The Half Decent Pharmaceutical Chemistry Blog

I’ve meant to write this post since the day I started to work at my graduation thesis, but I have to say my professor, not my supervisor, wondered whether to change my project or not: because of a lack of working-force, he was tempted to concentrate all our strengths (meaning people) on a single project, with the ambitious target of eventually producing an article out of it as soon as possible. However, my supervisor and I have recently solved this problem by making me work on both projects.

So, what am I having to do with these days? Cockayne Syndrome. However, this being meant to be a molecular biology project, I am not spending too much time on the pathology itself, but I only care at the molecular details. Still, a brief presentation of this terrible, rare disease could be fruitful for my thesis, given that the odds are that nearly all the people reading it will be pathologists, pharmacologists and pharmaceutical chemists.

Let’s kick off with an eerie picture of the ultimate, phenotypic manifestations.

As I said, this is a very rare disease. So rare I hadn’t heard of it until my supervisor presented the project and even she did a very short introduction talking about some basic features of this syndrome. And you know how much I like unusual, bizarre diseases, don’t you?
Cockayne syndrome (usually abbreviated CS) is an autosomal, recessive disorder. After almost three months reading papers where no author showed any attempt at coming up with an alternative definition, but, instead, preferred to stick to this formula, I annoyingly know it by heart. Still, although I am fed up with it, I must admit it says a lot about CS.

Unsurprisingly, such an uncommon illness was named after the person, in this case a British physician, who discovered or, at least, studied it most comprehensively. Edward Alfred Cockayne wrote an article where he described a multi-system disorder which bore some resemblance to dwarfism, although, from a molecular point of view, it has more in common with Xeroderma Pigmentosum, with impaired DNA repair and UV hypersensitivity being common characteristic of both pathologies. Unlike Xeroderma Pigmentosum, though, CS patients don’t show an unusually high rate of skin cancer.
As the picture shows, CS has dramatic and evident phenotypic consequences such as the abovementioned dwarfism and photosensitivity, premature aging, microcephaly, facial abnormalities (beaked nose, for instance), retinal atrophy, catastrophic teeth fragility, impaired movements (similar to those sometimes experienced by elderly people) and tremors.
But there’s more: neurological abnormalities and mental retardation are as severe as these outlined physical, exterior signs.

Generally, these symptoms start to appear in the first two years of life, as the foetus grows normally, and life expectancy varies between 10 and 20 years. A second, even rarer form of Cockayne syndrome, however, is hallmarked by immediate onset, which leads to abnormalities detectable at birth and, predictably, life expectancy doesn’t exceed 10 years.

Stay tuned for the molecular, sordid details of how DNA repair is badly altered in CS cells.