Julia Dahlkamp, MSc, PhD
King's College London, United Kingdom

 

Thomas Sydenham,
1688 Mary Beale
National Portrait Gallery, London

Introduction  

In recent years the genre of the written medical case report1 has come to be regarded as unscientific, a form of anecdotal evidence low in the hierarchy of studydesigns.2 Clinical geneticists, on the other hand, have emphasized its unique quality, as a single observation can offer an understanding that may be generalizable.3 Indeed the genre has survived.1 Why? Because the case study has the explicitly stated purpose of educating, warning, and furthering scientific knowledge. To this may be added a note of mystery and curiosity, balanced with dramatic and theatrical interest.2 A single case study of Huntington's Disease can be substantiated by analyzing a selection of case reports from the past 100 years,3 highlighting how the mystery and drama of genetic case reports may account for the continued success of this literary genre.4

The demise and rise of the written case report

Although case reports go back to the Hippocratic era, the written case report in its current form is a highly composed literary genre dating to Thomas Sydenham in the 17th century.4  By 1980, an obituary for case reports could have been written as many journals declared them to be superfluous. Since then the BMJ has found that the clinical case report fills a void left by larger clinical studies.5 Others have been written in its defense, arguing that it complements clinical research6 and helps create recognition patterns.7 Now, case reports are published in most established journals, and even specific case journals have been newly created.8

Three scientific strategies for survival – and one less scientific

Specified criteria for when a case is worthy of publication9 can arguably be subsumed to educating about a disease, warning about adverse effects and unexpected outcomes, learning from the mistakes of others, or reading about a new diagnostic procedure or treatment.  But mystery and drama interest are additional factors, such as in the ‘medical mysteries’ published by New England Journal of Medicine (NEJM)10 or "myth exploded" and unusual presentation of a more common disease in BMJ. Another example is that neurological case reports are overrepresented in the BMJ, the NEJM, and the medical TV drama House MD. Thomas concludes that neurological cases make for a "gripping yarn" because of the diversity of symptoms, greater emotional resonance, and dramatic twist.11 Thus mystery and drama, though implicit and hidden between the lines, are always present in case reports.

Clinical genetics as refuge

Huntington’s Disease (HD), described in the late 19th century, offers all the ingredients of mystery and drama. It was and sometimes still is a clinical diagnosis with clinico-anatomical diagnostic tests available, albeit with variable reliability. Clinical case reports go back more than a century and roughly represent four periods: developments after first description (around 1900), after the recognition and discovery of DNA (after 1945), shortly before the discovery of the gene (around 1980), and after availability of a test (from roughly 2000 on).

The symptoms of HD, now known as a progressive autosomal-dominant neurodegenerative disorder with a distinct phenotype, were first described by George Huntington in 1872.12  In his 1900 series, Good lists 22 reports of "chorea," each describing related family members with the same condition.13 Goods language is brief, exact and scientific, and yet he makes poignant remarks:

John C. was 37 at the time of his death. … The disease began without any exciting cause. … This patient’s great-great-grandmother, his great-grandmother, his grandmother and his mother were choreic, his mother developing the disease at 30 and dying at 40. (p. 26)

This seemingly factual description also encompasses aspects of the author’s interest ("exciting cause") and medical drama in the description of the family history. Good’s scientific writing shows awareness for the drama of the family history of HD as well as curiosity for the fascinating and fatal aspects. Likewise, Rusk published a single case report with an extensive autopsy report.14 Thus, case reports at around 1900 most importantly establish HD as a diagnostic entity, but express marked sympathy for the doomed families as well as excitement at the rare mysterious nature of the disease.

With regard to the second period, (around 1945), single case reports15 illustrating methods of predictive diagnosis become relevant. For example, Patterson tried to establish a predictive test for EEGs using case reports.16 The development of eugenics becomes apparent.17 While furthering knowledge is still the explicit aim, the tragic mystery of children is now focused upon increasingly, as there is growing interest in the juvenile onset of HD.18

At around 1980, thirdly, now that the diagnostic category of HD is firmly established, more "unusual" symptoms such as  rigidity are being reported.19 Yet authors continue to figure themselves into the text admitting to be "hesitant" to diagnose a disease with such a fatal prognosis (p. 573). Further focus is also placed on psychiatric rather than somatic symptoms.20 HD in children remains very prevalent in case reports, one case report ending with the poignant note "[s]ince writing this report the sister of Case 1, now aged 5 years, has developed signs of HD."21 Generally, HD is recognised as a family drama22 – resulting in case reports focussing  on family counselling,23 but also in recognizing broader issues such as child welfare.24 While case reports still broaden the diagnostic category, the family drama and especially dying children still dominate the case report.

