Acrania

There are no known family ties in acrania and recurrence rates are extremely low. Not much is known about the exact mechanism involved in acrania. It is hypothesized that like other developmental malformations, there are multiple origins for acrania.

Recent work has identified mutations in the hedgehog acyltransferase (HHAT) gene that have caused acrania along with holoprosencephaly and agnathia.[3] The mutation in HHAT which causes this disease is a loss-of-function mutation.[3] Before this discovery in 2010, HHAT was known to play a role in the sonic hedgehog pathway. When HHAT contains a loss-of-function mutation, less HHAT protein is produced. HHAT is necessary for the production of Hedgehog (Hh) proteins post-transcriptionally. As HHAT production decreases, production of long-range Hh proteins decreases proportionally. Decreases in Hh| production disturb the production of extracellular signal-regulated kinases, bone morphogenetic proteins, and fibroblast growth factors, all of which play important roles in craniofacial patterning. Disruption of these pathways leads to abnormal bone and cartilage formation causing acrania and multiple other craniofacial patterning problems.[3]

Little genetic counseling can be offered for acrania because the genetic origins are not fully understood. In order to make genetic counseling for families easier this disease is often differentially diagnosed with other diseases that can occur at the same time such as anencephaly and acalvaria, though these diseases may not always occur simultaneously.[1] While this disease is tragic, reoccurrence rates are extremely low so genetic counseling is not always necessary.[1]

During amniotic band syndrome (ABS), fibrous bands may entrap various parts of the developing fetus causing malformations. When these fibrous bands form around the developing skull, the bones will not form properly. ABS occurring in the developing brain neural tissue is one cause of acrania.[4] When ABS is the cause of acrania the fibrous bands cannot be detected through ultrasound.[4]

Mesenchyme is formed in the developing embryo and will eventually become cartilage and bone. When ectodermal mesenchyme fails to migrate into the head region of the embryo, the skull will not be able to form. What exactly causes the failure of mesenchymal migration is unknown.[2]