deletions in the q arm of chromosome 1 at position 36, [60-70% of cases]) that lead to lose of TNFAIP3 (encodes tumor necrosis factor, alpha-induced protein 3 which inhibits the activation of NF-κB, blocks cell death due to apoptosis, and regulates lymphocyte-based immune responses through its ubiquitin ligase activity); 3) mutations in PRDM1 (encodes the PR domain zinc finger protein which promotes the maturation and proliferation of B-cells); and 4) the same mutations seen in ISFL including KMT2D (85-90% of cases), CREEBP (40-65% of cases), BCL2 (40-65% of cases), and EZH2 (20-30% of cases) as well as other mutations such as those in the histone-modifying gene HIST1H1E (20-30% of cases), the RRAGC gene (~17% of cases) which regulates cell growth, survival, death, and proliferation, and, in ≤15% of cases several other genes including MEF2B, STAT6, EP300, ARID1A, SLC22A2, CARD11, FOXO1, GNA12, B2M (i.e. the gene for beta-2 microglobulin), and SGK1. Except for the t(14:18)(q32:q21.3) translocation and EZH2 mutations which lead to gains in the expression and function, respectively, of their products, the genetic alterations generally lead to a loss in the production or function of the cited genes products. However, the exact roles, if any, of these genomic abnormalities in promoting the progression of ISFL to FL are unclear.
Risk factors
Identified risk factors for plantar fasciitis include excessive running, standing on hard surfaces for prolonged periods, high arches of the feet, the presence of a leg length inequality, and flat feet. The tendency of flat feet to excessively roll inward during walking or running makes them more susceptible to plantar fasciitis. Obesity is seen in 70% of individuals who present with plantar fasciitis and is an independent risk factor.Plantar fasciitis is commonly a result of some biomechanical imbalance that causes an increased amount of tension placed along the plantar fascia.Studies consistently find a strong association between increased body mass index and plantar fasciitis in the non-athletic population. This association between weight and plantar fasciitis is not present in the athletic population. Achilles tendon tightness and inappropriate footwear have also been identified as significant risk factors. Pathophysiology
The cause of plantar fasciitis is poorly understood and appears to have several contributing factors. The plantar fascia is a thick fibrous band of connective tissue that originates from the medial tubercle and anterior aspect of the heel bone. From there, the fascia extends along the sole of the foot before inserting at the base of the toes and supports the arch of the foot.Plantar fasciitis is a non-inflammatory condition of the plantar fascia.