Pycnodysostosis: the disease of Henri de Toulouse-Lautrec.

Pycnodysostosis or Maroteaux-Lamy syndrome is a genotypic bone disorder, with autosomal recessive inheritance, individualized by Lamy and Maroteaux in 1962. It is characterized by diffuse condensation of the skeleton with thickening of the cortex and narrowing of the medullary cavity. This condensation is reminiscent of the one observed in Albers-Schönberg disease, which differs essentially in dysmorphism of the skull (no closure of fontanelles, gaping sutures, hypoplasia of the lower jaw with open mandibular angle) and extremities (hypoplasia or osteolysis of the phalanges). The patients have a short stature, short hands and feet, and malformed nails. The first scientifically correct diagnosis was made by Dr. G. Séjournet who, under the guidance of his teacher Professor J.-A. Lièvre, performed extensive research and diagnosed Henri de Toulouse-Lautrec with achondroplasia-related dwarfism. This article describes pycnodysostosis and reports the life of the painter Henri de Toulouse-Lautrec who died from the disease.

Trabecular bone microarchitecture analysis, a way for an early detection of genetic dwarfism? Case study of a dwarf mother's offspring.

A 66 year-old woman with a disproportionate dwarfism and who bore seven children was discovered at the Middenbeemster archaeological site (The Netherlands). Three are perinates and show no macroscopic or radiological evidence for a FGFR3 mutation causing hypo-or achondroplasia. This mutation induces dysfunction of the growth cartilage, leading to abnormalities in the development of trabecular bone. Because the mutation is autosomal dominant, these perinates have a 50% risk of having been affected. This study determines whether trabecular bone microarchitecture (TBMA) analysis is useful for detecting genetic dwarfism. Proximal metaphyses of humeri were µCT-scanned with a resolution of 7-12 µm. Three volumes of interest were segmented from each bone with TIVMI© software. The TBMA was quantified in BoneJ© using six parameters on which a multivariate analysis was then performed. Two of the Middenbeemster perinates show a quantitatively different TBMA organization. These results and the family's medical history suggest a diagnosis of genetic dwarfism for this two perinates. This study provides evidence to support the efficacy of µCT for diagnosing early-stage bone disease.

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.

Artistic representations of short stature, a tentative diagnosis.

Throughout human history, disease-related short stature has represented a source of fascination. Following the recent advances in genetics and molecular biology, several hundreds of possible causes are now to be considered. We present herein a few examples of the diagnosis approach of such cases from art sources (sculptures, paintings or photographs for the most recent periods), associated or not with biographical data, allowing semiological and anthropological analyses. The explored period spans from antic great civilizations to 19th Century Western societies. The palaeopathological diagnosis method is based upon medical approach. It includes a search for possible associated abnormalities and the distinction between proportioned, mainly related to hormonal disorders (particularly growth hormone deficiency), and non-proportioned cases especially associated with genetic skeletal dysplasias. Among this latter category, achondroplasia is the most represented cause of short stature. Other more exceptional etiologies are also reported.

Pseudoachondroplasia and the seven Ovitz siblings who survived Auschwitz.

This historical report focuses on the first clinical description of pseudoachondroplasia and its radiographic findings. Only half a century ago, pseudoachondroplasia was recognized as a genetic disorder with a distinct but variable phenotype of short stature, normal facial features, and progressive joint problems starting in adolescence. Radiologically, the disease is particularly intriguing because the patients appear normal at birth. The patients develop the typical gait disturbances when they begin to walk. Radiographs show the characteristic anterior tongue-shaped lumbar vertebral body changes that develop after the first year of life. This account presents the most well-known group of individuals affected by pseudoachondroplasia, the Ovitz family, who narrowly escaped death in the concentration camp of Auschwitz in 1944 because of SS physician Dr. Josef Mengele's fascination with dwarfs. It was not until 1995 that the underlying genetic defect in the COMP gene was identified on chromosome 19.

Genetic drift. The ancient Egyptian dwarfs of the pyramids: the high official and the female worker.

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: Do not jeer at a blind man nor tease a dwarf, Neither interfere with the condition of a cripple. Do not taunt a man who is in the hand of God, Nor scowl at him if he errs. In summary, artistic, biological, and written resources indicate that dwarfs were well integrated in ancient Egyptian society.

From Horus the child to Hephaestus who limps: a romp through history.

