My journey with Gorlin Syndrome (part 1)

I met Dr Georgia Chevenix- Trench, in the 1990s, when she came to Adelaide. In collaboration with research groups around the world, the research group at the Queensland Institute of Medical Research was hoping to find and study "the gene for Gorlin Syndrome". An initial step in this kind of research involved taking samples from people with GS and from their close relatives, and comparing their chromosomes, to discover which chromosome was physically altered to cause GS. Georgia examined me and took blood, confirming that I do indeed have GS, but she told me that nobody would use my case to represent GS in a medical text book, as I was so mildly affected. She examined my parents, and took blood from them as well. In those days, they occasionally mailed a "BCNS Newsletter" to update the participants, and Georgia also contacted me a few more times, after our meeting. Georgia asked me to write something about the effects of GS on my life, as they were relatively mild; she hoped it would encourage those who were frightened by the medical literature, which generally emphasise the severe effects of GS. She mentioned how worried they were about a certain 18yo girl who had become depressed on learning she had GS. I wrote my article, and Georgia said it had helped the girl, and she also published it in the "BCNS Newsletter".

I just found the issue in which my story appeared, in February 1994. It was in my shed, in a folder full of the medical papers I copied and read soon after diagnosis; as a scientist, it was how I coped at the time. I felt that knowledge was power, and it enabled me to think of ways to keep the impact of GS on my life as mild as possible. Later, for several years, I seldom thought of GS: I just took care of my skin, and had checkups and excisions when necessary, but in between I tried to "think normal". There are other issues in life, after all.

I will tell my recent story at another time, but note a few updates for now:

I wrote this article in 1994; since then, Dad had his third melanoma; a “Hutchinson's Freckle”; it came back, years after excision, and killed him in 2007 at 90 years. Mum died at 89 years, in 2010. She was always well, until she developed bowel cancer at 86 years (newly widowed) then myeloma at 87 years; that killed her.

I now call GS“ Gorlin syndrome” ; omitting the “'s”.

My BCC tally is now around 75, counting those that were excised and tested. I have used Aldara cream many times, seeing hundreds of spots reacting, most of which were probably tiny (“sub –clinical”) BCCs; the early stage is called “naevoid” --- or“nevoid”, in American spelling.

Age 56 now, new oral cysts are unlikely, but others in the Adelaide group have had oral cysts in midlife, so I should organise a check for that, one of these days. Kristi Schmitt Burr, Executive Director BCCNS Life Support Network, recently wrote to me: “World Health Organization determined that our oral cysts should be called Keratocystic Odontogenic Tumors (KCOT or KOT) and that oral cysts is too wide an identifier. If we are educating our members about the presence of these invasive growths, and the nature of their rapid advancement, I suggest using the new global term.” The people I met who had “incomplete dentition” (missing teeth) did not have GS; this sign can occur in other situations.

Dad's brother is still alive, and doing OK for a man in his late eighties.

Once the PTCH1 gene was found, its function was soon understood, as similar genes had been extensively studied in Drosophila fruit flies and in mice.

Georgia told me that about 30% of GS people in her lists are "new mutants" and she commented that is a high % for a condition that does not prevent people having children. I never wanted to have kids, so all is well; my little deletion ends with me. BTW, she let me know that mine was small, as that fact had saved them a huge amount of work, in locating the gene "for" GS, back then. Great timing! I had only realised that I had GS a few days before Georgia was due in Adelaide, on that last trawl for blood etc before the big "push" to track down the DNA sequence. I am a scientist, so I was thrilled that my appearance on the GS scene (so to speak) saved them a lot of lab work; that GS gene had to be somewhere in the small bit of DNA missing in one of my chromosome, and they found what was necessary.

Being a carer for my elderly parents, plus working, plus my chronic fatigue + pain (fibromyalgia) kept me ..... busy / stressed / stretched, in recent years. Now, I have time to take care of myself.

From "BCNS Newsletter" February 1994:

In June 1993, at the age of 39, I discovered that I have Gorlin's syndrome. I had wondered why I had undergone so many operations, especially that I had already had 11 basal cell carcinomas removed. The doctors had been nagging me about staying out of the sun, apparently assuming that I had incurred the cancers by excessive sun - worship usual among Australians, but I have very fair skin, begin to feel the "bite" in ten minutes, and after several sun burns in childhood, I have tried to avoid the full force of the sun. I knew that sunshine caused wrinkles and cancer by observing the older generation. My father has spent a lot of time in the sun and has had all three types of skin cancer - two melanomas and uncounted BCCs and SCCs - and my mother has had a few SCCs. This is not unusual for such blue - eyed, fair - skinned people after 70 - odd years enjoying farming, fishing and bowls in our climate. I burn much more quickly than they, so my participation in outdoor activities was limited and painful in the years before effective sunscreens. If I had known about Gorlin's syndrome then I would have been even more sun - conscious!

