Holoprosencephaly is a condition present from birth that is caused by failure of proper development of a baby’s brain and face early in pregnancy (i.e., 5 weeks from the last menstrual period). Holoprosencephaly is characterized by the degree of forebrain separation and can range from mild to severe depending on how much separation occurs.
Alobar – the most severe form, where the brain does not divide into two halves at all
Semilobar- the brain is partially divided
Lobar- the mildest of the classic forms, where most of the brain is divided but the separation is incomplete
Middle interhemispheric variant and microforms- milder forms that may cause fewer or less obvious symptoms
Holoprosencephaly occurs in 1 in 10,000 live births. It is more common early in pregnancy, affecting around 1 in 172 conceptions, making it a common congenital defect.
Mutations in ZIC2can lead to all forms of HPE, both classic and middle interhemispheric variant.
Individuals with Holoprosencephaly commonly present with neurodevelopmental delays and seizure disorders alongside brain and facial abnormalities. ZIC2-associated Holoprosencephaly is characterized by distinct facial traits.
Holoprosencephaly has several causes, including chromosomal abnormalities in 25% of cases, syndromic causes in 75% if cases and mutations that occur in isolation in 25% of cases. There are 14 genes of which, when mutated, are linked to Holoprosencephaly, including ZIC2.
ZIC2