Anencephaly

The underlying cause of anencephaly is not fully understood. Like other forms of neural tube defects (NTDs), anencephaly is likely caused by the interaction of multiple genes and environmental factors, many of which remain unknown.

Variations in many genes may influence the risk of developing anencephaly. The best-studied gene thus far is the MTHFR gene, which gives the body instructions to make a protein used to process the vitamin folate (also called vitamin B9). A deficiency of folate is a known risk factor for NTDs. Other genes involved in folate processing, and the development of the neural tube, may also affect the risk.

Researchers have also looked at environmental factors that could contribute to the risk of anencephaly. Folate appears to play a significant role, and studies have shown that taking folic acid (a form of folate), before getting pregnant and very early in pregnancy, significantly reduces the risk to have a baby with a NTD. Other possible maternal risk factors for anencephaly include diabetes mellitus; obesity; exposure to high heat (such as a fever or use of a hot tub or sauna) in early pregnancy; and the use of certain anti-seizure medications during pregnancy.

Most cases of anencephaly are sporadic, which means they occur in people with no family history of anencephaly or other neural tube defects (NTDs). In some cases, it may be associated with a chromosome abnormality, a severe malformation syndrome, or disruption of the amniotic membrane. A small portion of cases have appeared to be familial, but it often does not have a clear inheritance pattern. In isolated populations, anencephaly has been suspected to be due to a single gene. In Iranian Jews, who have high rates of consanguinity (mating with family members), it is inherited in an autosomal recessive manner.

Parents who have had a child with anencephaly are at an increased risk to have another affected child (compared with the risk in the general population). Because most cases are believed to be multifactorial (due to interaction of genetic and environmental factors), the recurrence risk is estimated to be between 2% and 5% after a single case. If anencephaly is known to be associated with an underlying disorder, the recurrence risk may depend on that of the underlying disorder.

For women who have previously had a fetus or infant with anencephaly, the Centers for Disease Control and Prevention (CDC) recommends increasing the intake of folic acid to 4mg per day beginning at least one month prior to conception.

People who have had a pregnancy or child with anencephaly or another NTD, and have questions about future risk, are encouraged to speak with a genetic counselor or other genetics professional.

Developmental delay occurs in up to 15% of children under 5 years of age. Developmental delay can have many different causes, including genetic and environmental causes. Causes can be congenital (present at birth) or acquired with onset before or after birth. However, the specific cause of developmental delay often remains unknown.

It has been suggested that between 25% (1 in 4) to 50% (half) of cases of developmental delay (mainly global developmental delay or intellectual disability) may be genetic in origin. Genetic causes may include large chromosome abnormalities; a small deletion or duplication of genetic material; or disorders caused by changes (mutations) in a single gene. Furthermore, all types of inheritance have been reported. Still, a genetic cause of developmental delay often remains unidentified.

People with questions about the causes of developmental delay in a child and/or genetic testing are encouraged to consult with a developmental pediatrician and/or genetics professional.

Disorders that are associated with anencephaly include:

• folate deficiency
• maternal hypothermia
• trisomy 13
• trisomy 18
• Turner syndrome
• triploidy
• amniotic band syndrome
• limb/body wall defects
• Walker-Warburg syndrome

Anencephaly is a type of neural tube defect (NTD). If an NTD occurred in a previous pregnancy, there is up to a 4% chance of each future pregnancy also being affected with an NTD. However, taking the vitamin folic acid has been proven to reduce the chance of an NTD in future pregnancies. In one large research study, women who had a previous pregnancy affected by an NTD and who took folic acid prior to and during later pregnancies had an approximately 1% chance of having another pregnancy affected with an NTD.

The Centers for Disease Control and Prevention (CDC) recommends that every woman take 400 micrograms of folic acid daily for at least one month prior to becoming pregnant, and every day during the pregnancy as well, to reduce the chance of neural tube defects. In families with a history of anencephaly (a type of neural tube defect) in a previous pregnancy, it is recommended that the dose of folic acid be ten times higher, or 4 milligrams per day, beginning at least three months prior to becoming pregnant again and continuing every day during the pregnancy.

