Apart from TGFβ, connective tissue growth factor (CTGF) has a possible role. Indeed, a common CTGF gene polymorphism is present at an increased level in systemic sclerosis.Damage to endothelium is an early abnormality in the development of scleroderma, and this, too, seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion, and a type II hypersensitivity reaction  similarly have been implicated. Increased endothelin and decreased vasodilation have been documented.Jimenez and Derk describe three theories about the development of scleroderma:

The abnormalities are primarily due to a physical agent, and all other changes are secondary or reactive to this direct insult. The initial event is fetomaternal cell transfer causing microchimerism, with a second summative cause (e.g. environmental) leading to the actual development of the disease. Physical causes lead to phenotypic alterations in susceptible cells (e.g. due to genetic makeup), which then effectuate DNA changes that alter the cells behavior. Diagnosis
In 1980, the American College of Rheumatology agreed on diagnostic criteria for scleroderma.Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anticentromere and anti-scl70/antitopoisomerase antibodies), and occasionally by biopsy. Of the antibodies, 90% have a detectable antinuclear antibody. Anticentromere antibody is more common in the limited form (80–90%) than in the diffuse form (10%), and anti-scl70 is more common in the diffuse form (30–40%) and in African-American patients (who are more susceptible to the systemic form).Other conditions may mimic systemic sclerosis by causing hardening of the skin.
Léri–Weill dyschondrosteosis or LWD is a rare pseudoautosomal dominant genetic disorder which results in dwarfism with short forearms and legs (mesomelic dwarfism) and a bayonet-like deformity of the forearms (Madelungs deformity). Causes
It is caused by mutations in the short-stature homeobox gene found in the pseudoautosomal region PAR1 of the X and Y chromosomes, at band Xp22.33 or Yp11.32.SHOX gene deletions have been identified as the major cause of Leri–Weill syndrome.Leri–Weill dyschondrosteosis is characterized by mesomelic short stature, with bowing of the radius more so than the ulna in the forearms and bowing of the tibia while sparing the fibula. Diagnosis
Diagnosis is made following genetic blood testing. Treatment
History
LWD was first described in 1929 by André Léri and Jean A. Weill. References


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