Wall paintings facies and their possible genetic correlates in the ancient Pompeii: A bio-anthropologic message from the past?

Research paper

Wall paintings facies and their possible genetic correlates in the ancient

Pompeii: A bio-anthropologic message from the past?

Giovanni Ponti

⁎

, Marco Manfredini

, Cristel Ruini

a

Department of Surgical, Medical, Dental and Morphological Sciences with Interest transplant, Oncological and Regenerative Medicine, Dermatology Unit, University of Modena and Reggio Emilia, Modena 41124, Italy

b

Department of Dermatology, Staedtisches Klinikum Muenchen, Munich, Germany c

Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany d

Department of Surgical, Medical, Dental and Morphological Sciences with Interest transplant, Oncological and Regenerative Medicine, Clinical Pathology Unit, University of Modena and Reggio Emilia, Modena, Italy

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 23 February 2016

Received in revised form 16 April 2016 Accepted 18 April 2016

Available online 20 April 2016

Thefigurative arts and precisely the ancient Pompeian wall paintings portraits can provide an additional source of information in supplementing bio-anthropological studies. There are several genetic diseases with a wide spectrum of congenital bone stigmata in association to distinctive facial features. Gorlin–Goltz syndrome, also named nevoid basal cell carcinoma syndrome, is an autosomal dominant syndrome characterized by unusual skeletal changes, such as macrocephaly, facial asymmetry, hypertelorism, frontal and parietal bossing caused by germline mutations of the gene PTCH1. The Gorlin syndrome, clinically defined in 1963, existed during Dynas-tic Egyptian times, as revealed by a spectrum of skeletalfindings compatible with the syndrome in mummies dat-ing back to three thousand years ago and, most likely, in the ancient population of Pompeii. In the present research, we discuss the potential relationship between Pompeian wall paintings portrait and the cranio-metric bone changes revealed among the Pompeian skull collections assuming that the ancient portraits can constitute an important tool that should be strictly integrated with osteologic and biomolecular data in order to argue a syndromic diagnosis in ancient population.

© 2016 Elsevier B.V. All rights reserved. Keywords:

Wall paintings portrait Gorlin–Goltz syndrome NBCCS Skeletal anomalies PTCH1 NBCCS history Pompeii 1. Introduction

Figurative art is closely linked to disease through disease affecting subjects of paintings. There are several examples of artists that have portrayed genetic disorders and malformations in their work (Bukvic and Elling, 2015). A special setting of wall paintings ancient portraits have been collected during the excavation of Pompeii, Herculanem, and Stabia. The well-preserved wall paintings found in Pompeii can pro-vide an additional source of information about Pompeian bio-anthropologic studies. Not only mythological scenes were depicted, but also several local models enriched the colored representations of daily life on the paintings. The faces of many effective members of the local society settled the walls of the city; being portrayed by a local artist already signaled a high status quo. See for example the wall painting portraits of Pasquius Proculis and his wife, which is emblematic of

local models in Pompeian pictures (Pappalardo, 2001, 2004, 2007) (Fig. 1).

The role offigurative arts in supplementing bio-anthropological studies had already been hypothesized by Giustiniano Nicolucci, the founder of the Institute of Anthropology of the University of Naples, in the 19th century; the Italian anthropologist examined the portraits on the walls of the Pompeian domus to obtain useful information that could complement his anthropometric studies on the recently discov-ered ostheological collections. Nicolucci was the author of thefirst offi-cial publication on the human skeletal remains of Pompeii published in 1882. He included a plate of lithographs in his work, which described as “faithful reproduction” of facies from Pompeian wall paintings. Regard-ing the Pompeian skull collection, he stated that“some skulls were glob-ular, other ovoid and a few were oblong in form”; the last type of skull observed in this work was interpreted as of African origin, probably be-longing to the slaves at the service of the wealthy citizens of Pompeii. Nicolucci described the population of Pompeii in 79 AD as heteroge-neous, but mainly autochthonous (Nicolucci, 1882).

Carefully examining the anatomical features of the skulls in the collection, Nicolucci observed“lack or minimal protrusion of the frontal sinuses_{” and described it as the typical trait of the “Pompeian type,” for} which he noticed that“the top of the frontal bone was observed to gener-ally take a more or less ogival or pointed arch form” (Fig. 2). The idea of a

Abbreviations: AD, Anno Domini; NBCCS, Nevoid basal cell carcinoma syndrome; CT-scan, Computer tomography.

⁎ Corresponding author at: Via del Pozzo n. 71, Department of Surgical, Medical, Dental and Morphological Sciences with Interest transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, 41124, Italy.

E-mail address:giovanni.ponti@unimore.it(G. Ponti).

http://dx.doi.org/10.1016/j.gene.2016.04.038

0378-1119/© 2016 Elsevier B.V. All rights reserved.

