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.

Holoprosencephaly is estimated to occur in approximately 1 in every 250 conceptions[1] and most cases are not compatible with life and result in fetal death in utero due to deformities to the skull and brain.

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.

[1] Symptoms of holoprosencephaly range from mild (no facial/organ defects, anosmia, or only a single central incisor) to severe (cyclopia).

[1] In holoprosencephaly, the neural tube fails to segment, resulting in incomplete separation of the prosencephalon at the fifth week of gestation.

Mutations in the gene encoding the SHH protein, which is involved in the development of the central nervous system (CNS), can cause holoprosencephaly.

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.

[18] Numerous possible risk factors have been identified, including gestational diabetes, transplacental infections (the "TORCH complex"), first trimester bleeding, and a history of miscarriage.

These abnormalities are usually recognized shortly after birth or early in life and only occur if areas of the brain controlling those functions are fused, malformed or absent.

Most children with HPE are at risk of having elevated blood sodium levels during moderate-severe illnesses that alter fluid intake/output, even if they have no previous diagnosis of diabetes insipidus or hypernatremia.