This is another archival repost from the old blog, originally from oct 2007.
It’s not healthy to bottle up your worries and stress. That’s why all the best comedy throughout the ages has dealt with the tough issues that worry us. It’s why doctors make jokes about diseases and pathologists laugh at unpleasant deaths. Its why the “Darwin Awards” are such a successful concept. We have a collective fascination with death and disease: what happens when our bodies and minds go wrong tells us things about what we are. I am therefore initiating a “Sunday syndrome” column for the discussion of developmental abnormalities that tell us interesting things about ourselves and our world. For this first post, I’ll introduce a serious of ides which I’ll discuss in depth in later posts; and in each post I will introduce a new example syndrome. As this introduction suggests, the posts will at times be light-hearted, and using a Peter Griffin quote as a headline is not meant to insensitive.
Our first syndrome is Prader-Willi Syndrome (OMIM:#176270), and the first question we need to ask is: “what is a syndrome?” A syndrome is merely an association of several symptoms — that is, abnormal states — occurring in multiple individuals. In Prader-Willi, the main symptoms are mild mental retardation (if the politically incorrect choice of words grabbed your attention, there will be more about those in a later post) and a difficulty controlling eating, leading to obesity. It is tempting to use the word “syndrome” as a synonym for “disease”, but disease implies impairment and distress (literally, lack of ease), which though common, are not necessary conditions of “syndrome”. Some symptoms may be hard to objectively categorise: one man’s “impairment” may be another man’s “healthy variation in human aptitudes.” Generally, a disease will have the same or similar causes and development (aetiologies) in all individuals, which is not always the case for syndromes. The syndromes we will be looking at are all caused by genetic aberrations, leading to developmental abnormalities; but often, one syndrome can be caused by any of several genetic aberrations, and this will be the subject of a later post. Perhaps our best objective measure of what is “disease” is to look at its effect on life expectancy, and using this measure, we will include many of our syndromes. “Syndrome” and “disease” therefore overlap, but are not synonyms. Another concept intimately linked to “disease” is the pursuit of a “cure”. This obviously can not apply to abnormalities of development, but it is, to varying extents, appropriate to talk of “intervention” and “treatment”, as I will discuss in a later post.
Prader-Willi has a frequency of around one in 25,000-30,000 live births.[1][2] It’s not easy to visualise what large numbers like these really mean, but we can predict, for example, that around 25 people will be born with Prader-Willi in the UK each year — a much more manageable number for the imagination.[3] Prader-Willi is caused by the deletion of a small section of one of the two copies of chromosome 15 (in the twelfth section of the long arm, to be precise), resulting in the loss of a handful of genes — typically seven. Deletions are one of several errors that may occur during the production of gametes (sperm and eggs), and these syndromes therefore help us understand the molecular details of sexual reproduction and evolution (the topics of later posts). Prader -Willi has both physical symptoms — short stature; poor muscle tone at birth; small hands and feet; and distinctive facial characteristics — and mental symptoms, resulting from abnormal brain development — low IQ (most individuals in the 40-80 range[4]), but with good visual processing, reading and vocabulary; and extreme, insatiable appetite. Such seemingly random combinations of physical and mental symptoms are common in syndromes resulting from the deletion of small numbers of genes. This phenomenon indicates the complexity of developmental programmes, and the problem with the simplistic picture of genes as being “for” a particular phenotype. This complexity of development also hints at the problems with the “nature vs nurture” dichotomy, which still haunts discussions of genetics and development; and the clear effect of genetics on mental aptitude in abnormal states, brings up the tough question of the general effects of genetics on mental aptitude in the general population. These topics will be the subjects of the next two editions of this column.
References
- ^ J E Whittingtona, A J Hollanda, T Webbb, J Butlera, D Clarkec, H Boer, 2001. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 38:792-798 Full Text
- ^ A Smith, J Egan, G Ridley, E Haan, P Montgomery, K Williams, E Elliott, 2003. Birth prevalence of Prader-Willi syndrome in Australia. Archives of Disease in Childhood 88:263-264. Full Text.
- ^ A quick and dirty estimate based on the registration of births in England and Wales (PDF).
- ^ Cassidy S.B. 1997. Prader Willi Syndrome. Journal of Medical Genetics 34:917-23.