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heterogeneous but mainly autochthonous population diverged from the previous study of the anthropologist Stefano Delle Chiaie, who theorized in 1853 the presence of multiple ethnical groups in the city of Pompeii. The assertions of Delle Chiaie were based on the historical reports that narrated the conspicuous amount of slaves of African or Eastern descent among the most humble locals (Delle Chiaie, 1854).

More anthropological studies have focused on the craniometrical features of the osteological collections hoarded in the archeological site of Pompeii (D'Amore, 1979; Laser, 2011). The modern 3D computer tomography applied to the study of molds and cranial skeletal segments have recently started to contribute to a better anthropometric charac-terization (Abate et al., 2004); in particular, CT-scan could improve the estimation of craniometrical indexes and hereby the reproduction of a“Pompeian facies” through facial reconstruction tools. The field of digital reconstruction involves both scientific and artistic techniques that are able to recreate accurate reproductions of soft-tissues

components in a human face, starting from a naked skull. Although fas-cinating, these modern techniques cannot produce a reliable picture of the original human face, because of the lack of available information about soft tissues. However, also reconstruction studies documented the frontal bone stigmata mentioned above (Abate et al., 2004).

With the advent of paleogenetics and paleopathology, researchers aim to the genetic and genomic characterization of the osteological samples. The analysis of mitochondrial and nuclear DNA sequences that already contributes to determine the parental relationships (Di Bernardo et al., 2009) might also play a role in confirming a clinical diagnosis based on the skeletal stigmata.

2. Skull features and Gorlin–Goltz Syndrome stigmata in the Pompe-ii osteologic collection

Several genetic syndromes present distinctive skeletal semeiological signs; for example, facial asymmetry, hypertelorism, frontal and parietal bossing typically affect the facies of patients carrying a germline muta-tion of PTCH1 gene. This genetic signature belongs to patients with Gorlin–Goltz syndrome, also named nevoid basal cell carcinoma syn-drome (NBCCS), and features an autosomal dominant systemic disease with almost complete penetrance and high intra-familial phenotypic variability. NBCCS is an uncommon disease, with estimated prevalence of 1/57,000 to 1/256,000, that is clinically diagnosed when a constella-tion of signs are identified, in particular in the presence of a) two major criteria, b) one major criteria and the molecular confirmation, or c) one major and two minor criteria. Major criteria are excessive number of basal cell carcinomas, odontogenic keratocysts, palmoplantar pits, calci_{fication of the falx cerebri, medulloblastoma and first-degree} relative with Gorlin–Goltz syndrome. Minor criteria are rib anomalies, other specific skeletal malformations and radiologic changes (i.e. verte-bral anomalies, kyphoscoliosis, short 4th metacarpals, postaxial poly-dactyly), macrocephaly, cleft lip and/or palate, ovarian/cardiac fibroma, lymphomesenteric cysts, ocular abnormalities (Table 1) (Larsen et al., 2014).

The combination of concomitant skeletal abnormalities in multiple anatomic sites of involvement is an important aid to the diagnosis of

Fig. 1. Wall paintings portrait of Paquius Proculo and his wife. In this picture, a detailed representation of the committee is provided with realistic traits.

Fig. 2. Pictures of selected skull acquired at the Sarno Baths archeological skeletal collection of Pompeii, showing the typical NBCCS-associated alterations. Reproduced with the permission of the Special Superintendence for the Archaeological Remains of Pompeii.

NBCCS, which can be made when at least one major and two minor criteria are satisfied (Gorlin and Chaudhary, 1960; Gorlin et al., 1963; Lo Muzio et al., 2013). The skeletal semeiological signs that characterize NBCCS phenotype, such as the presence of frontal and parietal bossing, macrocephaly and calcifications of the falx cerebri, are the result of the corresponding alterations of the neuro- and splanchnocranium dur-ing the embryonic development (Fig. 2) and are an important clue for the clinical diagnosis of NBCCS.

As usually happening in the history of science, the Gorlin–Goltz syn-drome was clinically defined as a specific entity in 1960 [9] but was

almost certainly present in the human race at the times of the ancient Egyptians (Boano et al., 2006; Ponti et al., 2014). The statement is based on a spectrum of skeletal_{findings compatible with the syndrome} found in mummies dating back to three thousand years ago and, most likely, in the skeletal collection of the ancient population of Pompeii and Herculaneum (Ponti et al., 2014).

A previously published study at the University of Modena and Reg-gio Emilia, in collaboration with the Special Superintendence of the ar-chaeological remains of Pompei, was conducted in order to characterize the clinical features of the skeletal remains collected in the Forum Baths from Pompeii archaeological site. The anthropometric analysis of the skeletal remains was aimed to the identification of the likely presence of hereditary syndromes (especially the Gorlin syn-drome) affecting the roman population in A.D. 79. The specific aim of the study was the identification of the skeletal alteration characteristic of the NBCCS (Ponti et al., 2016).

