Acrania

Acrania is a rare congenital disorder that occurs in the human fetus in which the flat bones in the cranial vault are either completely or partially absent. The cerebral hemispheres develop completely but abnormally. The condition is frequently, though not always, associated with anencephaly. The fetus is said to have acrania if it meets the following criteria: the fetus should have a perfectly normal facial bone, a normal cervical column but without the fetal skull and a volume of brain tissue equivalent to at least one-third of the normal brain size.

Causes

Genetics

Recent work has identified mutations in the hedgehog acyltransferase (HHAT) gene that have caused acrania along with holoprosencephaly and agnathia. The mutation in HHAT which causes this disease is a loss-of-function mutation. 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.