Growth and Growth Hormone through the Ages: Art and Science.

BACKGROUND: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval. SUMMARY: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones. KEY MESSAGES: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.

A case of dwarfism in 6th century Italy: Bioarchaeological assessment of a hereditary disorder.

OBJECTIVE: The skeletal remains of a short-statured individual (T17) are described and a differential diagnosis performed to determine the etiology of the condition. MATERIALS: An individual considered pathologically short in stature was discovered in the burial site of Piazza XX Settembre, Modena (northern Italy). METHODS: Morphological and morphometric analyses were performed, and T17 was compared to dwarfs from other localities and periods and to the adult female population from the same site. A paleopathological survey was undertaken to assess the degree of the skeletal elements of T17 were affected. RESULTS: T17 was a female, 20-30 years of age at death, with a stature of 128 cm and disproportionate dwarfism associated with congenital skeletal dysplasia. CONCLUSIONS: T17 likely affected by a form of hypochondroplasia. SIGNIFICANCE: Anatomical consequences of hypochondroplasia are presented, and the timeframe and associated burial goods suggest a 6th-century Lombard short stature belonging to one of the earliest Lombard settlements in Italy. SUGGESTIONS FOR FURTHER RESEARCH: Future genetic analysis would resolve if the mutation in the type 3 fibroblast growth factor receptor (FGFR3) is present in the remains of T17; however, it is not exclusivly linked to hypochondroplasia.

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.

Genetics in the art and art in genetics.

"Healing is best accomplished when art and science are conjoined, when body and spirit are probed together", says Bernard Lown, in his book "The Lost Art of Healing". Art has long been a witness to disease either through diseases which affected artists or diseases afflicting objects of their art. In particular, artists have often portrayed genetic disorders and malformations in their work. Sometimes genetic disorders have mystical significance; other times simply have intrinsic interest. Recognizing genetic disorders is also an art form. From the very beginning of my work as a Medical Geneticist I have composed personal "algorithms" to piece together evidence of genetics syndromes and diseases from the observable signs and symptoms. In this paper we apply some 'gestalt' Genetic Syndrome Diagnostic algorithms to virtual patients found in some art masterpieces. In some the diagnosis is clear and in others the artists' depiction only supports a speculative differential diagnosis.

[The bodies of dwarfs in Italian art during the Renaissance]. / Le corps des nains dans l'art italien de la Renaissance.

Agnolo Bronzino's painting of Nano Morgante depicts for the first time the anatomy of a dwarf. This image testifies Cosimo's special interest for this dwarf. In Antonio Francesco Grazzini's poem written in Nano Morgante's honor, we underline some interesting aspects of his physical deformities and his small height, which are highly praised as we can see them on the painting.

Falsehood on the move. The Aztec children and science in the second half of the 19th century.

Allegedly kidnapped from a secret city in Central America, the "Aztec children" began a showman's career in the early-1850s. They died around 1900, after being observed by countless pathologists and ethnologists from Europe and the US. Most of the literature on the "Aztec children" has emphasized racial theories, the imperial gaze, and the character of "ethnological shows", where monstrosity and ethnicity were practically synonymous. Less attention has been paid to the fact that scientists continuously insisted that the case was false, an argument that instead of debunking the myth of the "Aztec children", contributed to establishing the "Aztecs" as "a matter of fact". In examining the case of the "Aztec children", this essay aims to explore what can be called the shifting nature or elusiveness of falsehood.

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.