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.
Lobar
Can present with decreased distance between eyes, a flat nasal bridge, closely spaced nostrils, mental and locomotion delays may be present. Syntelencephaly or middle interhemispheric variant of holoprosencephaly (MIHV)
Mild phenotypic presentation which can present with flat nasal bridge, metopic prominence, shallow philtrum, and possible mental and locomotion delays. "Microform"
Mild phenotypic presentation with reduced distance between eyes, sharp nasal bridge, single maxillary central incisor. Diagnosis
Holoprosencephaly is typically diagnosed during fetal development when there are abnormalities found on fetal brain imaging, however it can also be diagnosed after birth. The Protocol for diagnosis includes neuroimaging (Ultrasound or fetal MRI prior to birth or Ultrasound, MRI or CT post birth), syndrome evaluation, cytogenetics, molecular testing, and genetic counseling.There are four classifications of holoprosencephaly as well as a “microform". These classifications can be distinguished by their anatomical differences.