Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres, typically occurring between the 18th and 28th day of gestation. Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy. The condition also occurs in other species. Holoprosencephaly is estimated to occur in approximately 1 in every 250 conceptions and most cases are not compatible with life and result in fetal death in utero due to deformities to the skull and brain. However, holoprosencephaly is still estimated to occur in approximately 1 in every 8,000 live births.When the embryos forebrain does not divide to form bilateral cerebral hemispheres (the left and right halves of the brain), it causes defects in the development of the face and in brain structure and function. The severity of holoprosencephaly is highly variable. In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose, and upper lip. Signs and symptoms
Symptoms of holoprosencephaly range from mild (no facial/organ defects, anosmia, or only a single central incisor) to moderate to severe (cyclopia). The symptoms are dependent upon the classification type.There are four classifications of holoprosencephaly as well as a mild "microform". Alobar
Most severe form includes formation of synophthalmia (a single central eye), proboscis, and severe impairment. Semilobar
Can present with severely decreased distance between eyes, a flat nasal bridge, eye defects, cleft lip and palate, and severe impairment.
Increases in expression of such genes as Pax-2, as well as inhibition of Pax-6, from the notochord have been implicated in normal differentiation of cephalic midline structures. Inappropriate expression of any of these genes may result in mild to severe forms of holoprosencephaly. Other candidate genes have been located, including the SHH (holoprosencephaly type 3 a.k.a. HPE3), TGIF, ZIC2, SIX3 and BOC genes.Although many children with holoprosencephaly have normal chromosomes, specific chromosomal abnormalities have been identified in some patients (trisomy of chromosome 13, also known as Patau syndrome). There is evidence that in some families, HPE is inherited (autosomal dominant as well as autosomal or X-linked recessive inheritance). Features consistent with familial transmission of the disease (e.g., a single central maxillary incisor) should be carefully assessed in parents and family members. Non-genetic factors
Numerous possible risk factors have been identified, including gestational diabetes, transplacental infections (the "TORCH complex"), first trimester bleeding, and a history of miscarriage. As well, the disorder is found twice as often in female babies. However, there appears to be no correlation between HPE and maternal age.There is evidence of a correlation between HPE and the use of various drugs classified as being potentially unsafe for pregnant and lactating mothers. These include insulin, birth control pills, aspirin, lithium, thorazine, retinoic acid, and anticonvulsants. There is also a correlation between alcohol consumption and HPE, along with nicotine, the toxins in cigarettes and toxins in cigarette smoke when used during pregnancy. Prognosis
HPE is not a condition in which the brain deteriorates over time.