Lastly, for the period from roughly after 1995, one might expect that interest in case reports would subside after the genetic mechanism and the protein is discovered and a test becomes available. But the opposite seems to occur. Case reports increase, and the drama continues in the form of unusual presentations (association with an eating disorder),25 juvenile onset,26 or rare constellations such as large intergenerational variation of onset or different phenotypic expression monozygotic twins.27,28

Thus all these reports over the past century have been used to educate, warn, or further expand knowledge, by first establishing HD as a stable disease entity and subsequently by reporting new or unusual symptoms. But fascination for the medical drama and mystery of the disease continues, particularly in clinical genetics. Still the clinical detective: the mystery and the drama as balancing effects

First, the mystery. There is frequent reference in the literature to the close link between medical science and Holmesian detective work.29,30 Rarely is this element spelled out as explicitely as by Vanderbroucken, who writes: "[C]ase reporting … is great fun. Like much of medical reasoning, it has a detective-like quality."31 Likewise, recent publications quite openly combine the clinical case and the detective story in their title: "The Simpson–Golabi–Behmel syndrome: A clinical case and a detective story"32 or in an article published shortly before the discovery of the Huntington gene: "Huntington disease: a detective story."33 This is emphasised by portrayals of "gene detectives" in popular culture.34

An explanation for the prevalence of mystery in clinical genetics could be that it remains a specialty of the rare and novel, unusual presentations or late diagnosis, the unexplained. The following recent examples of case reports might serve as exemplary proof: In the case of the "Extremely rare pseudotrisomy 13," the reason for the report is given in the title, the use of "extremely" toying with expectations and alluding to a curious audience.35 Similarly, some case reports could have been published by Sir Conan Doyle himself: "The man with the leontine facies" clearly alludes to detective stories and, again, intentionally fosters curiosity in a potential reader.36

But the medical detective, like the cold deductionist Holmes, needs an empathic Watson in order to function. Enter, the medical drama. Both HD and DMD are still fatal genetic conditions, where clinical genetics cannot cure the disease. It can however – less in the sense of a spectacle, but rather in the sense of emotional attendance – get insight in a family history, a narrative that is dramatically influenced by a diagnosis.

In medical education, curiosity-provoking and emotional clinical cases have been found memorable and helpful in forming pattern recognition.37 Why should the newly minted medical doctor hand over curiosity, emotional involvement in medical drama, and fascination for mystery in exchange for a medical diploma? On the contrary, curiosity crystallized in a fascination for the mysterious and interest in the human medical drama should be fostered and kept alive. In the case report, the implicit figuring in of medical mystery and drama provides a tool to foster medical curiosity, which is why this unique literary genre is alive and kicking.

