Sign Up for a Free Account
  • Updated 09.12.2022
  • Released 10.10.1994
  • Expires For CME 09.12.2025

Anencephaly and other neural tube defects



Anencephaly is a severe and uniformly lethal malformation that results from incomplete closure of the anterior neural tube, whereby fetuses or infants present with absent calvarial and cerebral structures. In this article, the author discusses the etiology, pathogenesis, genetic contribution, and epidemiology of anencephaly as well as approaches toward the diagnosis and prevention of this and other neural tube defects.

Key points

• Anencephaly represents one of the major forms of neural tube defect, along with encephalocele and spina bifida.

• The prenatal administration of folic acid is essential in preventing neural tube defects; other vitamins and dietary substances (eg, inositol) may exert a preventative effect as well.

• Some cases of anencephaly occur from mechanisms that do not involve folic acid (so-called "folate-resistant" neural tube defects, although a more accurate term would be “folate nonresponsive”).

Historical note and terminology

Anencephaly was not described in recognizable form until the 16th century (15; 176).

Anencephaly belongs to a group of congenital malformations known collectively as "neural tube defects" (which also include encephalocele and myelomeningocele). The common neuroanatomical feature in anencephaly is an open defect in the calvaria and skin. The defect varies in size but is often so large that the predominant feature is a degenerated and hemorrhagic mass of tissue lying on an essentially exposed basicranium. Numerous classifications and synonyms have led to confusion about the spectrum of anencephaly.

Terminology of anencephaly and similar or related disorders. Acephalus, acrania, anencephalus, cranioschisis, and cranial or cerebral dysraphia are commonly used, but not necessarily correctly. Acephaly is the congenital absence of a head.

"Acadiacus acephalus monopus" (after Otto) -- heartless, headless, one-legged fetus

(Source: Küstner O. Anomalien des Fötus. In: Die vom Fötus abhängenden Schwangerschafts- und Geburtsstörungen. Handbuch der Geburtshülfe 1888;2:497-815.)

The term "acrania," literally meaning the absence of the cranium, is used to refer to a rare congenital anomaly in which the flat bones of the cranial vault are partially or completely absent, although the bones at the base of the skull are normally present, often with abnormal development of the cerebral hemispheres. The condition is frequently, though not always, associated with anencephaly.


(Source: Photograph by Dr.sachin23 on December 29, 2011. Creative Commons Attribution-Share Alike 3.0 Unported License,

The term "acalvaria" is often taken as a synonym for acrania. According to the Orphanet definition, primary acalvaria is defined as follows (ORPHA:945):

A rare malformation characterized by missing scalp and flat bones over an area of the cranial vault. The size of the affected area is variable. In rare cases, acalvaria involves the whole of the dome-like superior portion of the cranium comprising the frontal, parietal, and occipital bones. Dura mater and associated muscles are absent in the affected area but the central nervous system is usually unaffected, although some neuropathological abnormality is often present (eg, holoprosencephaly or gyration anomalies). Skull base and facial bones are normal.

Neural tube defects are malformations of the brain and spinal cord that occur when the neural tube does not close properly. These types of birth defects develop very early during pregnancy, often before a woman knows she is pregnant. Neural tube defects include forms of anencephaly (holoanencephaly, meroanencephaly, and craniorachischisis), iniencephaly, encephalocele, and forms of spina bifida (myelomeningocele, meningocele). The most common neural tube defects are anencephaly and spina bifida.

Anencephaly, or anencephalus, is a severe form of anterior neural tube defect in which the brain is absent.

Isolated anencephaly/exencephaly is defined as follows (ORPHA:1048):

This malformation is characterized by the total or partial absence of the cranial vault and the covering skin, the brain being missing or reduced to a small mass. Most cases are stillborn, although some infants have been reported to survive for a few hours or even a few days. ... Anencephaly is likely to be multifactorial, the result of gene-environment interactions. ... Familial cases with a seemingly autosomal recessive mode of inheritance have been described but most cases are sporadic.

Cranioschisis is a congenital abnormality characterized by the failure of the bones of the skull to close, whereas rachischisis is a neural tube defect in which an extended portion of the spinal cord remains open. These often occur together as craniorachischisis, a neural tube defect in which both the brain and spinal cord remain open to varying degrees.

One classification that provides a framework for all types of anencephaly differentiates craniorachischisis (head and spine are open) from holoacrania (cranial defect extends through the foramen magnum) and meroacrania (partial cranial defect not extending to foramen magnum). However, the latter two disorders are most often referred to in terms of the brain structures involved (ie, holoanencephaly and meroanencephaly, respectively) rather than solely in terms of the extent of bony abnormality.

Cranial dysraphism collectively refers to anterior neural tube defects, anencephaly, and encephaloceles that result from failure of closure of the anterior end of the neural tube. In contrast, spinal dysraphism, or spina bifida, refers to posterior neural tube defects that result from failure of closure of the caudal end of the neural tube.

Exencephaly is a malformation of the neural tube with a large amount of protruding brain tissue and absence of calvarium. Animal studies generally use the term "exencephaly" to refer to a disorder equivalent to anencephaly, and in the terminology database they are synonyms.