis in 4 specimens. The use of additional diagnostical techniques, such as MRI and CT scanning and fluorescence in situ hybridization in these specimens, is currently being investigated.

A case of chondrodystrophic dwarfism in the Italian late Upper Paleolithic.

During excavations by P. Graziosi at Romito Cave near Papasidero (Cosenza) in Calabria, Italy, two skeletons (Romito 1 and 2) were discovered in a common grave. Although the specimens were briefly described by Messeri (Atti X Riuniuone Scientifica Ist. Ital. Preist. Protost., pp. 301-307, 1966), it is generally unknown in the anthropological literature that one of these individuals is a chondrodystrophic dwarf. As such, the specimen provides the earliest known case of dwarfism in the human skeletal record, extending the time span of this genetically determined growth abnormality to approximately 10,000 years ago. The specimen (Romito 2) exhibits features typical of chondrodysplasia, including a high domed skull, compressed cranial base, and in the postcranial skeleton extremely shortened diaphyseal lengths. The unique combination of these features suggests this pathological condition is acromesomelic dysplasia. Besides providing evidence for a greater antiquity of dwarfism than previously known, the fact that this individual reached late adolescence attests to tolerance of Upper Paleolithic groups for severely abnormal individuals and their ability to support members who were of limited economic value to the social group.