References

  1. John C. Carey, ‘Significance of Case Reports in the Advancement of Medical Scientific Knowledge’, American Journal of Medical Genetics Part A, 140A:19 (2006), 2131-2134.    
  2. John C. Carey, ‘A Species Not Extinct: Publication of Case Reports and Scientific Knowledge’, American Journal of Medical Genetics Part A, 140A:8 (2006), 801-803.  
  3. J. M. Opitz et al., ‘Terminological, Diagnostic, Nosological, and Anatomical-Developmental Aspects of Developmental Defects in Man’, Advances in Human Genetics, 9 (1979), 71-164.    
  4. Brian Hurwitz, ‘Form and Representation in Clinical Case Reports’, Literature and Medicine, 25.2 (2006), 216-240 (p. 227).    
  5. Michael Kidd and Charlotte Hubbard, ‘Introducing Journal of Medical Case Reports’, Journal of Medical Case Reports, 1.1 (2007), 1-2.    
  6. Jan P. Vandenbroucke, ‘In Defense of Case Reports and Case Series’, Annals of Internal Medicine, 134.4 (2001), 330-334.    
  7. Heather A. Carleton and Matthew L. Webb, ‘The Case Report in Context’, The Yale Journal of Biology and Medicine, 85.1 (2012), 93-96.    
  8. N. H. Abu Kasim et al., ‘The Current Status of the Case Report: Terminal or Viable?‘, Biomedical Imaging and Intervention Journal, 5.1 (2009), 1-4.    
  9. Michael Kidd and Charlotte Hubbard, ‘Introducing Journal of Medical Case Reports’, Journal of Medical Case Reports, 1.1 (2007), 1-2.    
  10. Ralf Ostermaier and Marianne Taut, ‘Medical Mystery – 50 Years of Medical Progress’, New England Journal of Medicine, 352.14 (2005), 1473.    
  11. Rhys H. Thomas and Naomi J. P. Thomas, ‘House Calls: The Case of the Entertaining Case’, British Medical Journal, 339 (December 2009), 1416-1417.   
  12. George Huntington, ‘On Chorea’, Archives of Neurology, 17.3 (1967), 332-333.    
  13. Clarence A. Good, ‘A Review of Chronic Progressive Chorea (Huntington's), with Report of a Case’, American Journal of Psychiatry, 57.1 (1900), 21-38. All further references to this edition are given after quotations in the text.    
  14. Glanville Y. Rusk, ‘A Case of Huntington's Chorea with Autopsy’, American Journal of Psychiatry, 59.1 (1902), 63-82.    
  15. Simon M. Lesse, ‘Huntington's Chorea Report of a Case’, The Journal of Nervous and Mental Disease, 104.1 (1946), 84-87.    
  16. Ralph M. Patterson, B. K. Bagchi and Avery Test, ‘The Prediction of Huntington's Chorea an Electroencephalographic and Genetic Study’, American Journal of Psychiatry, 104.12 (1948), 786-797.    
  17. Charles B. Davenport, ‘Huntington's Chorea in Relation to Heredity and Eugenics’, Proceedings of the National Academy of Sciences of the United States of America, 1.5 (1915), 283-285.    
  18. Eugene I. Falstein and Theodore T. Stone, ‘Juvenile Huntington's Chorea’, Archives of Neurology and Psychiatry, 45.1 (1941), 151-155.    
  19. George A. Perrine Jr and Richard M. Goodman, ‘A Family Study of Huntington's Chorea with Unusual Manifestations’, Annals of Internal Medicine, 64.3 (1966), 570-574. All further references to this edition are given after quotations in the text.    
  20. Susan E. Folstein and others, ‘The Association of Affective Disorder with Huntington’s Disease in a Case Series and in Families’, Psychological Medicine, 13.3 (1983), 537-542.    
  21. John P. Osborne, P. Munson and D. Burman, ‘Huntington's Chorea. Report of 3 Cases and Review of the Literature’, Archives of Disease in Childhood 57.2 (1982), 99-103.    
  22. Susan E. Folstein, Huntington's Disease : A Disorder of Families (Baltimore: Johns Hopkins University Press, 1989).    
  23. Audrey Tyler and P. S. Harper, ‘Attitudes of Subjects at Risk and Their Relatives Towards Genetic Counseling in Huntington's Chorea’, Journal of Medical Genetics, 20.3 (1983), 179-188.    
  24. Brian Martindale and Virginia Bottomley, ‘The Management of Families with Huntington's Chorea: A Case Study to Illustrate Some Recommendations’, Journal of Child Psychology and Psychiatry, 21.4 (1980), 343-351.    
  25. Sara Marconi and others, ‘Eating Disorder as a Psychiatric Onset of Juvenile Huntington's Disease’, American Journal of Psychiatry, 168.10 (2011), 1120-1121.   
  26. Francis A. Nahhas and others, ‘Juvenile Onset Huntington Disease Resulting from a Very Large Maternal Expansion’, American Journal of Medical Genetics Part A, 137.3 (2005), 328-331.    
  27. Elke Holinski-Feder and others, ‘Large Intergenerational Variation in Age of Onset in Two Young Patients with Huntington's Disease Presenting as Dyskinesia’, Pediatrics, 100.5 (1997), 896-898.    
  28. M. H. Anca and others, ‘Different Phenotypic Expression in Monozygotic Twins with Huntington Disease’, American Journal of Medical Genetics Part A, 124.1 (2003), 89-91.    
  29. P. L. Selvais, ‘A Study in White: Dr. Watson in the Medical Press’, Journal of the Royal Society of Medicine, 89.6 (1996), 329-331.    
  30. A. K. Oderwald and J. H. Sebus, ‘The Physician and Sherlock Holmes’, Journal of the Royal Society of Medicine, 84.3 (1991), 151-152.    
  31. Vandenbroucke, p. 333.    
  32. F. Gurrieri et al., ‘The Simpson – Golabi – Behmel Syndrome: A Clinical Case and a Detective Story’, American Journal of Medical Genetics Part A, 155.1 (2011), 145-148.    
  33. F. V. Schaefer, M. Floyd, and B. Say, ‘Huntington Disease: A Detective Story’, The Journal of the Oklahoma State Medical Association, 85.5 (1992), 223-226.    
  34. Rebecca Coombes, ‘Profile: The Gene Detective’, British Medical Journal, 336.7644 (2008), 586-587.    
  35. Mehmet Davutoglu et al., ‘Extremely Rare Syndrome: Pseudotrisomy 13’, Journal of Medical Cases 3.3 (2012), 193-194.    
  36. M. R. Siddiqui and F. M. Siddiqui, ‘A Man with Leonine Facies’, BMJ Case Reports (2012), <doi:10.1136/bcr.10.2011.5057>.    
  37. Charles G. Prober and Chip Heath, ‘Lecture Halls without Lectures‚ a Proposal for Medical Education’, New England Journal of Medicine, 366.18 (2012), 1657-1659.

