“When You Hear Hoof Beats, Think… Zebras”:
PCD and the Challenge of Rare Disease Diagnosis

By Michele Manion

"If you hear hoof beats, think horses—not zebras" is an adage popular in medical schools.  This phrase sums up the philosophy that it is generally more productive to look for common rather than exotic causes for disease.  However, for the more than 25 million Americans who suffer from an "orphan" disorder (affecting fewer than 200,000 people) just getting a diagnosis can be a heroic undertaking.  In a system designed for horses, being a zebra can be lonely, confusing, and frustrating.  This is the story of one little zebra. 

Meghan was born in 1983, the picture of infantile perfection (at least as far as her family was concerned) and at first we were so busy making observations about the miracle of genetics as presented in this perfect little package that we didn’t notice anything was wrong.  There were some problems, however.  Meghan had a minor pectus deformity and she seemed to have difficulty managing her secretions.  She had several episodes of choking and gagging while we were still in the hospital.  We were a little concerned, but were assured this was “normal” and we confidently took our new daughter home.

It didn’t take long for the uglier side of genetics to rear its head.  At three weeks of age Meghan had her first, of many, pneumonias.  She had 12 chest x-rays the first year of her life and was chronically sick with upper and lower respiratory infections and ear problems.  We were frantic to improve her health and took her to specialist after specialist, all of whom suggested different diagnoses to explain her symptoms ranging from her being a “juicy kid,” to atypical cystic fibrosis, refractory asthma and right middle lobe syndrome.  It was a frustrating situation for us and for her physicians, because when she was not sick, she seemed so extraordinarily healthy.  We started to investigate environmental causes, tried different climates and had her tested for allergies.  Nothing seemed to help. Finally we took her to a major clinic in our area famous for their diagnostic capabilities.  After two days of testing, we were told that her chronic lung infections were most likely the result of “improper nose-blowing technique.”  We were at the end of our rope.

Things got worse when school started.  Meghan was a social creature and loved activities.  She hated missing school, but routinely missed 10 to 20 days each quarter.  We were concerned about her academically, but what was even more distressing was watching her become discouraged about her health.  At one point she stated that  if there was nothing the doctors could do for her she would probably just die because it hurt so bad to breath.  She was six-years-old.  We pushed for answers yet again, and started the cycle of specialists all over.  Finally, when she was seven-years-old we found an infectious diseases doctor willing to work with us until we had some answers.  After three months of testing, he suggested a biopsy for ciliary dyskinesia.  By this time, Meghan had evidence of bronchiectasis in her right middle lobe and she had severe scarring of her tympanic membrane with some hearing loss.  Ciliary dysfunction seemed to explain her symptoms, so we went ahead with the biopsy.  Just before her eighth birthday, we got the results.  Meghan had primary ciliary dyskinesia (PCD).  She was immediately started on an aggressive regimen of airway clearance therapy and antibiotic treatment which managed to control the spread of her bronchiectasis. She still gets sick frequently, but is able to pursue a full life with work, friends and college.  Best of all, she has fulfilled her lifelong dream of working with horses.

People have asked me why it is important to know the actual diagnosis if there is no cure and no specific treatment.  Besides the obvious—PCD is a genetic disorder and it is important to know your family history—there is a huge emotional and mental benefit to families in knowing precisely what they’re dealing with.  The stress of trying to manage an unnamed, undiagnosed problem can be enormous.  From a practical standpoint, insurance coverage is more and more predicated on diagnostic code and knowing what you’re treating can make the difference between access to necessary services and denial of coverage.

So the next time you hear hoof beats, please remember that there are 25 million zebras out there.  You may just have encountered one.