There were other signs that I had Gorlin's syndrome but no one thought anything of it. As a kid I thought my big head showed extra brains, to pick a silly example! The first real problems manifested in my 20s as four operations for keratocysts in the maxilla (upper jaw). A few teeth had failed to develop anyhow, and I lost more in the operations to remove the cysts. Recurrence of cysts within a year of the previous operation was particularly hard to take, as I assumed the operations and tooth loss would go on forever, but the last cysts were removed 14 years ago.

During my Science degree, I had read a lot about Genetics, and tried to deduce what genes were in my family tree, as of course all families have some odd genes. I had often wondered if the cysts and missing teeth were associated with an underlying developmental error, and was fascinated to learn that some of my relatives had the same teeth missing. While working in '81 / '82 (on bacterial genetics) in the Genetics department at Monash University, I found a book on Human Genetics and, looking up "keratocysts", found a reference to Basal Cell Naevus Syndrome. I did not understand the jargon, and all I recall is that it was inherited (as a dominant gene so would be evident in carriers) and caused cancers and other terrible sounding disorders. I thought that all cases had affected relatives and all of the symptoms, and so concluded that I did not have BCNS. I did not ask advice. Since then, when occasionally I searched for references to keratocysts (to see what the risk of recurrence is after 10 - 15 years) I always rejected the papers that mentioned BCNS, being so sure that they had no relevance to my situation.

Dad's brother had a melanoma successfully removed 40 - 50 years ago and Dad had his first melanoma in 1982, so I began to have check - ups for skin cancer in 1983, but the dermatologist found nothing significant. The numerous little lumps in my skin, and the few suspicious moles he removed, were benign. This lulled me into a false sense of security, until a little lump on my nose began to expand more and more rapidly (my first BCC). I left it a little longer than I should because I could not believe that it was malignant. The repair work went well, and although I have had two other BCCs on my face, other people find it hard to trace the scars. Unfortunately, I have scarred more on my back.

While working at the Adelaide Children's Hospital last year, I had an informal chat to a dermatologist about my tendency to develop BCCs and she surprised me by looking at the palms of my hands and correctly guessing a bit of my medical history. I inferred from her line of questions that she suspected an inherited cause of these conditions, that it was rare and interesting, because she asked me if some of her colleagues could look at me. It was weird, being "Exhibit A", while three doctors talked at once, debating the diagnosis. Apparently they were not sure someone so mildly affected could have so - and - so's syndrome (I couldn't catch the name). None of us had time that day to sort out the situation. We were all supposed to be elsewhere doing our work! As a scientist, I was curious, and I was excited to think that there was a coherent explanation for so many coincidental ailments.

A couple of days later I looked up hereditary causes of basal cell carcinomas in the hospital library and was shocked to realise I had BCNS - the doctors had called it "Gorlin's Syndrome". The pictures in the textbooks frightened me. The prognosis seemed gloomy. I felt a terrible tension, not knowing if it was true or not. Two days later, by coincidence, I was able to meet Georgia Trench on a visit to Adelaide, and she gave me the first BCNS Newsletter and a lot of information which settled the matter for me. It was a relief to have my self - diagnosis confirmed so soon because the uncertainty was very wearing. A few months later it was confirmed in an official consultation in the hospital Genetics Department.

It was interesting to learn so much about the condition, for example that many cases have no affected relatives. One important aspect is the unpredictability of the effect of this gene in a person. I am so mildly affected that my condition was unnoticed by oral surgeons in Adelaide, Sydney and Melbourne whom I had consulted about keratocysts, by my dermatologist and plastic surgeon, and by all the other medical staff who have seen me. The medical literature emphasises the most severely affected cases, and this needs to change. For one thing, if the textbooks accurately reflected the wide range of effects of this gene in various people, doctors may correctly diagnose Gorlin's syndrome early in life so we can be given regular check - ups for tumours and could make appropriate choices of occupation and sports to minimise sun exposure. The texts that I found presented the extreme situation as typical, along with pictures of untreated cancers. First I felt the road went down, down all the way, then I remembered they are pictures of other people, not me, and I would not suffer like that if I continue my strategy of regular skin checks, begun years before hearing of Gorlin's syndrome. I stopped feeling sorry for myself as I realised how much worse it could have been. I also stopped feeling guilty, as this is not my fault. I now plan to educate my doctors about my underlying condition, and it is vital that they address my health needs sensibly. For example, my plastic surgeon had become irritable about my recurrent tumours, but has an improved attitude now he knows that BCNS, not sunbaking, is the problem.

Well, I am glad to know the truth, and to hear about others coping with this condition. That is why I wrote. I found the newsletter that Georgia gave me encouraging, and I hope my story will encourage others. At first I thought about BCNS a lot, but then I just got on with life, as before, finding work to do and focussing on more important things. Since 1975, when I decided to serve Jesus Christ in any way I could, I began to consider eternity more than the present, and my quality of life has been determined more by my spiritual health than by my bodily health. I am sure that none of my relatives have Gorlin's syndrome, which is good news personally, but from the research angle, I know it is important to follow this gene within families to learn more about what the normal gene does. That is, I assume the genetic material responsible for the trouble must be a defective version of a proper gene, unable to do its proper job on cellular metabolism correctly. What job would it normally do? One of these days I plan to check the literature for the answer, just for interest.