What are the other Names for this Condition? (Also known as/Synonyms)

• Primary Acalvaria

What is Acalvaria? (Definition/Background information)

• Acalvaria is an extremely rare congenital malformation where the calvarial bones, dura mater, and associated muscles are absent, but the skull base and facial bones remain intact. The central nervous system is usually unaffected, although some neurological abnormalities may occur. The condition is characterized by a lack of a protective skull cap, with only a layer of skin covering the brain.
• Acalvaria is exceptionally rare, occurring in fewer than 1 in 100,000 births. The condition does not show a significant sex bias, but epidemiological data suggests it may be more common in females. The condition is often lethal at birth due to associated anomalies or trauma during delivery, but a few cases of survival have been reported.
• There are no well-established risk factors for Acalvaria. The condition is considered to be a result of random genetic mutations or errors in the post-neurulation development process. However, exposure to certain medications like ACE inhibitors and angiotensin II receptor antagonists during pregnancy has been associated with similar defects. The cause is unknown but is presumed to be a post-neurulation defect.
• The precise cause of Acalvaria remains unknown. It is thought to result from faulty migration of the membranous neurocranium relative to the ectoderm during embryonic development. This malformation is believed to occur after embryonic stage 11, indicating a post-neurulation defect.
• Symptoms of Acalvaria include the absence of calvarial bones, the dura mater, and associated muscles, with only a layer of skin covering the brain. Common symptoms may also include aplasia or hypoplasia of the cerebellum, calvarial skull defects, and various associated anomalies such as spina bifida and hydrocephalus.
• Acalvaria is diagnosed through prenatal imaging techniques, primarily using transvaginal ultrasound and magnetic resonance imaging (MRI). Diagnosis is confirmed by identifying the absence of the calvarial bones and dura mater while ensuring normal cerebral hemispheres and facial bones.
• Complications of Acalvaria can include severe head trauma during delivery, brain malformations, and associated anomalies such as spina bifida and hydrocephalus. The condition is often fatal at birth due to these complications.
• Treatment for Acalvaria is primarily supportive, focusing on managing any associated anomalies. While immediate treatment is conservative, potential options include skull reconstruction with bone grafting and cranioplasty at school age, although this is rarely pursued.
• Currently, there are no established methods for preventing Acalvaria due to its rarity and unknown cause. Prenatal monitoring through ultrasound and MRI can aid in early diagnosis, but prevention strategies are not well-defined.
• The prognosis for Acalvaria is generally poor, with most infants not surviving beyond birth due to associated anomalies or delivery trauma. A few cases of survival have been reported, but they often involve severe cognitive and physical impairments. The long-term outlook is limited, with very few documented cases of successful survival.

Who gets Acalvaria? (Age and Sex Distribution)

• Acalvaria is an exceptionally rare congenital malformation that occurs in fewer than 1 in 100,000 births.
• The condition does not show a strong preference for age or sex, though some reports suggest a slightly higher incidence in females.
• The rarity of Acalvaria means that data on age and sex distribution are limited, and most cases are diagnosed in the prenatal period or immediately at birth.

The condition's severity often leads to a lack of survival beyond birth, which affects the overall statistical representation.

What are the Risk Factors for Acalvaria? (Predisposing Factors)

Acalvaria is an extremely rare condition with no well-established risk factors.

• The primary suspected cause is a post-neurulation defect, which involves issues with the migration of mesenchymal tissue during embryonic development.
• Some research suggests that certain medications, like ACE inhibitors and angiotensin II receptor antagonists, might contribute to the condition if used during pregnancy.
• However, specific genetic or environmental risk factors for Acalvaria have not been definitively identified.

The condition's rarity and complexity mean that much of its etiology remains unknown.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Acalvaria? (Etiology)

• The precise cause of Acalvaria remains largely unknown, but it is generally attributed to a post-neurulation defect. This defect involves improper migration of mesenchymal tissue beneath the ectoderm during early fetal development.
• In a normally developing embryo, mesenchymal cells migrate to form the skull cap, but in Acalvaria, this process fails. This results in the absence of the calvarial bones while the skin overlying the brain remains intact.
• Additionally, some evidence suggests that exposure to certain medications, such as ACE inhibitors, during pregnancy may contribute to the development of this rare condition.

What are the Signs and Symptoms of Acalvaria?

Acalvaria is characterized by several distinctive signs and symptoms.

• The primary feature is the absence of the calvarial bones, which are the flat bones of the skull that form the brain's protective dome. Additionally, the dura mater and associated scalp muscles are missing.
• Common symptoms include abnormalities in the brain’s structure, such as aplasia or hypoplasia of the cerebellum, and defects in neuronal migration.
• Other potential features include spina bifida, hydrocephalus, and talipes.
• Infants may present with visible absence of the skull cap and associated complications due to exposed brain tissue.

How is Acalvaria Diagnosed?

Acalvaria is typically diagnosed through advanced imaging techniques.

• Prenatal diagnosis is often achieved using transvaginal ultrasound, which can reveal the absence of the skull bones.
• Magnetic resonance imaging (MRI) provides a more detailed view and helps confirm the diagnosis by distinguishing Acalvaria from similar conditions like anencephaly or encephalocele. The presence of skin overlying the brain matter, with normal cerebral hemispheres, is a key diagnostic feature.
• Postnatal diagnosis involves imaging and clinical examination to assess the extent of the malformation and any associated anomalies.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Acalvaria?

The complications of Acalvaria primarily stem from the severe structural abnormalities associated with the condition.

• Most notably, the absence of the skull cap can lead to fatal trauma during delivery, as the exposed brain is highly vulnerable.
• Infants with Acalvaria often face challenges such as severe neurological deficits, including potential brain malformations.
• Other complications may include issues related to associated anomalies like spina bifida, cardiac abnormalities, and respiratory problems.

Due to the rarity of the condition, the full range of potential complications is not entirely known, but they can be significant and impact survival and quality of life.

How is Acalvaria Treated?

Treatment for Acalvaria primarily focuses on supportive care and managing associated anomalies.

• In the newborn period, care is usually conservative, aiming to provide comfort and address any immediate health concerns.
• Although spontaneous bone growth has been observed in some cases of skull abnormalities, most affected infants do not survive past birth due to the severity of the malformation.
• For those who do survive, surgical interventions like skull reconstruction through bone grafting or cranioplasty may be considered later in childhood.
• However, such treatments are limited and typically only pursued in specific cases where the infant shows potential for survival and development.

How can Acalvaria be Prevented?

• Preventing Acalvaria is challenging due to its rarity and the unknown exact cause of the condition.
• Since Acalvaria is a congenital malformation that occurs early in fetal development, there are no established preventive measures.
• However, comprehensive prenatal care, including routine ultrasounds and potentially genetic counseling for at-risk families, may help in early diagnosis.
• For future pregnancies, avoiding known teratogens and ensuring optimal maternal health could potentially reduce the risk of similar congenital conditions.

Despite these measures, predicting and preventing Acalvaria remains complex due to its unpredictable nature.

What is the Prognosis of Acalvaria? (Outcomes/Resolutions)

The prognosis for Acalvaria is generally poor due to the severe nature of the condition.

• Most infants with Acalvaria do not survive beyond birth due to associated anomalies or trauma during delivery.
• The few cases of survival have shown that affected infants often face significant challenges, including severe cognitive and physical disabilities.
• Despite occasional survival, long-term outcomes are typically adverse, with most infants not living past infancy.

Survivors may require extensive medical care and surgical interventions.

Additional and Relevant Useful Information for Acalvaria:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/