The first hypothesis of its origin was developed in 1927 and proposed that a lack of blood supply to the lower limbs during their development is responsible for the defect. This "vascular steal" hypothesis was developed in response to the observed absence or severe underdevelopment of the aorta below the umbilical artery, which "steals" the blood supply from the lower limbs. Other hypotheses involve an insult to the embryo between 28 and 32 days affecting the caudal mesoderm, a teratogen exposure affecting the neural tube during neurulation, and a defect in the twinning process that either stops the process of caudal differentiation or generates a second primitive streak.Maternal diabetes mellitus has been associated with caudal regression syndrome and sirenomelia, although a few sources question this association. Prenatal cocaine exposure has also been suggested as an association with sirenomelia. Genetics
In animal models, several genes have been found to cause or be associated with sirenomelia. The srn (siren) gene is observed to cause hindlimb fusion in homozygous mice. Mice with knockouts or mutations in both tsg1 and bmp7 will also have hindlimb fusion. Diagnosis
Though obvious at birth, sirenomelia can be diagnosed as early as 14 weeks gestation on prenatal ultrasound. When there is low amniotic fluid around the fetus (oligohydramnios), the diagnosis is more difficult. Prognosis
Sirenomelia is usually fatal. Many pregnancies with a sirenomelic fetus spontaneously miscarry.
Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and symptoms may vary from mild to severe and usually start two to five days after exposure. Symptoms often come on fairly gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat. This can block the airway and create a barking cough as in croup. The neck may swell in part due to enlarged lymph nodes. A form of diphtheria which involves the skin, eyes or genitals also exists. Complications may include myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets. Myocarditis may result in an abnormal heart rate and inflammation of the nerves may result in paralysis.Diphtheria is usually spread between people by direct contact or through the air. It may also be spread by contaminated objects. Some people carry the bacterium without having symptoms, but can still spread the disease to others. The three main types of C. diphtheriae cause different severities of disease. The symptoms are due to a toxin produced by the bacterium. Diagnosis can often be made based on the appearance of the throat with confirmation by microbiological culture. Previous infection may not protect against infection.A diphtheria vaccine is effective for prevention and available in a number of formulations.