Anencephaly

Anencephaly is an extreme form of neural tube defect (NTD) in which a baby is born without parts of the brain and skull. Acrania, or absence of the skull vault, leads to exencephaly, or protrusion of the brain. The cerebral hemispheres are exposed to amniotic fluid, which results in destruction of tissues.

The clinical features of anencephaly are:

• absence of forebrain;
• absence of cerebrum;
• absence of bony covering over the back of the head;
• presence of some basic reflexes (however, without the cerebrum there can be no consciousness and the baby cannot survive).

There is also an increased chance of other congenital malformations, including:

• folding of the ears;
• cleft palate; and
• congenital heart anomalies.

Anencephaly is a complex condition that is likely caused by the interaction of multiple genetic and environmental factors. Some of the genes involved have been identified. They include the following.

• MTHFR, which provides instructions for making a protein that is involved in processing folate (also called vitamin B9). While a deficiency in this vitamin is an established risk factor for NTDs, there are many others that can contribute.
• MARCKSL1 (also known as MacMARCKS), which is active during neural tube development.
• FOXN1, a gene that is important for the proper development of the central nervous system.

However, no genes appear to play a major role in causing anencephaly, and the exact cause remains unknown.

The most significant environmental factor that has been identified for anencephaly, along with other neural tube defects, is folate deficiency. Taking folic acid supplements prior to conception and in early pregnancy is recommended to reduce the risk.

Anencephaly is typically diagnosed through fetal ultrasound scan. It can be detected as early as the first trimester. Absence of brain tissue and the absence of the posterior portion of the cranial vault can be visualised.

Raised alpha-fetoprotein (AFP) levels in maternal blood and amniotic fluid are typically seen.

Postnatally, absence of the posterior part of the skull, absence of brain tissue, absence of the scalp and the presence of exposed cranial nerve tissue is observed.

Most cases of anencephaly are sporadic, which means that they occur in people with no history of the condition in their family. A small percentage of cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance.

For parents who have had a child with anencephaly, the probability of having another affected child is increased compared with the probability in the general population. After having one child with anencephaly, the recurrence risk is 2%–5%, rising to 10% if the parents have had two affected children. This is similar to other NTDs.

If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Anencephaly is usually diagnosed during routine pregnancy scans and can typically be identified at the first trimester or dating scan. Prognosis is very poor, and termination of pregnancy should be discussed. Almost all babies born with anencephaly will die shortly after birth.

If the family chooses to continue the pregnancy, routine ongoing fetal medicine appointments are unnecessary; however, these pregnancies are often complicated by significant polyhydramnios at later gestations, which may warrant further review.

Delivery planning should be made based on maternal risks, and vaginal delivery is not contraindicated. Early induction of labour may be considered in order to facilitate a vaginal birth.

There is no known cure or standard treatment for anencephaly.

Case reports of babies with anencephaly becoming organ donors after delivery are available, and this is an option that could be discussed in a sensitive manner with parents.

If planning future pregnancies, women who have had a previous pregnancy affected by anencephaly are recommended to take a higher dose of folic acid (5 mg instead of 0.4 mg, per day) before getting pregnant and up until 12 weeks of pregnancy.

For clinicians

• Medline Plus (National Library of Medicine): Anencephaly
• NHS England: National Genomic Test Directory
• The Fetal Medicine Foundation: Acrania

References:

• Sebold CD, Melvin EC, Siegel D and others. ‘Recurrence risks for neural tube defects in siblings of patients with lipomyelomeningocele‘. Genetics in Medicine 2005: volume 7, issue 1, pages 64–67. DOI: 10.1097/01.GIM.0000151158.09278.2B

For patients

• Antenatal Results & Choices
• Gov.uk Guidance: Anencephaly: Information for parents
• Shine: Anencephaly