Acrania anencephaly sequence is the progression from a relatively normal-appearing exposed brain due to an absent cranium (acrania) to an amorphous brain mass (exencephaly) to no recognisable brain tissue (anencephaly) 1.
The acrania anencephaly sequence begins with acrania, which is the most common anomaly affecting the central nervous system with an incidence of ~1:1000 pregnancies 1.
The abnormality occurs at the beginning of the fourth week of gestation when the anterior neuropore closes. The normal migration of mesenchymal tissue which is supposed to form the cranium does not occur. The overlying ectoderm remains the only covering as a thin amnion-like membrane. The calvarium, muscles of the scalp and the dura are not formed. In the absence of induction from the neurocranium, the cerebral tissue fails to differentiate into two hemispheres 2.
Acrania exposes the brain to the amniotic fluid with a risk of friction with the uterine wall, placenta and fetal parts; this condition is called exencephaly 3. In this circumstance, the unprotected brain tissue undergoes progressive destruction and degeneration due to mechanical and chemical trauma, leading to complete or almost complete disappearance of the brain from 14 weeks' gestation onward. The damaged brain tissue can be seen on ultrasound as echogenic particles in the amniotic fluid 4.
In the first trimester scans, there is a normal amount of brain tissue present which when seen in the coronal plane of fetus results in the Mickey Mouse sign due to two semicircular structures floating above the fetal face just like the rounded ears of Mickey Mouse.
In the second trimester, a significant amount of brain tissue is lost, resulting in the frog face sign due to an absence of recognisable tissue superior to the level of the fetal orbits 3.
As the sequence progresses further and acrania evolves, the amniotic fluid surrounding the fetus becomes echogenic with fine ground glass appearance (simulating an endometrioma or normal testis appearance).
- 1. Fong KW, Toi A, Salem S et-al. Detection of fetal structural abnormalities with US during early pregnancy. Radiographics. 2004;24 (1): 157-74. doi:10.1148/rg.241035027 - Pubmed citation
- 2. Mannes EJ, Crelin ES, Hobbins JS et-al. Sonographic demonstration of fetal acrania. AJR Am J Roentgenol. 1982;139 (1): 181-2. doi:10.2214/ajr.139.1.181 - Pubmed citation
- 3. Chatzipapas IK, Whitlow BJ, Economides DL. The 'Mickey Mouse' sign and the diagnosis of anencephaly in early pregnancy. Ultrasound Obstet Gynecol. 1999;13 (3): 196-9. doi:10.1046/j.1469-0705.1999.13030196.x - Pubmed citation
- 4. Cafici D, Sepulveda W. First-trimester echogenic amniotic fluid in the acrania-anencephaly sequence. J Ultrasound Med. 2004;22 (10): 1075-9. Pubmed citation