The question of why Hephaestus, the Greek god of smiths, limped has been the subject of much debate, mainly on mythological grounds. This debate extended also into the field of medical diagnosis, with attempts at defining the nature of the deformity that made the crippled Hephaestus the buffoon of the other Olympic gods. One problem encountered in these debates was the changes to which the ugly young Hephaestus was subjected with the passing of time-from a limping deformed youth to the later dignified and normal man. While some authors, largely influenced by poetic Greek texts and vase paintings, attributed the limp to talipes (club-feet), others pointed to certain features suggestive of achondroplasia. Since the image of the early Hephaestus is based mainly on the much earlier concept of the Egyptian god Ptah, who as the triune god of the resurrection sometimes is depicted as an achondroplastic dwarf (Ptah-Pataikos), the suggestion of the possible achondroplastic dwarf-like nature of the early Hephaestus is not implausible. It is supported by similarities in the image of Hephaestus to some features in other Egyptian gods, such as the domestic god Bes, the guardian of the new-born, and the Horus the Child or Harpocrates (Greek), yet another protector of youth and "the symbol of everything that is young and vigorous" [Budge, 1969: The Gods of the Egyptians, or Studies in Egyptian Mythology. Volume I.]. The characteristic feature of this child-god is the "lock of Harpocrates" on the right side of his head. That this lock can sometimes also be seen not only on the head of Ptah-Pataikos and of Bes but also on the young Hephaestus is highly suggestive of the Egyptian influence on his image. Recently, however, another interesting explanation of Hephaestus's limp has been suggested that may explain why the Egyptian influenced image of the early achondroplastic Hephaestus changed to the later, more Grecian view of the smith-god who hobbled because of club-feet. Improvements in composition-analysis of samples from antique statues and various utensils have led to the suggestion that the introduction of new smelting techniques in antique times may have exposed ancient metal workers to the effects of various toxic metals causing, for instance, chronic lead poisoning or, more relevant here, chronic arsenic poisoning causing peripheral neuritis with weakness and lameness of one or both lower extremities. Later changes in smelting technique, and recognition or guess-work of a possible connection between these techniques and toxic effects, may explain the change from the buffoon-like achondroplastic walk to the club-footed limp and eventual normal behaviour of Hephaestus, the Smith. In other words: Did Hephaestus limp because of his arsen-neuritis?

A brief journey into medical care and disease in ancient Egypt.

Ancient Egypt was one of the greatest civilizations to have arisen, becoming the cradle of scientific enquiry and social development over 3 millennia; undoubtedly its knowledge of medicine has been vastly underestimated. Few artefacts survive which describe the medical organization, but from the extent of the diseases afflicting that ancient populus there would have been much to study. Evidence from papyri, tomb bas reliefs and the writings of historians of antiquity tell of an intense interest in the sciences, humanities and medicine born of an educated society which had overcome the superstitions of its nomadic ancestors.

Historical case of dwarfism: attempted diagnosis.

A brief description is given of a male dwarf painted by the Italian artist Geromo Induno in 1852. This portrayal seems not to have been mentioned previously in the medical literature. Several experts were consulted in an attempt to diagnose the underlying skeletal dysplasia. Most opted for pseudoachondroplasia, with the most detailed argument coming from the subject of this Festschrift.

Bes, Aesop and Morgante: reflections of achondroplasia.

The past perception of achondroplasia is reflected in art, beginning about 2000 B.C. Achondroplasia is thought to have provided a model for the representation of a series of figures including the Egyptian god Bes, the Greek teller of fables Aesop, and the Renaissance giant of fiction Morgante. Since these figures were basically viewed as good, the hypothesis is advanced that achondroplasia was perceived as a positive, not a negative, condition during at least part of the past four millenia.

[Osteoarticular diseases from J.M. Charcot to the present time]. / Les affections ostéo-articulaires de J.M. Charcot à nos jours.

In foreign countries Charcot's main contribution in the field is known as Charcot's joint. A special paper is devoted to this topic by Dr Hubault in this issue of the Revue. It is perhaps less widely known that Charcot's thesis was devoted to rheumatoid arthritis and that he wrote also interesting observations on gout. Pierre Marie gave many famous contributions to bones and joints diseases. In 1886 he described acromegaly. In 1890 he described hypertrophic pulmonary osteoarthropathy which he correctly linked with lung diseases although some of the cases he had collected in the literature were instances of pachydermo-periostosis. In 1900 he gave a brilliant description of achondroplasia in 2 of his patients: Anatole and Claudius. On the 11th of February 1898 he reported 2 patients which were the basis of a historical description of ankylosing spondylitis, on which papers by Strümpell and von Bechterew had appeared in 1884 and 1893. The subsequent works at the Clinique des Maladies du Système Nerveux de la Salpêtrière on sciatica and herniated disks are related in Professor de Seze's paper in this issue of the Revue.