Most miscarriages are caused by chromosome abnormalities in the fertilized egg that make it impossible for the baby to develop. These chromosome abnormalities are most often due to random events (that are not inherited). In some cases, a genetic abnormality in the mother or father (such as a balanced translocation) increases the risk for a genetic abnormality in the baby and a subsequent miscarriage.

Other possible causes of miscarriage include environmental factors such as maternal drug or alcohol abuse; exposure to toxins; hormone problems; infection; obesity; physical abnormalities of the reproductive organs; problem with the body's immune response; maternal disease (such as uncontrolled diabetes); and/or smoking.

Miscarriages are extremely common, with about half of all fertilized eggs being lost spontaneously (usually before a woman knows she is pregnant). Among women who know they are pregnant, 15 to 20% will have a miscarriage.

Anencephaly is a type of neural tube defect characterized by abnormal development of the brain and the bones of the skull. The neural tube is a narrow channel that normally folds and closes between the 3rd and 4th weeks of pregnancy, forming the brain and spinal cord of the embryo. Anencephaly occurs when the 'cephalic' or head end of the neural tube fails to close, causing the absence of a major portion of the brain, skull, and scalp. Infants with this disorder are born without a forebrain (the front part of the brain) and a cerebrum (the thinking and coordinating part of the brain). The remaining brain tissue is often exposed (not covered by bone or skin). Affected babies are usually blind, deaf, unconscious, and unable to feel pain. Almost all babies with anencephaly die before birth, although some may survive a few hours or a few days after birth. Anencephaly is likely caused by an interaction between genetic and environmental factors, many of which remain unknown.

Recent studies have shown that the addition of folic acid (vitamin B9) to the diet of women of childbearing age may significantly reduce the incidence of neural tube defects. Therefore it is recommended that all women of childbearing age consume 0.4 mg of folic acid daily.

Because miscarriage, developmental delay, and anencephaly may each occur as isolated findings and can each be due to both genetic and environmental factors (or combinations of these factors), it is difficult to determine whether they may be related. If a specific underlying cause has been identified for one or more of these, estimating the recurrence risk for the same finding, or the likelihood of related findings, may be possible.

Some studies have found that pregnancies following miscarriages have an increased risk of a poor outcome. A miscarriage may indicate a higher risk of poor outcomes in subsequent pregnancies if the miscarriage and these outcomes are due to the same underlying cause, or if the miscarriage or its treatment is a risk factor in itself.

Several researchers have investigated the effect of miscarriages on the risk of neural tube defects (NTDs). In the 70s, it was proposed that the residues of pregnancy-related tissues that remain in the uterus after a pregnancy could potentially harm fetal development in the following pregnancy. Some studies have had findings in agreement with this, but others have found no evidence of this association. The authors in one study noted that their results suggest that women with a history of miscarriage have a greater risk of having children with anencephaly in subsequent pregnancies.This does not necessarily mean that the miscarriage itself is the cause, but that common mechanisms could be involved in causing both miscarriage and anencephaly.

Certain types of genetic tests may be appropriate in a fetus or person with a personal or family history of miscarriage, developmental delay, and/or anencephaly. However, because each of these can be due to various causes (many of which are unknown), it is difficult to predict whether genetic testing might be informative for a person with a family history of all of these.

People who have questions about genetic testing are strongly encouraged to consult with a genetic counselor or other genetics professional. A genetics professional can thoroughly evaluate the family history; address questions and concerns; assess recurrence risks; facilitate genetic testing if appropriate; and discuss reproductive options.

While we are not able to comment on your specific risk to have a child with anencephaly, research shows that once a child has been born with an open neural tube defect (ONTD) in the family, the chance for an ONTD to happen again is increased to 3 to 5 percent. It is important to understand that the type of neural tube defect can differ the second time. For example, one child could be born with anencephaly, while the second child could have spina bifida. For families with multiple occurrences of neural tube defects (NTDs), recurrence risks may be higher and must be determined on a case-by-case basis.

Couples who have had an affected baby or have a family history of NTDs should consult a genetic counselor to discuss risks to their future children. Genetic counselors can also discuss preventive measures such as vitamin therapy (a prescription for folic acid) that can decrease the recurrence risk for ONTDs.