Medical Genetics residency education occurs in a variety of venues, but most would agree that the most important is the clinical encounter. Our patients remain our best teachers, a fact I remember every day in clinic or on rounds with our residents. This is especially magnified at the start of the academic year when almost everything is new, and the conversations can take so many different routes. We can focus on academic knowledge, which must be mastered to pass their ABMGG certification exam. For example, a recent discussion focused on how the common p.Gly380Arg variant in FGFR3 causes achondroplasia. We covered concepts like advanced paternal age, gain of function, mechanisms of excessive activation of FGFR3 signaling, and how that affects chondrocyte proliferation and maturation (Rousseau et al., 1994). From there, we went on to other molecularly related conditions, their complications, and appropriate management (Legare, 2022). These are fascinating discussions that I never tire of.

Sometimes, however, the discussion may take an entirely different, less academic, route. When we were consulted on an infant with poor growth and microcephaly, we discussed how much information can be gleaned from even the simplest of patient data, the child's growth parameters (Robin, 2016). Or conversations can be even more mundane, such as explaining the need to always directly communicate your thoughts and impressions by phone or (preferably) in-person to a member of the ward team who placed the in-patient consult. While less erudite these topics are every bit as important in the life of a medical geneticist, and therefore, in the education of a resident.

In the midst of another busy adult general genetics clinic, my clicking and scrolling were interrupted by a cell phone call. The call was from my colleague and friend, a neurosurgeon, which was quite unusual. He and I would typically text mid-week to plan our weekend golf. This was a Monday morning. Curious, I immediately picked up the call.

“What do you know about Cleido-crano dysplasia?,” he asked, hesitating as he drew out the name of the condition. “I am seeing a young woman who says she has this, and it seems to fit, from what I can tell. She has had a worsening headaches for the past few weeks, and now has a defect in her visual fields.”

“Jim, I am no neurosurgeon, but this sounds like an intracranial process going on. A tumor or maybe pseudotumor cerebri?”

“Thank you, doctor,” he responded in his typical sarcastic tone. “I concur. Scan supports pseudotumor. My question is what about this ‘Cleidocranial’ thing.”

I actually knew a fair amount about cleidocranial dysplasia (CCD). As a postdoc in Max Muenke's lab at the Children's Hospital of Philadelphia, I spent the better part of 8 months examining dozens of CCD patients and collecting blood for gene mapping studies (Feldman et al., 1995). We were scooped (Mundlos et al., 1995) (I have obviously gotten over it by now), but I knew the condition well first-hand. Hydrocephalus was not a classic feature of CCD, although I could imagine it occurring if the skull was somehow severely affected. But that would be typically in infancy, not as a young adult.

“I will look into this, but from what I know I do not think any intracranial processes are commonly seen in Cleidocranial dysplasia.”

I said I would get back to him. My friend thanked me.

After I confirmed that CCD was indeed the correct diagnosis—the young lady had been seen by one of my genetics colleagues 15 years earlier, and a RUNX2 pathogenic variant had been found. Then I did a thorough PubMed search, which confirmed the lack of any reported association of CCD with hydrocephalus.

Speaking with my friend again, I advised him to treat her as if she were an otherwise healthy young woman, which she really was. CCD had little effect on her life. He took my advice and began treating her for pseudotumor cerebri. Her headaches soon resolved, and her visual deficit was improving.

So why is this case important? Why did I discuss it at our weekly “coffee and cases” meeting with our residents? Simple; because it illustrates an important and often overlooked principle in the care of children and adults with a genetic syndrome, namely, just because a patient has a genetic syndrome does not mean that every issue is due to the genetic syndrome.

For people with these rare conditions (and remember, almost every genetic syndrome is “rare” to the nongeneticist), there is the temptation to ascribe every medical issue to the underlying genetic condition. “Occam's Razor” is emphasized to us at every stage of medical education, that one should seek a single diagnosis to explain all of your patient's findings. This often makes sense, but as we are learning in genetics, what makes sense may not always be what is in fact true. Some patients do indeed have more than one genetic diagnosis (Linscott et al., 2021), and some patients, like the young lady with CCD, have another medical process with their rare syndrome. In these instances, it is essential to recognize this, including to keep the treating physician from looking for another explanation, thereby delaying care. My colleague sees pseudotumor cerebri frequently and is perfectly comfortable treating it, but the underlying diagnosis of CCD threw him off. He was looking for another explanation for the patient's findings that would align with her rare genetic diagnosis. All he needed was some reassurance that he did not need to look any further down this particular path, and things were fine.

The notion that patients with syndromes can have one or more medical issues not related to their underlying syndrome is obvious, but it is often forgotten. The truth is those common things are common, even if the individual has an underlying condition that is anything but common. It would not be unusual for a child with achondroplasia to also have myopia, or an infant with poor growth and microcephaly to develop hypercholesterolemia as an adult…or for a young woman with CCD to develop pseudotumor cerebri. Of course, there should always be an investigation into a possible connection with the genetic syndrome, and it would be important to consider how the underlying diagnosis might affect care. For example, there would be management considerations regarding IV fluids in people with certain inborn errors of metabolism who are “NPO” prior to surgery. But if a literature review or other such follow-up fails to show such a link, it does not mean one should publish a case report entitled “Expanding the Phenotype of … .” The patient just has a common medical issue, like any person can get, and they should be treated for it like anyone else.