Dupuytren’s disease (DD) is a nodular palmar fibromatosis of unknown cause. The disease process leads to shortening of the palmar fascia and permanent contractures of the digits. DD is an irreversible, progressive disorder with a high rate of recurrence after surgical excision. DD is a familial condition, which is extremely common in individuals of Northern European extraction. DD is considered to be one of the most common heritable disorders of connective tissue in Caucasians.
The genetic literature on this disorder is very sparse and the mode of transmission is uncertain. Various patterns of inheritance have been proposed as the likely mode of transmission although no single gene has so far been identified.
Various risk factors such as age, sex, smoking, diabetes, anticonvulsant medication, alcohol abuse, cirrhosis of the liver and manual labour have also been implicated in DD pathology. However, the relevance of some of these aetiologic factors in DD pathology have been questioned and none so far has been proven to be of significant value in understanding the pathology. There are however, two elements in the aetiology of DD that clearly stand out. One is the common occurrence of this condition in Caucasians and the other is the familial nature of the disease.
Successive cases of DD (n=255) were entered into the study. The age range was between 37 to 90 years with a mean age of 56.9 years. Cases were all Caucasians from the Northwest region of England; U.K. All cases were seen by the first author who took a full medical history using a proforma and examined both hands and feet of each individual case. All cases had confirmed diagnosis of DD with the presence of characteristic Dupuytren’s nodules in the palm of the hand and/or digits with or without contracture of either the metacarpophalangeal joint (MCPJ) or the proximalphalangeal joint (PIPJ).
The following information were noted in detail at interview: Profession, hobbies, hand dominance, family history, past medical history, medication, alcohol intake, date of onset of disease, history of trauma, symptoms, treatment, result and recurrence. One hundred and ten cases (43%) had a positive family history. There were 38 cases who had 2 sib pairs with a diagnosis of DD and 10 cases who had more than 3 sib pairs with DD. Interestingly from the those DD cases with a positive family history 14 had plantar nodules, 2 had plantar nodules with Peyronies disease, and 6 had familial knuckle pads. There was one case of DD with a strong family history that had simultaneous “diathesis” of plantar nodules, Peyronies and knuckle pads.
We identified a number of different inheritance patterns (dominant, recessive and maternal transmission) in our familial cases. In view of the variable patterns of transmission and the sporadic nature of the disorder; we propose that DD is a complex oligogenic condition involving a number of genes as opposed to a simple monogenic Mendelian disorder.
The detailed genetic basis of DD is key to understanding its pathogenesis and providing future prognostic and diagnostic advice to patients and to developing novel therapeutic regimes for its treatment.