Bibliography

Abu Kasim, N. H., et al., ‘The Current Status of the Case Report: Terminal or viable?‘, Biomedical Imaging and Intervention Journal, 5.1 (2009), <doi: 10.2349/biij.5.1.e4>
Anca, M. H., and others, ‘Different Phenotypic Expression in Monozygotic Twins with Huntington Disease’, American Journal of Medical Genetics Part A, 124.1 (2003), 89-91
Bayoumi, Ahmed M., and Peter A. Kopplin, ‘The Storied Case Report’, Canadian Medical Association Journal, 171.6 (2004), 569-570.
Carey, John C., ‘A Species Not Extinct: Publication of Case Reports and Scientific Knowledge’, American Journal of Medical Genetics Part A, 140A:8 (2006), 801-803
Carey, John C., ‘Significance of Case Reports in the Advancement of Medical Scientific Knowledge’, American Journal of Medical Genetics Part A, 140A:19 (2006), 2131-2134
Carleton, Heather A., and Matthew L. Webb, ‘The Case Report in Context’, The Yale Journal of Biology and Medicine, 85.1 (2012), 93-96
Coombes, Rebecca, ‘Profile: The Gene Detective’, British Medical Journal,336.7644 (2008), 586-587
Davenport, Charles B., ‘Huntington's Chorea in Relation to Heredity and Eugenics’, Proceedings of the National Academy of Sciences of the United States of America, 1.5 (1915), 283-285
Davutoglu, Mehmet, et al., ‘Extremely Rare Syndrome: Pseudotrisomy 13’, Journal of Medical Cases 3.3 (2012), 193-194
Falstein, Eugene I., and Theodore T. Stone, ‘Juvenile Huntington's Chorea’, Archives of Neurology and Psychiatry, 45.1 (1941), 151-155
Folstein, Susan E., and others, ‘The Association of Affective Disorder with Huntington’s Disease in a Case Series and in Families’, Psychological Medicine, 13.3 (1983), 537-542
Folstein, Susan E., Huntington's Disease : A Disorder of Families (Baltimore: Johns Hopkins University Press, 1989)
Good, Clarence A., ‘A Review of Chronic Progressive Chorea (Huntington's), with Report of a Case’, American Journal of Psychiatry, 57.1 (1900), 21-38
Gurrieri, F., et al., ‘The Simpson – Golabi – Behmel Syndrome: A Clinical Case and a Detective Story’, American Journal of Medical Genetics Part A, 155.1 (2011), 145-148
Holinski-Feder, Elke, and others, ‘Large Intergenerational Variation in Age of Onset in Two Young Patients with Huntington's Disease Presenting as Dyskinesia’, Pediatrics, 100.5 (1997), 896-898
Huntington, George, ‘On Chorea’, Archives of Neurology, 17.3 (1967), 332-333.
Hurwitz, Brian, ‘Form and Representation in Clinical Case Reports’, Literature and Medicine, 25.2 (2006), 216-240 (p. 227)
Kidd, Michael, and Charlotte Hubbard, ‘Introducing Journal of Medical Case Reports’, Journal of Medical Case Reports, 1.1 (2007), 1-2
Lesse, Simon M., ‘Huntington's Chorea Report of a Case’, The Journal of Nervous and Mental Disease, 104.1 (1946), 84-87
Marconi, Sara, and others, ‘Eating Disorder as a Psychiatric Onset of Juvenile Huntington's Disease’, American Journal of Psychiatry, 168.10 (2011), 1120-1121.
