Anencephaly: Symptoms, Types, Causes and Treatment

Anencephaly is one of the most severe neural tube defects (NTDs), characterized by the incomplete development of the brain, skull, and scalp. This congenital condition has a profound impact not just on affected infants, but also on families and communities. Understanding anencephaly—from its symptoms and types, to its causes and treatment options—is vital for healthcare professionals, expecting parents, and anyone invested in maternal and child health. In this article, we synthesize current research to provide a comprehensive, evidence-based overview of anencephaly.

Symptoms of Anencephaly

Anencephaly typically presents with unmistakable symptoms at birth or even before, detected through prenatal imaging. Recognizing these symptoms helps in early diagnosis, informed decision-making, and proper management.

Primary Feature	Description	Timing	Source(s)
Absence of brain	Missing major portions of brain (forebrain, cerebrum)	At birth/prenatal	5, 7
Skull defect	Cranial vault and scalp are absent or malformed	At birth/prenatal	1, 7
Facial anomalies	Abnormal facial development, flattened features	At birth	7
Reflexes present	Brainstem reflexes (breathing, responses) intact	At birth	7

Table 1: Key Symptoms

Understanding the Symptoms

Anencephaly is distinguished by the absence of large parts of the brain, particularly the cerebrum, which is responsible for thought, coordination, and consciousness. The cerebral hemispheres, which form the bulk of the brain tissue, are typically missing, leaving only rudimentary brainstem structures. This primary anomaly is often accompanied by the absence of the skull (cranial vault) and scalp, exposing the remaining neural tissue 5, 7.

Physical Manifestations

• Cranial Defects: Infants are usually born without the upper part of the skull, resulting in exposed brain tissue that is not covered by bone or skin 1, 7.
• Facial Abnormalities: The face may appear flattened or malformed due to the absence of supporting cranial structures 7.
• Brainstem Reflexes: While higher brain functions are absent, some infants may display basic reflexes such as breathing or responses to touch, as the brainstem can be partially preserved 7.

Detection

Advances in prenatal ultrasonography allow for early detection of anencephaly, often as early as the first trimester. This enables parents and healthcare providers to prepare for the outcome and consider options for pregnancy management 7.

Types of Anencephaly

Though anencephaly is generally understood as a single condition, there are several subtypes and related neural tube defects. Recognizing these distinctions is critical for accurate diagnosis and genetic counseling.

Type/Subtype	Distinctive Feature	Association/Overlap	Source(s)
Classical	Complete absence of brain/skull	Most common	1, 5
Acrania	Absence of cranial bones, brain present initially	May progress to anencephaly	1
Craniorachischisis	Anencephaly with open spinal cord	Severe, rare	1, 6
Exencephaly	Brain exposed, not yet degraded	Precursor to anencephaly	3

Table 2: Types and Related Conditions

Classical Anencephaly

This is characterized by the almost complete absence of the brain and cranial vault, and is the form most frequently encountered in clinical practice. These infants are either stillborn or die shortly after birth 1, 5.

Acrania

In acrania, the cranial bones fail to develop, but brain tissue may initially be present. However, this exposed brain tissue rapidly degenerates, often progressing into anencephaly as gestation continues 1.

Craniorachischisis

A more extensive defect, craniorachischisis, occurs when anencephaly is accompanied by a continuous open spinal column. This reflects a broader failure of neural tube closure, leading to both cranial and spinal involvement 1, 6.

Exencephaly

Exencephaly is considered a precursor to anencephaly. In this stage, the brain develops outside the skull and, being unprotected, undergoes degeneration and collapse, resulting in anencephaly 3. Experimental studies in animals show that exencephaly can convert to anencephaly due to tissue disintegration 3.

Causes of Anencephaly

The origins of anencephaly are complex and multifactorial, involving both genetic and environmental factors. Understanding these causes is crucial for prevention, genetic counseling, and future research.

Factor	Role/Impact	Examples/Evidence	Source(s)
Genetic mutations	Direct role in neural tube development	TRIM36, PDGFRA, MAT1A, etc.	5, 6
Environmental	Triggered in early pregnancy	Vitamin deficiencies, socioeconomic status	4, 7
Multifactorial	Both genetic & nongenetic interplay	Oligogenic inheritance	2, 6
Folic acid deficiency	Major modifiable risk factor	Preventable with supplements	7

Table 3: Causes and Risk Factors

Genetic Factors

Genetic mutations have been identified in several families and populations with a high incidence of anencephaly. Notably, mutations in the TRIM36 gene have been linked to autosomal recessive inheritance of anencephaly in some families 5. Other rare, damaging variants in genes such as PDGFRA, MAT1A, and NOS2 have also been identified, supporting the idea of genetic heterogeneity and possible oligogenic inheritance (where multiple genes contribute to risk) 6.

