The natural history of a clinical geneticist

A future clinical geneticist bugs her parents to buy her the marine biology book she saw in the bookstore window because those otherworldly creatures with see-through blood capture her imagination. She is besotted by biology in fourth grade and by chemistry in seventh grade, followed by the human biology course in the last year of public school. She studies her mother's tattered Encyclopedia of Health as if it were her personal Bible so that on her final exam in eighth grade biology she describes the eye in such a meticulous detail she does not have time to answer other questions. But in case that she does not get into medical school she bets on her two greatest interests—chemistry and biology—and majors in biochemistry. Only hard science courses hold her interest; there is no time for poetry, for the humanities. In biochemistry, she is enchanted by how DNA is made and how it replicates. She learns the Krebs cycle by heart and relishes the intricacies of biochemical pathways: both the major thruways and the tiny dark alleys. In fact, the more obscure the enzyme and its cofactor, the better. In medical school it is medical biochemistry that captivates the future geneticist—it starts with galactosemia. Why does a single disease cause liver dysfunction, cataracts, and intellectual disability? What is the common denominator? She starts to collect unusual and wonderful associations—Kallman syndrome: anosmia and hypogonadism; Alport syndrome: hearing loss and kidney failure. Her brain gloms onto these seemingly random associations and she can not shake them off. She decides to become a pediatrician—she does not want to look after adults and the elderly, and neither surgery—too much like a trade—nor psychiatry interest her. But biochemistry and pediatrics? What a strange combination. Almost like those diseases that fascinate her. The future clinical geneticist experiences her epiphany during the second-year medical school genetics course. It is all about unusual conditions that occur rarely and are difficult to diagnose. Most of the patients are children. And many of the diseases are biochemical. There is even a subspecialty—metabolic genetics—that seems custom-tailored. She has found her destiny. The genetics course director demands that, on their exams, future doctors explain genetic concepts in sixth grade language, as if they were talking to patients who have never taken any biology courses. The future geneticist's classmates are ready to mutiny—they did not strive to acquire the arcane language of science only to give up its secrets to just any Tom, Dick, and Harry. Plus it is hard to explain the double helix structure and DNA replication in layman's terms. She does not know yet that is what genetic counselors do everyday, that this is the bread and butter of genetic practice, but she understands the method behind the director's madness. So she learns to explain DNA and patterns of human inheritance in layman's terms. And she really enjoys doing it. And then there are the times when the budding clinical geneticist stares at the black and white photographs in old genetics atlases. Compendia of human misery, she thinks of them at the time. A short man with his arms and legs disproportionately short and thick, flesh bunched up above his knees and elbows, as if there were too much of it, as if as a fetus he grew his skin several size too large for his skeleton. Bulging forehead, deep-set eyes; the head too large for his neck that looks too frail to support it. Pages and pages of photos—the more difficult the photo, the more mesmerized she becomes. She does not know what fascinates her. Photos of bilateral cleft lip, the premaxillary process pulled up to reveal misaligned teeth, and a view into the nasal cavity do not upset her anymore, nor do cleft eyelids with bulging, unprotected eyes. She is upset when she sees a cloverleaf skull with proptosed eyes for the first time, but that passes after she looks at the photo a few times. Exposure desensitization. By the time she is a consultant and sees children so affected she will not be so bothered. She will congratulate their parents on their births. A question a colleague had to answer on his fellowship interview: “When does a malformed human being stop being human?” Only one answer: Never. The future clinical geneticist finishes medical school and her pediatrics residency. Now that she is training to be a geneticist she has developed a habit of flipping through books with photographs of syndromes and malformations, pages and pages of well-studied textbooks and atlases, just to imprint the photos of classic syndromes onto her retinas. She is grateful for those photographs and feels indebted for the education they provide: she would never see people with these rare conditions otherwise. These photographs will help her recognize and diagnose those once in a life-time cases—encephalocraniocutaneous lipomatosis, Antley–Bixler syndrome, Cornelia DeLange in a blond newborn boy. Her brain works this way, it retains images and diagnoses stick to it like glue. The more obscure and esoteric the diagnosis, the better it sticks. She wants to become an expert diagnostician who recognizes the strangest constellations of findings and puts them together into a picture from puzzle pieces. She will hunt zebras—the rarest of the rare diseases. Her desire is to answer the “What is it?” question for her patients, to make the diagnosis. Only two photographs ever upset her—one in the seminal textbook on human malformation and the other in an excellent text on dysmorphology examination. The first one is a photograph of what appears to be a South-Asian-appearing boy with underdeveloped eyes: his eyelids fused, sparse eyelashes poking though where the palpebral fissures should be (by now she has learnt the terminology), and underdeveloped genitalia, he stands naked, feet apart. It is not just his nakedness that bothers her but he appears to be standing in a middle of an open courtyard of a colonial building, sun-filled, and bright. The boy looks almost as if he were scrunching his eyes against the glare that he cannot see. It is the setting—not a clinical office, not a photographer's studio where his nakedness might be acceptable, but a public place with people milling around just beyond the frame—that bothers her. How inappropriate. Doubly so: once for the photo to be taken in such a fashion, and secondly, for it to be included in this textbook. She will not see the second photo until she is pregnant and studying for her genetics fellowship exam. She has seen this condition in a real baby in a real NICU, in full color and tragic reality, but now she sticks PostIt™ notes over a black and white photo of a harlequin fetus, and secures them with paper clips so that they do not accidentally come off as she flips the pages when she is studying. It remains covered until well after her baby is born. The clinical geneticist revels in the intellectual challenge, the hunt for clues, the detective