The Dorland’s Illustrated Medical Dictionary (2012) variously defines a syndrome as:
• a set of symptoms that occur together;
the sum of signs of any morbid state
• a symptom complex
• a pattern of multiple malformations thought to be pathogenetically related
Like Potter Stewart*, we may not agree on the definition of a syndrome, but we know one when we see one.
*Potter Stewart (1915-1985) was a US Supreme Court Justice who famously said of pornography in Jacobellis v Ohio (1964), I can’t define it, but I know it when I see it
As a medical lexicographer, I’ll add another definition.
• a symptom complex that affects two or more tissues or organ systems. This definition addresses the phraseology that has appeared in the literature, e.g., non-syndromic deafness, non-syndromic cleft lip/palate, non-syndromic mental retardation, which affect only one “system” such as the auditory apparatus in deafness or the neuropsychiatric axis in mental retardation. Unfortunately, not every disorder that has been called a syndrome is a syndrome–e.g., organic brain syndrome–is caused by cortical atrophy, the primary pathology resulting in a constellation of psychiatric sequelae, which are secondary phenomena. Contrariwise, not every condition that hasn’t been labelled as a syndrome isn’t a syndrome–e.g., citrullinemia.
Ignoring for the moment the semantics of what is and what isn’t a syndrome, the term has become increasingly popular. The 1932 edition of the Dorland’s* listed 160 syndromes in its estimated 80,000 entries or, to make the math easier, 1 in 500 entries (± 0.2%) in the 1932 Dorland’s was a syndrome. The 2012 edition lists 1435 syndromes in its 125,000 entries, or 1 in 90 (> 1%) terms in the current Dorland’s is a syndrome, for a nearly 6-fold increase in 80 years. The Modern Medical Dictionary (MMD) database, which informs this website, has 5800 syndromes listed in 190,000 entries, or 1 in 30.
*At the time, it was still called the American Illustrated Medical Dictionary; the 160 syndromes listed included aliases
When a syndrome is first described, typically by the authors for whom the syndrome is usually named, the description focuses on aset of symptoms which become the entity’s defining characteristics. List the symptoms, so goes* the thinking, and diagnosing the disease should be pretty straightforward. Enter the Human Genome Project: some syndromes are caused by two or more different genes–e.g., Cole-Carpenter syndrome, an osteogenesis imperfecta-like disorder. Cole-Carpenter syndrome 1 is an autosomal dominant condition (OMIM catalog number 112240) caused by a defect of P4HB, which encodes a multifunction intracellular enzyme. Carpenter syndrome 2 is an autosomal recessive condition (OMIM catalog number 616294) caused by a defect of SEC24D, which encodes a coat protein complex component involved in vesicle budding from the endoplasmic reticulum and cargo selection.*went
As physicians, it is imperative that we recognize the limitations of the clinical diagnosis paradigm. Genetic manipulation–e.g., with antisense oligonucleotides, of SEC24D, the gene responsible for Cole-Carpenter syndrome 2 will do nothing if the patient has Cole-Carpenter syndrome 1. Many syndromes have three or more defective genes: Cowden syndrome has seven; Meckel syndrome has 12, Joubert syndrome has 23. I’m unaware of an App or subdatabase that summarizes these syndromes. We at MMD are developing a tool intended to address that gap, by offering summarized information on syndromes and the affected genes, beta versions of which should be available by the end of this (2017) year.
Finally, a modern medical dictionary must choose whether to ignore or include “syndromes” created by a blogger, screenwriter or other creative author with a keyboard, computer and access to the internet. Most of these entities–e.g., Father Mulcahy syndrome, I love you syndrome, red truck syndrome, and scores of others created to fill lexical voids, are not, and never will be regarded as syndromes in the medical sense. Others–e.g., short man syndrome, may have enough mental-health-related features to warrant incorporation in a medical dictionary.
I believe that a medical lexicon serving the needs of physicians and health professionals in the 21st century is duty-bound to include any term labelled “syndrome”, indicating its level of legitimacy. At this point, the MMD database has less than one hundred non-syndrome “syndromes”, which will be included in the App currently under development and slated for release as a beta in mid 2018. Stay tuned.