At the archaeological bone collection of Pompeii, our recent analysis conducted on the about 200 skulls stored in both the Forum Baths and Sarno Baths allowed to de_{fine a significant heterogeneity of the} anthro-pometric cranial parameters as such as a vast percentage of dolicocranic skulls with some individuals having hyperdolicocranic skulls. It was among the dolicocranic and hyperdolicocranic portion of the population that some skulls presented different non-metric traits, such as fronto-parietal bossing and macrocephaly, characteristics of the NBCCS (Fig. 2). This observation, of a high frequency of macrocephaly and fron-tal bossing in the population of Pompeii, lead us to hypothesize that dif-ferent individuals of the Pompeii population were affected by NBCCS. Considering the rarity and the low frequency of the syndrome, it is high-ly improbable that all specimens of frontal bossing observed in the

Table 1

Clinical diagnostic criteria for NBCCS.

NBCCS clinical diagnosis: a) two major criteria, b) one major criteria and molecular confirmation, or c) one major and two minor criteria.

Major criteria

1. Excessive numbers of basal cell carcinomas 2. Odontogenic keratocysts of the jaws (b20 years old) 3. Palmar or plantar pitting

4. Calcification of the falx cerebri 5. Medulloblastoma

6. First-degree relative affected Minor criteria

1. Rib anomalies

2. Other specific skeletal malformations and radiologic changes 3. Macrocephaly

4. Cleft lip and/or palate 5. Ovarian/cardiacfibroma 6. Lymphomesenteric cysts 7. Ocular abnormalities

Fig. 3. (a) Wall paintings portrait of young man from Pompei restoration laboratory; (b) boy dead prematurely represented as Adone; House of Successus, Pompei; (c)“Male portrait” on glass (I secolo d.C.), from Pompei. Napoli, Museo Nazionale inv. 132,424 (foto AFP MN 1369); (d–e–f) Wall paintings portraits of women with syndrome-like facial characteristics, from Villa dei Misteri, Pompei.

osteological collections are due to a genetic defect. It is therefore to pos-tulate that this somatic trait of the frontal bones was common in the original Pompeian population as a characteristicfinding. This hypothe-sis can be evaluated by the analyhypothe-sis of the somatic traits of wall paintings and mosaic portrait of Pompeian local models.

3. The contribution of wall paintings portrait to bio-anthropologic studies

Not only Nicolucci and Delle Chiaie, but also the previous superin-tendent of Pompei Prof. Conticello saw in the Pompeian portraits an im-portant resource for the integration of anthropometric analysis. His studies focused on the wall paintings from Villa of P. Fannius Synistor in Boscoreale (Conticello, 1987).

There has been debate within the scientific community concerning the effective percentage of reality and idealization in the portrayed faces; although, it is difficult to ascertain whether Pompeian paintings represent real portraits or idealized images, in our opinion various wall paintings of local models showed frontal bossing and mild macrocephaly.

Our analysis of different portraits (Figs. 1,3,4) highlights the presence of numerous examples of frontal and supraorbital bossing of individuals of both genders, a fact that reflects the data observed in the macroscopical examination of skulls belonging to the local collec-tions. The famous portrait of a Pompeian man depicted on an oval glass is emblematic of the well-documented frontal bossing on the skulls collected in the Pompeian osteological collection (Fig. 3c). Local portraits from Herculaneum and Stabia share common distinctive facial traits, in particular regarding the frontal region (Fig. 4). The same cranio-facial features can be deduced even by some sculptures and coins of Roman emperors which showed familial frontal bossing traits (Fig. 5).

A major limit in diagnosing syndromical criteria osteological collec-tions is represented by the disarticulated nature of the samples, as it is for the Pompeian ones. Even though isolated skull anomalies do not lead unequivocally to the NBCCS diagnosis, the high frequency of the syndromic abnormalities in the dolichocranic population represents an important clue to hypothesize that at least some individuals were af-fected by NBCCS. In particular, some skulls were afaf-fected by marked frontal and parieto-occipital bossing asymmetry of the cranial base, and presence of multiple odontogenic cysts in the mascellary bone (signs already described by Gorlin in 1963). The analysis of the corre-sponding mandibles and ribs would be of great scientific value, but unfortunately, it was not possible to match all of them with their skulls. In fact, even though frontal bossing is an important criteria for NBCCS recognition, in the specific setting of the ancient roman population, it

Fig. 4. (a) Wall painting portraits of man with distinctive frontal traits from Stabia. (b) Wall painting portrait of a young man showing distinctive frontal traits from Herculaneum. Both wall paintings portraits are exposed at the National Museum of Naples.

