There is no definitive mechanism to explain its development but it is likely that there are interactions between genes and the environment resulting in improper development of the first and sometimes second brachial arch. Genetic
Macrostomia can be partially classified as a heritable autosomal dominant disease. The responsible mutation is found on the short arm of chromosome 1 in locations 32-34 (1p32-1p34). The mutation is heterozygous meaning that it only occurs in one allele. A single base substitution in the 11th coding region of the gene PTCH2 changes an adenine to guanine. This results in a valine being incorporated instead of an isoleucine at the 147th position during translation of the resulting transmembrane protein (Val147Ile).The transmembrane protein encoded by PTCH2 is 1204 amino acids long and is involved with inhibiting the sonic hedgehog signalling pathway that is involved with development. PTCH2 inhibits the smooth frizzled class receptor (SMO) which when active is responsible for increasing transcription rates of many genes involved with development and differentiation. PTCH2 (Val147Ile) is a loss of function mutation which results in a lack of control of cell growth during development and links it to macrostomia. References


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Some degree of non-cyclical breast tenderness can normally be present due to hormonal changes in puberty (both in girls and boys), in menopause and during pregnancy. After pregnancy, breast pain can be caused by breastfeeding. Other causes of non-cyclical breast pain include alcoholism with liver damage (likely due to abnormal steroid metabolism), mastitis and medications such as digitalis, methyldopa (an antihypertensive), spironolactone, certain diuretics, oxymetholone (an anabolic steroid), and chlorpromazine (a typical antipsychotic). Also, shingles can cause a painful blistering rash on the skin of the breasts. Breast cancer
Some women who have pain in one or both breasts may fear breast cancer. However, breast pain is not a common symptom of cancer. The great majority of breast cancer cases do not present with symptoms of pain, though breast pain in older women is more likely to be associated with cancer. Diagnosis
Diagnosis involves breast examination, with medical imaging if only a specific part of the breast hurts. Medical imaging by ultrasound is recommended for all ages, well in those over 30 it is recommended together with mammography.Ruling out the other possible causes of the pain is one way to differentiate the source of the pain. Breast pain can be due to:

Medications can be associated with breast pain and include:

Diagnostic testing can be useful. Typical tests used are mammogram, excisional biopsy for solid lumps, fine-needle aspiration and biopsy, pregnancy test, ultrasonography, and magnetic resonance imaging (MRI). Treatment
In more than 75% of people the pain resolves without any specific treatment. Otherwise treatments may include paracetamol or NSAIDs.