Digital clubbing

Abstract

Digital clubbing is an ancient and important clinical signs in medicine. Although clubbed fingers are mostly asymptomatic, it often predicts the presence of some dreaded underlying diseases. Its exact pathogenesis is not known, but platelet-derived growth factor and vascular endothelial growth factor are recently incriminated in its causation. The association of digital clubbing with various disease processes and its clinical implications are discussed in this review.

Inactivating Mutation in the Prostaglandin Transporter Gene, SLCO2A1, Associated with Familial Digital Clubbing, Colon Neoplasia, and NSAID Resistance

“…These included 1 frame-shift, 52 missense, and 1 nonsense mutation that mapped to the coding regions of 52 genes. Given prior studies, we first focused on variants mapping to genes involved in prostanoid synthesis or degradation pathways (1–14). The only such mutant gene was SLCO2A1 that encodes the principal prostaglandin transporter and is involved in the uptake of PGE 2 for degradation (40, 41) in which a nonsense mutation (p.G104X, codon 104) was segregating in family 1867 (Figures 1 and 3).…”

“…Digital clubbing is characterized by focal bulbous enlargement of the terminal segments of fingers and/or toes, and in sporadic form is associated with a variety of clinical conditions including cancer, cardiovascular disease and inflammatory disorders (1). Familial digital clubbing is a rare inherited genetic disorder that shows an autosomal recessive or a dominant inheritance pattern with variable penetrance, and may occur as part of the syndrome of primary hypertrophic osteoarthropathy (PHO) characterized by periostosis, pachydermia, and digital clubbing (1).…”

“…Familial digital clubbing is a rare inherited genetic disorder that shows an autosomal recessive or a dominant inheritance pattern with variable penetrance, and may occur as part of the syndrome of primary hypertrophic osteoarthropathy (PHO) characterized by periostosis, pachydermia, and digital clubbing (1). In the familial form, a significant gender bias has been noted where affected males predominate (7:1 male: female ratio) (2, 3).…”

“…In the familial form, a significant gender bias has been noted where affected males predominate (7:1 male: female ratio) (2, 3). Inherited genetic defects in components of the prostaglandin degradation pathway have been associated with familial PHO/digital clubbing in diverse patient populations from around the world (1–14). These include homozygous loss-of-function mutations in the HPGD gene encoding the prostaglandin degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) (4–8, 13), and both heterozygous and homozygous inactivating mutations in the solute carrier organic anion transporter family, member 2A1 ( SLCO2A1 ) gene that encodes the principal prostaglandin transporter (PGT) that mediates prostaglandin uptake into the cell and hence provides substrate for degradation by 15-PGDH (9–12, 14–19).…”

A skeletal case of hypertrophic osteoarthropathy from the Canary Islands dating from 1000 BP

“…It is usually associated to digital clubbing (Benedek, 1993;Gibb et al, 2013), but it is still discussed whether HOA and digital clubbing are the same entity in different evolutive stages (Pineda et al, 1985), or different diseases (Sarkar et al, 2012). Chronic hypoxemia leads to increased levels of platelet-derived growth factor (PDGF) and vascular-endothelial growth factor (VEGF; Silveira et al, 2000), which can also be autonomously secreted by neoplastic tissue (as angiogenic factors).…”