region of the body. Larger or segmental hemangiomas that span a large area can sometimes have underlying anomalies that may require investigation, especially when located on the face, sacrum, or pelvis. Unless ulceration occurs, an IH does not tend to bleed and is not painful. Discomfort may arise if it is bulky and blocks a vital orifice. Complications Almost no IHs are associated with complications. They may break down on the surface, called ulceration, which can be painful and problematic. If the ulceration is deep, significant bleeding and infection may occur in rare occasions. If a hemangioma develops in the larynx, breathing can be compromised. If located near the eye, a growing hemangioma may cause an occlusion or deviation of the eye that can lead to amblyopia. Very rarely, extremely large hemangiomas can cause high-output heart failure due to the amount of blood that must be pumped to excess blood vessels. Lesions adjacent to bone may cause erosion of the bone. The most frequent complaints about IHs stem from psychosocial complications. The condition can affect a person's appearance and provoke attention and malicious reactions from others. Particular problems occur if the lip or nose is involved, as distortions can be difficult to treat surgically. The potential for psychological injury develops from school age onward. Considering treatment before school begins is, therefore, important if adequate spontaneous improvement has not occurred. Large IHs can leave visible skin changes secondary to severe stretching that results in altered surface texture. Large segmental hemangiomas of the head and neck can be associated with a disorder called PHACES syndrome. Large segmental hemangiomas over the lumbar spine can be associated with dysraphism, renal, and urogenital problems in association with a disorder called LUMBAR syndrome. Multiple cutaneous hemangiomas in infants may be an indicator for liver hemangiomas. Screening for liver involvement is often recommended in infants with five or more skin hemangiomas. Causes The cause of hemangioma is currently unknown, but several studies have suggested the importance of estrogen signaling in proliferation. Localized soft-tissue hypoxia coupled with increased circulating estrogen after birth may be the stimulus. Also, a hypothesis was presented by researchers that maternal placenta embolizes to the fetal dermis during gestation, resulting in hemangiomagenesis. However, another group of researchers conducted genetic analyses of single-nucleotide polymorphism in hemangioma tissue compared to the mother's DNA that contradicted this hypothesis. Other studies have revealed the role of increased angiogenesis