Holoprosencephaly (HPE)

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NINDS: ⁵² Holoprosencephaly is a disorder caused by the failure of the prosencephalon (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects. In most cases of holoprosencephaly, the malformations are so severe that babies die before birth. 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. There are three classifications of holoprosencephaly. Alobar, in which the brain has not divided at all, is usually associated with severe facial deformities. Semilobar, in which the brain's hemispheres have somewhat divided, causes an intermediate form of the disorder. Lobar, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly the baby's brain may be nearly normal. The least severe of the facial anomalies is the median cleft lip (premaxillary agenesis). The most severe is cyclopia, an abnormality characterized by a single eye located in the area normally occupied by the root of the nose, and a missing nose or a proboscis (a tubular-shaped nose) located above the eye. The least common facial anomaly is ethmocephaly, in which a proboscis separates closely-set eyes. Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely-set eyes.

MalaCards based summary: Holoprosencephaly, also known as holoprosencephaly sequence, is related to holoprosencephaly 9 and holoprosencephaly 7. An important gene associated with Holoprosencephaly is FGFR1 (Fibroblast Growth Factor Receptor 1), and among its related pathways/superpathways are Signal Transduction and Signaling by Hedgehog. Affiliated tissues include Primitive Streak, brain and eye, and related phenotypes are abnormal facial shape and holoprosencephaly

GARD: ¹⁹ Holoprosencephaly is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. There are 4 types of Holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disability and pituitary gland problems. Holoprosencephaly can be caused by genetic changes in any of at least 14 different genes; chromosome abnormalities; or agents that can cause birth defects (teratogens). It may also be a feature of several unique genetic syndromes. In many cases, the exact cause is unknown.

Orphanet: ⁵⁸ A rare complex brain malformation characterized by incomplete cleavage of the prosencephalon, and affecting both the forebrain and face and resulting in neurological manifestations and facial anomalies of variable severity.

Disease Ontology: ¹¹ A congenital nervous system abnormality characterized by failed or incomplete separation of the forebrain early in gestation; it is accompanied by a spectrum of characteristic craniofacial anomalies.

Wikipedia: ⁷⁵ Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo)... more...

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