Martindale, Brian, and Virginia Bottomley, ‘The Management of Families with Huntington's Chorea: A Case Study to Illustrate Some Recommendations’, Journal of Child Psychology and Psychiatry, 21.4 (1980), 343-351
Nahhas, Francis A., and others, ‘Juvenile Onset Huntington Disease Resulting from a Very Large Maternal Expansion’, American Journal of Medical Genetics Part A, 137.3 (2005), 328-331
Oderwald, A. K., and J. H. Sebus, ‘The Physician and Sherlock Holmes’, Journal of the Royal Society of Medicine, 84.3 (1991), 151-15
Opitz, J. M., et al., ‘Terminological, Diagnostic, Nosological, and Anatomical-Developmental Aspects of Developmental Defects in Man’, Advances in Human Genetics, 9 (1979), 71-164
Osborne, John P., P. Munson and D. Burman, ‘Huntington's Chorea. Report of 3 Cases and Review of the Literature’, Archives of disease in childhood 57.2 (1982), 99-103
Ostermaier, Ralf, and Marianne Taut, ‘Medical Mystery – 50 Years of Medical Progress’, New England Journal of Medicine, 352.14 (2005), 1473
Patterson, Ralph M., B. K. Bagchi and Avery Test, ‘The Prediction of Huntington's Chorea an Electroencephalographic and Genetic Study’, American Journal of Psychiatry, 104.12 (1948), 786-797
Perrine, George A. Jr, and Richard M. Goodman, ‘A Family Study of Huntington's Chorea with Unusual Manifestations’, Annals of Internal Medicine, 64.3 (1966), 570-574
Prober, Charles G. and Chip Heath, ‘Lecture Halls without Lectures‚ a Proposal for Medical Education’, New England Journal of Medicine, 366.18 (2012), 1657-1659
Rusk, Glanville Y., ‘A Case of Huntington's Chorea with Autopsy’, American Journal of Psychiatry, 59.1 (1902), 63-82
Schaefer, F. V., M. Floyd, and B. Say, ‘Huntington Disease: A Detective Story’, The Journal of the Oklahoma State Medical Association, 85.5 (1992), 223-226
Selvais, P. L., ‘A Study in White: Dr. Watson in the Medical Press’, Journal of the Royal Society of Medicine, 89.6 (1996), 329-331
Siddiqui, M. R., and F. M. Siddiqui, ‘A Man with Leonine Facies’, BMJ Case Reports (2012), <doi:10.1136/bcr.10.2011.5057>
Rhys H. Thomas and Naomi J. P. Thomas, ‘House Calls: The Case of the Entertaining Case’, British Medical Journal, 339 (December 2009), 1416-1417
Tyler, Audrey, and P. S. Harper, ‘Attitudes of Subjects at Risk and Their Relatives Towards Genetic Counselling in Huntington's Chorea’, Journal of Medical Genetics, 20.3 (1983), 179-188
Vandenbroucke, Jan P., ‘In Defense of Case Reports and Case Series’, Annals of Internal Medicine, 134.4 (2001), 330-334
Wexler, Alice, ‘Stigma, History, and Huntington's Disease’, The Lancet, 376.9734 (2010), 18-19

 


JULIA DAHLKAMP, MSc, PhD went to medical school at the University of Heidelberg, where she was awarded her PhD in medicine in 2011. She then went on to Oxford University to study Medical Anthropology. Since 2012, she has been a Wellcome Trust scholar at the Centre for Humanities and Health and studying for a Master's degree in Medical Humanities at King's College London.