Holoprosencephaly

Also known as: Alobar HPE

Background

Holoprosencephaly (HPE) is a series of brain malformations in which there is incomplete development of the cerebrum. Its effects on the child range from severe and lethal to mild and almost undetectable.

In the most severe form, alobar HPE, the cerebrum is a single U-shaped mass rather than being divided into right and left hemispheres. Death most often occurs before, during or soon after birth. Among liveborn children with alobar HPE, half will have died by four months of age, but survival for several years has been noted in a number of children.

Credits

Medical text written May 1998 by Dr M Barr Jr, University of Michigan, USA. Last reviewed March 2006 by Dr A Habel, Consultant Paediatrician, Great Ormond Street Hospital, London, UK and Dr M Lees, Consultant Geneticist, Institute of Child Health, London, UK.

What are the symptoms?

In the most severe form, alobar HPE, those who survive have profound learning disabilities, but they usually acquire some basic developmental skills such as visual tracking, responding to sound, smiling, and evidence of memory. Most children with alobar HPE will have seizures requiring anticonvulsant medication. Muscle spasticity and periods of marked irritability are present to some degree in all, and various medications may be helpful. Episodes of irregular breathing and pulse rate and highly variable body temperature control can be particularly troublesome. Endocrine problems due to pituitary gland malfunction may require medication. Feeding is a major problem, and tube or gastrostomy feeding is often recommended. Constipation is a common problem but can be managed successfully.

In the less severe forms, semilobar and lobar HPE, there is more complete development of the brain into right and left hemispheres. In general, survival is longer than with the alobar type, with many affected children living into adulthood, although early death is also common. Some degree of learning disability is the rule and is often severe. These more severely affected children will have many of the same problems found with alobar HPE. With the mildest forms of lobar HPE, the child may have minimal disability and a normal lifespan.

Associated malformation of the face is often present, most commonly with the alobar type of HPE. Cyclopia, median cleft lip and/or single nostril are markers of the severe end of the spectrum. Absent sense of smell and single maxillary central incisor tooth may be the only facial features at the mild end of the spectrum.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
HPE has many different causes. In most instances it is only one feature of a multiple malformation or chromosomal anomaly syndrome (particularly trisomy 13 Patau syndrome).

When it is an isolated malformation or accompanied only by face malformation it may be caused by an abnormal dominant gene (several different dominant genes have now been identified, but more remain to be discovered). It has also occurred among the offspring of mothers with insulin-dependent diabetes mellitus or severe alcohol abuse.

Prenatal diagnosis 
Prenatal detection of alobar HPE is possible by targeted ultrasound examination. The milder forms of HPE may not be evident by prenatal ultrasound examination.

Is there support?

There is no support group for holoprosencephaly in the UK. A support group outside of the UK exists for holoprosencephaly. Please ring our helpline for details.

Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. To meet other families with disabled children, join Contact’s closed (private) Facebook group.

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