Scientists have identified a mutation in a gene that causes digital clubbing, a deformity of the fingers and fingernails that is associated with a number of diseases of the heart and lungs. The finding, published online this week in Nature Genetics, may have immediate implications for the diagnosis of a range of disorders that are associated with clubbing.
Sometimes called ‘Hippocratic fingers’?Hippocrates may have been the first to propose clubbing as a sign of disease?bulbous or club-shaped fingers are one of the first clinical features that medical students are taught to look for in conducting an examination. It is almost always the sign of serious disease, notably lung cancer, heart disease, hyperthyroidism, and disorders of the gastrointestinal tract.
David Bonthron and colleagues studied three Pakistani families with primary hypertrophic osteoarthropathy (PHO), a disorder in which clubbing is accompanied by painful joint enlargement. They mapped a mutation in the gene encoding 15-hydroxyprostaglandin dehydrogenase, which is the main enzyme responsible for the degradation of prostaglandins ?fatty compounds. They went on to show that the individuals with PHO had chronically elevated levels of one particular prostaglandin called E2. The known functions of prostaglandins provide a plausible explanation for the clinical features of PHO, and suggest that other disorders where clubbing is secondary to lung cancer or heart disease may also be explained by consistent exposure to elevated levels of circulating prostaglandins.
The authors suggest that a straightforward urine test for levels of prostaglandin E2 may be a useful first step in the diagnosis of individuals with unexplained clubbing.