Connectome changes have long been suspected to be involved in the sensory pathophysiology and most recently a range of circuit alterations have been shown, involving structurally increased local connectivity and functionally decreased long-range connectivity.In addition, FMRP has been implicated in several signalling pathways that are being targeted by a number of drugs undergoing clinical trials. The group 1 metabotropic glutamate receptor (mGluR) pathway, which includes mGluR1 and mGluR5, is involved in mGluR-dependent long term depression (LTD) and long term potentiation (LTP), both of which are important mechanisms in learning. The lack of FMRP, which represses mRNA production and thereby protein synthesis, leads to exaggerated LTD. FMRP also appears to affect dopamine pathways in the prefrontal cortex which is believed to result in the attention deficit, hyperactivity and impulse control problems associated with FXS. The downregulation of GABA pathways, which serve an inhibitory function and are involved in learning and memory, may be a factor in the anxiety symptoms which are commonly seen in FXS. Diagnosis
Cytogenetic analysis for fragile X syndrome was first available in the late 1970s when diagnosis of the syndrome and carrier status could be determined by culturing cells in a folate deficient medium and then assessing for "fragile sites" (discontinuity of staining in the region of the trinucleotide repeat) on the long arm of the X chromosome. This technique proved unreliable, however, as the fragile site was often seen in less than 40% of an individuals cells.
Livedoid dermatitis is a iatrogenic cutaneous reaction that occurs immediately after a drug injection. It presents as an immediate, extreme pain around the injection site, with overlying skin rapidly becoming erythematous, violaceous, or blanched ("ischemic pallor"): 124  and sometimes with reticular pattern. The reaction eventually leads to variable degrees of necrosis to the skin and underlying tissue. The wound eventually heals, but can lead to atrophic, disfiguring scarring. The reaction is associated with a range of both injection sites and drugs. It was first reported by Freudenthal in 1924 following an injection of bismuth salts for syphilis. Although initial reports were following intramuscular injections, the reaction has since also been reported following subcutaneous, intravenous, and intraarticular injections. Livedoid dermatitis has been reported to occur with many different drug injections, including: penicillins, local anesthetics (e.g. lidocaine), vaccines (e.g. Dtap), corticosteroids, NSAIDs, and more. Presentation
Pathogenesis
The cause of this condition is poorly understood. Microscopic examination of affected tissue shows ischemic necrosis, and so various hypotheses exist to explain this ischemia, including vasospasm from needle prick, the injected drug, or cold compresses applied to the wound. Diagnosis
The diagnosis is mainly clinical. Skin biopsies of the site show necrosis caused by ischemia. Radiographic imaging may help to delineate the extent of the wound. Treatment
Depending on the extent and state of infection of the wound, the condition may require antibiotics, wound debridement in early stages, and corrective plastic surgery in late stages. See also
Injection site reactions
List of cutaneous conditions


== References ==