Fig. 5. Sculptures and coins of a dynasty of Roman emperors showing typical NBCCS cranio-facial stigmata: (a) Gordonio I, sculpture; (b) Gordonio I, coin; (c) Gordonio II, sculpture; (d) Gordonio II, coin; (e, f) Gordonio III, sculpture.

probably should be associated to other main cranio-facial criteria in order to establish a clinical NBCCS diagnosis. The relatively high fre-quency of skull anomalies in the ancient Pompeiian population should be critically interpreted; in fact, not all frontal bossings are necessarily associated to NBCCS or genetic diseases. If we consider the estimated prevalence of NBCCS, we would expect a presence of maximal 1_–2 cases in the Pompeiian population of the time, while we noticed the cranio-facial features in at least 3–4 skulls and numerous portraits. Of course, the prevalence of the syndrome could have been diluted over the centuries, thanks to the increasing genetic exchanges. Moreover, it is possible that other genetic scenarios have been responsible for the examined cranio-facial phenotypes. For example, the portrait showed inFig. 3d might be shown in a description of Holt–Oram syn-drome, which is characterized by frontal bossing, triangular face, micrognathia, down-slanting palpebral fissures, hypertelorism, low-set ears (Lichiardopol et al., 2007). Additionally, we could also take the example of Noonan syndrome, with ocular hypertelorism, epicanthal folds, ptosis, micrognathia, depressed nasal root, and low-set, posteriorly rotated ears (pinnae). Another disorder that might be taken into account in the series of differential diagnosis of frontal bossing is Hyperostosis Frontalis Interna (HFI), which is char-acterized by bilateral, symmetrical deposits of bone overgrowth on the inner table of the frontal bone. The HFI wasfirst documented in the medical literature 300 years ago and was then associated to the clinical disorder known as Stewart–Morel–Moore syndrome (May et al., 2010). This condition usually occurs in elderly females and may be associated with a disorder in hormonal balance (Hershkovitz et al., 1999). Laser E. assumed the incidence of HFI in the Pompeian popula-tion with an approximate prevalence of 11.1–11.9%, since 43 out of 360 analyzed skulls showed HFI features (Laser, 1996). The same author additionally described a portrait found in the House of Adonis, where the represented individual, probably Hermaphrodites, displays clinical signs of HFI (Fig. 6).

4. Conclusion

The anthropometric data evinced from the local osteological collec-tions can be correlated to the facial features of local Pompeian wall por-traits, which usually reflect the common traits in the population of the time, as well as the esthetics canons. These considerations can be used

to formulate hypothesis on the presence of specific genetic syndromes in past centuries, where medicine was moving itsfirst steps and was far away from imaging genetic sequencing.

The relatively high frequency of frontal bossing in wall painting por-traits should be critically interpreted in order to argue an NBCCS pheno-type among the ancient population. It is highly improbable that NBCCS is responsible for all facial modifications displayed in the portraits, since the prevalence is estimated around 1/57,000–1/256,000 (at least in con-temporary times). Our scientific imagination can, however, be captured by many other syndromes sharing frontal bossing with the phenotype described by Gorlin, for example, Noolan syndrome, Holt–Oram syn-drome, Crouzon synsyn-drome, Hurler synsyn-drome, Pfeiffer synsyn-drome, Rubin-stein–Taybi syndrome, Russell–Silver syndrome, HFI, and many others. We shouldn't forget the changing in esthetic canons and the ability of the local artists as confounding factors. However, when associated to the hypertelorism and facial asymmetry, the feature may be in favor of a NBCCS. This would change our data regarding the prevalence of these syndromes, that reflect the actual data but do not take into account the reduced genetic variability of populations in ancient times.

What we should remember is that wall paintings and other forms of portraying the indigenous human features (such as sculptures and mo-saics) represent a rich source of scientific data, when correlated to the human remains. In particular, the correlation of local portraits and oste-ological collections may help to reconstruct the bio-anthroposte-ological in-formation and to assume the presence of distinct congenital diseases in the ancient times. Future aims will be the determination of the muta-tional status of PTCH1, after the laboratory procedures of ancient DNA extraction. PTCH1 gene sequencing from ancient DNA, extracted from distinct skulls and/or mummified bodies, might be able to allow the NBCCS biomolecular diagnosis and a phylogenetic analysis as well as a study of founder effects of the mutations.

Acknowledgments

We thank Prof. Massimo Osanna (general director of Pompei Soprintendence), and Dr. Ernesto De Carolis, the head of the Applied Biology Laboratory of Pompei. We thank Prof. Umberto Pappalardo (Suor Orsola Benincasa University) for his contribution regarding the acquisition and analysis of some wall painting cited in the manuscript.

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