In 20 patients (12 and 8 probands, respectively), missense mutations (R672H; MIM *160270.0001 and R672C; MIM *160270.0002) caused substitution of arg672, an embryonic myosin residue retained post-embryonically. Of the remaining 6 patients in whom they found mutations, 3 had missense private de novo (E498G; MIM *160270.0006 and Y583S) or familial mutations (V825D; MIM *160270.0004); 3 other patients with sporadic expression had de novo mutations (T178I; MIM *160270.0003), which was also found in DA2B; 2 patients had no recognized mutations. Diagnosis
Freeman–Sheldon syndrome is a type of distal arthrogryposis, related to distal arthrogryposis type 1 (DA1). In 1996, more strict criteria for the diagnosis of Freeman–Sheldon syndrome were drawn up, assigning Freeman–Sheldon syndrome as distal arthrogryposis type 2A (DA2A).On the whole, DA1 is the least severe; DA2B is more severe with additional features that respond less favourably to therapy. DA2A (Freeman–Sheldon syndrome) is the most severe of the three, with more abnormalities and greater resistance to therapy.Freeman–Sheldon syndrome has been described as a type of congenital myopathy.In March 2006, Stevenson et al. published strict diagnostic criteria for distal arthrogryposis type 2A (DA2A) or Freeman–Sheldon syndrome. These included two or more features of distal arthrogryposis: microstomia, whistling-face, nasolabial creases, and H-shaped chin dimple. Management
Surgical and anesthetic considerations
Patients must have early consultation with craniofacial and orthopaedic surgeons, when craniofacial, clubfoot, or hand correction is indicated to improve function or aesthetics. Operative measures should be pursued cautiously, with avoidance of radical measures and careful consideration of the abnormal muscle physiology in Freeman–Sheldon syndrome.
Smoking has long been linked to RA and worsens articular disease as well as rheumatoid lung disease. Exposure to cigarette smoke leads to the activation of PADI enzymes that deaminate arginine to citrulline, producing autoantigens like citrullinated collagen and fibrinogen. Autoantigenic peptides containing citrulline residues are preferentially bound by HLA-DRB SE proteins and are presented to T cells, which interact with CCP-specific B cells found at sites containing autoantigen and produce inflammatory cytokines and autoantibodies, which accelerate disease. Bacterial or viral infections of the respiratory tract may also exacerbate pulmonary inflammation and rheumatoid lung disease. Diagnosis
The diagnosis of RA was formerly based on detection of rheumatoid factor (RF). However, RF is also associated with other autoimmune diseases. The detection of anti-CCP is currently considered the most specific marker of RA. The diagnosis of rheumatoid lung disease is based on evaluation of pulmonary function, radiology, serology and lung biopsy. High resolution CT scans are preferred to chest X-rays due to their sensitivity and specificity.Associated doctors to diagnosis this properly would be a Rheumatologists or Pulmonologist. Within a physical examination doctors could find possible indications, such as hearing crackles (rales) when listening to the lungs with a stethoscope. Or, there may be decreased breath sounds, wheezing, a rubbing sound, or normal breath sounds. When listening to the heart, there may be abnormal heart sounds.