work, the feeling of accomplishment when all the pieces fit. It happens when she recognizes Angelman syndrome across the waiting room (she still thinks of “Angelman syndrome,” not “a girl with Angelman syndrome”), or when she diagnoses an infant with Miller–Dieker syndrome in a photograph shown in passing in the hospital corridor. Sometimes she can do it in her head, sometimes with the help of computer databases, textbooks, and atlases, but however she does it, it is always with a feeling of satisfaction. In her mind, she diagnoses strangers, too: the sales clerk at an airport duty-free shop with hypochondroplasia, the usher at a famed Italian theatre with metaphyseal dysplasia, the writer at a literary gathering who appears to have Marfan syndrome. She never approaches them, never says anything to them, but she does say something to the father of a newborn with an unexpected Down syndrome. He thanks her profusely a few months later, after the neurosurgeon removes his pituitary adenoma and saves his sight—she recognized the features of acromegaly. While still in training, the clinical geneticist-to-be starts a teaching slide collection. Photographs illustrating clinical findings, syndromes, pathology slides, X-rays. When an interesting patient is seen in the clinic her parents are asked without as much as a by-your-leave to go to the photography department with a yellow requisition on which a homunculus with its body parts circled shows what is to be photographed. She does not remember anybody ever refusing to go, no consents were obtained, either, the doctor ordered photos, photos were posed for, and taken. She wonders about the discomfort the parents and the patients may feel, but she does not question the status quo—she needs to belong, she does not want to appear weak or to rock the establishment's boat. Her professional future depends on the evaluations and reference letters. She will regret her compliance many years later. When digital photography emerges, photos of every known and unknown condition flood the internet, but she continues to take photographs of her patients. She is glad that the academic hospital where she works requires consents for all types of patients’ recordings. She documents both the clinical features of the known syndromes, as well as the unknowns that are shared with colleagues at conferences and meetings in the hope of arriving at a diagnosis. Maybe somebody has seen a patient with this constellation of findings in their practice. Maybe, it can be written up as a new syndrome. After a few years, however, she realizes that if she does not know what it is, not too many of her colleagues will know, either. A suggestion might be floated, but often it does not pan out on testing. So after a few years she stops taking photographs of patients altogether. Several times during her training she watches the attendings give bad news—a prenatal diagnosis of a lethal skeletal dysplasia, a diagnosis of Tay–Sachs disease in an eight-month-old girl, a positive result for Huntington disease. An erroneous prenatal that results in a birth of a second affected child. No matter how affected she is after those sessions, the subsequent discussions are never about anything other than the diagnoses—examination of one's own feelings is not indulged in. Patients come and go; those with diagnoses are the most satisfying, those without most frustrating, the ones with lethal conditions the saddest, but nobody talks to her about how she feels about those affected children, the life-shortening diagnoses, the terminations of pregnancy, and the malformed fetuses she has to examine. It is not supposed to bother her so she acts as if it does not. But it does. She passes her fellowship exam, she receives hospital and university appointments. No more training wheels, no more safety net. She diagnoses children with intellectual disability, with life-shortening conditions, and changes the lives of their families forever. An eleven-year-old girl with OTC deficiency dies in hyperammonemic coma while she is on call. She blames herself for years to come. But it is the prenatal diagnosis service where her job takes its heaviest toll on her. Those truly life-and-death decisions. She supports the parents no matter what their decision might be with non-judgmental, non-directive counseling. But who supports her? She copes the best she can, but in the end it is not enough and there are personal and professional consequences. With time the clinical geneticist realizes that there is a lot more to genetic diseases than the hunt for diagnosis, the identification of dysmorphic features, or the delineation of syndromes. There are patients and parents who need to talk, there are patients who will never be diagnosed, but who still need to be heard, who need emotional support in addition to medical support. She needs to listen, she needs to be there with all her capacities intact, caring, providing, supporting, thinking about them, and believing in them. They need her to care. Sometimes they come for their follow-up visits just to talk and to be heard: patients, parents, care-givers, grandparents. So she sits and just listens. But the clinical geneticist, too, needs to be heard, her feelings are just as important and as significant. If she does not take care of herself, she cannot take care of them. She starts to write, to share her stories, in order to make others realize that diagnosis is not the end-all and the be-all. She learns to sit and to listen, to let patients and parents sit and talk. She is the sounding board, the reverberating string to her patients’ emotions. She does not rush off to look things up in books or online—at least not immediately. She puts a mirror to their plight, she accompanies them on their journey. And she starts to ask for help for herself—from colleagues, from mentors, from her students. She continues to diagnose diseases and to counsel about inheritance patterns and recurrence risks—she does not stop being a clinical geneticist. She does not stop writing articles and presenting papers on the etiology or pathophysiology of genetics conditions. She remains dedicated, competent, and passionate, but she also takes care of her patients’ emotional needs and of her own mental health. As she writes literary fiction about genetic conditions, about the emotional aspects of the medical training and genetics practice, about the heartbreak and the tears she has shed inside without letting anyone know, she hopes that her stories will validate and vindicate her patients’ and their families’ and her own emotions. And she writes an article about the natural history of a clinical geneticist in the hopes of helping others understand that they cannot do it alone. I carried the seeds for this article for years, but they did not germinate until a dinner with John Carey in Salt Lake City in March 2015. I thank John for this and for the home he has given to narrative medicine and humanities in the Journal.

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