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Differential Diagnosis of Complex Conditions in Paleopathology: a Mutational Spectrum Approach by Elizabeth Lukashal a Thesis

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Differential Diagnosis of Complex Conditions in Paleopathology: a Mutational Spectrum Approach by Elizabeth Lukashal a Thesis Differential Diagnosis of Complex Conditions in Paleopathology: A Mutational Spectrum Approach by Elizabeth Lukashal A thesis presented to the University of Waterloo in fulfillment of the thesis requirement for the degree of Master of Arts in Public Issues Anthropology Waterloo, Ontario, Canada, 2021 © Elizabeth Lukashal 2021 Author’s Declaration I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public. ii Abstract The expression of mutations causing complex conditions varies considerably on a scale of mild to severe referred to as a mutational spectrum. Capturing a complete picture of this scale in the archaeological record through the study of human remains is limited due to a number of factors complicating the diagnosis of complex conditions. An array of potential etiologies for particular conditions, and crossover of various symptoms add an extra layer of complexity preventing paleopathologists from confidently attempting a differential diagnosis. This study attempts to address these challenges in a number of ways: 1) by providing an overview of congenital and developmental anomalies important in the identification of mild expressions related to mutations causing complex conditions; 2) by outlining diagnostic features of select anomalies used as screening tools for complex conditions in the medical field ; 3) by assessing how mild/carrier expressions of mutations and conditions with minimal skeletal impact are accounted for and used within paleopathology; and 4) by considering the potential of these mild expressions in illuminating additional diagnostic and environmental information regarding past populations. iii Acknowledgements I would like to thank Dr. Maria Liston for taking an early interest in my research and agreeing to act as my supervisor. I am grateful for your time and guidance throughout this process, as well as the opportunities you have provided. Thank-you also to Dr. Jane Buikstra for your feedback and support early on and for your participation on the committee. Thank- you to Dr. Alexis Dolphin as well, for your advice and for your time as a committee member. Also, thank-you to the Department of Anthropology, especially Dr. Jennifer Liu and Dr. Adrienne Lo for all their efforts during the coursework to cater to a group of students with very different interests. As always, my family has been a great support and I would like to thank them for the many evenings they spent listening to me talk about the trials and tribulations of diagnostics in paleopathology. I appreciate their patience and wisdom. Thank-you to my fellow classmates for making a difficult and unprecedented COVID-19 year better with your humour and support. I have also received generous financial support from the Iris Yuzdepski family through the Iris Yuzdepski award, and the Sally Weaver Memorial Fund for which I am extremely grateful. iv Table of Contents Author’s Declaration ................................................................................................................. ii Abstract .................................................................................................................................... iii Acknowledgements .................................................................................................................. iv List of Tables ........................................................................................................................... vi List of Figures .................................................................................................................. vii-viii Chapter 1 Relevance to the Public & Reasoning for Venue Choice ...................................... 1-6 1.1 Introduction ...................................................................................................................... 1-2 1.2 Definitions of Public Issues Anthropology ...................................................................... 2-3 1.3 Biomedical Approaches to Complex Conditions ............................................................. 3-6 1.4 Proposed Publication Venue ............................................................................................... 6 Chapter 2 Differential Diagnosis of Complex Conditions in Paleopathology: A Mutational Spectrum Approach ............................................................................................................. 7-49 2.1 Introduction .................................................................................................................. 7-9 2.2 Definitions .................................................................................................................. 9-10 2.3 Congenital Anomalies vs Variants ........................................................................... 10-11 2.4 Changing Approaches to Differential Diagnosis ..................................................... 11-14 2.5 Methods and Materials ............................................................................................. 14-16 2.6 Results ...................................................................................................................... 16-49 2.6.1 Mild Expressions in Differential Diagnosis ...................................................... 16-18 2.6.2 Anomalies Associated with Mild Skeletal Expressions .................................... 18-19 2.6.3 Mild Anomalies of the Hands, Feet, and Phalanges .......................................... 20-29 2.6.4 Anomalies of the Dentition................................................................................ 29-36 2.6.5 Anomalies of Ear Structure and Choanal Atresia .............................................. 36-42 2.6.6 Joint Laxity ........................................................................................................ 42-46 2.7 Discussion .................................................................................................................... 46-49 Bibliography ...................................................................................................................... 50-71 Appendix ............................................................................................................................ 72-99 v List of Tables Table 1: Most frequently noted conditions as suggested final diagnoses in paleopathological case study sample .................................................................................................................... 17 Table 2: List of suggested final diagnoses and differential diagnoses of case studies with shortened 4th metacarpals ........................................................................................................ 29 Appendix Table 1: List of conditions selected as final suggested diagnoses .................... 72-74 Appendix Table 2: Congenital Anomaly Recording Form (Adapted from Castriota- Scanderbeg & Dallapiccola 2005; Shapira et al. 2019; Miles et al. 2008) ........................ 75-95 Appendix Table 3: Brachydactyly, Polydactyly (Short/Hypoplastic/Extra metacarpals, Metatarsals and Phalanges) and Associated Anomalies (data collected from Minozzi et al. 2015; Garcia & Santos 2019; Satinoff & Wells, 1969; Ponti et al., 2016; Kozieradzka- Ogunmakin, 2011; Cybulski 1988; Cormier et al. 2017; Lieverse et al. 2008; Museum of London, Wellcome Osteological Database, Bermondsey Abbey; Roberts et al. 2004) .... 96-97 Appendix Table 4: Dental Agenesis and Associated Anomalies (data collected from (Usher et al. 2000; Curate 2008; Laffranchi et al. 2015; Tur et al. 2017; Arriaza et al. 2019) .............. 98 Appendix Table 5: Anomalies of the Ear Structure and Associated Anomalies (data collected from Panzer et al. 2008; Hoffman et al. 2019; Knusel et al. 1996; Kesterke & Judd 2019; Vairamuthu & Peiffer 2018; van Duijvenbode et al. 2015; Keenleyside 2011; Pany & Teschler‐Nicola 2007; Swanston et al. 2013) ......................................................................... 99 vi List of Figures Figure 1: Summary of anomalies connected to known mild expressions of complex conditions. Adapted from Orphanet (2020); Stelzer et al. (2003); Bergendal (2014); Lexner (2007); Jaruga et al. (2016); Teber et al. (2004); Passos-Bueno et al. (2009); Davids et al. (1990); Singh et al. (2015); Weber & Kousseff (1999) .......................................................... 19 Figure 2: Examples of excavation/outcarving of the middle phalanx (i, ii) and asymmetry of the trochlea (ii) (modeled after Giedion 1998, 756) ............................................................... 23 Figure 3: Types of brachydactyly type E and related anomalies associated with syndromes (adapted from Pereda et al. 2013, Orphanet 2020) ................................................................. 24 Figure 4: Anomalies known to be present with brachydactyly type E in relation to specific syndromes (adapted from Pereda et al. 2013; Orphanet 2020) ............................................... 25 Figure 5: Skeletal anomalies of X-linked hypohidrotic ectodermal dysplasia and carrier (adapted from Bergendal 2014; Lexner 2007; García-Martín et al. 2011; Bailleul-Forestier et al. 2008; Orphanet 2020) ........................................................................................................ 33 Figure 6: Skeletal anomalies of hypohidrotic ectodermal dysplasia
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