• Autosomal recessive pattern: Some cases show clear autosomal recessive inheritance, meaning both parents must carry the mutated gene for the condition to manifest in the child 5.
• Genetic counseling: The recurrence risk is generally low for isolated anencephaly, but higher for syndromic forms or when other family members are affected 2.

Environmental Factors

Environmental influences are strongly implicated, often acting during the critical early weeks of pregnancy:

• Folic acid deficiency: Perhaps the most significant modifiable risk factor. Lack of folic acid before and during early pregnancy increases the risk of neural tube defects, including anencephaly. Periconceptional folic acid supplementation can significantly reduce prevalence 7.
• Maternal health and nutrition: Poor nutrition, low socioeconomic status, and certain geographic or ethnic backgrounds are associated with higher rates 4.
• Toxins and medications: Exposure to certain environmental toxins or medications during pregnancy may also play a role, though definitive causative agents remain largely unproven 4.

Multifactorial Inheritance

Most cases of anencephaly are considered multifactorial, resulting from an interplay between genetic susceptibility and environmental triggers 2 6. This complexity makes precise prediction and prevention challenging.

Treatment of Anencephaly

Unfortunately, there is currently no cure for anencephaly. Management focuses on prevention, supportive care, and counseling for affected families. Advances in prenatal diagnosis have shifted the emphasis toward early detection and prevention.

Approach	Purpose/Outcome	Population/Timing	Source(s)
Prenatal diagnosis	Early identification, informed decision-making	Pregnant women	7
Pregnancy management	Delivery planning, minimize maternal complications	Late pregnancy	7
Supportive care	Comfort for infant and family, palliative focus	Postnatal, short-term	7
Prevention	Folic acid supplementation, education	Preconception/early pregnancy	7

Table 4: Treatment and Management Strategies

Prenatal Diagnosis and Counseling

• Ultrasound: High-resolution ultrasound can detect anencephaly as early as the first trimester, allowing parents and providers to discuss options 7.
• Genetic counseling: Families with a history of neural tube defects benefit from genetic counseling, discussing recurrence risks and preventive measures 2 6.

Pregnancy and Delivery Management

• Delivery planning: Most affected pregnancies result in stillbirth or early neonatal death. Induction of labor is often considered when anencephaly is diagnosed, with caesarean section rarely required unless for maternal indications 7.
• Maternal health: Care is taken to minimize risk to the mother, especially if the pregnancy is complicated by polyhydramnios (excess amniotic fluid) or other obstetric issues 7.

Postnatal Care

• Supportive/palliative care: Infants born with anencephaly are provided with comfort care, focusing on dignity and minimizing discomfort. Life-sustaining interventions are generally not indicated due to the condition’s lethality 7.
• Emotional support: Psychological counseling and support groups are essential for families coping with the diagnosis and loss 7.

Prevention

• Folic acid supplementation: The most effective preventive strategy is ensuring adequate folic acid intake before conception and during early pregnancy. Public health campaigns and supplementation programs have demonstrably reduced the incidence of anencephaly in many regions 7.
• Education: Raising awareness about the importance of periconceptional folic acid is critical, especially in areas with high prevalence 7.

Conclusion

Anencephaly remains a challenging and tragic congenital disorder, but advances in research and public health continue to improve prevention and management. Here’s a summary of the key points covered:

• Symptoms: Major features include absence of the brain, skull, and scalp, often detected prenatally via ultrasound 1, 5, 7.
• Types: Includes classical anencephaly, acrania, craniorachischisis, and exencephaly, reflecting a spectrum of neural tube closure defects 1, 3, 6.
• Causes: Result from a complex interplay of genetic mutations (such as in TRIM36), environmental factors (notably folic acid deficiency), and multifactorial inheritance 2, 4, 5, 6, 7.
• Treatment: No cure exists; focus is on prevention (especially folic acid supplementation), early diagnosis, supportive care, and counseling for families 7.

Continued research, early detection, and effective prevention strategies remain the cornerstones for reducing the burden of anencephaly worldwide.