User:Nthoman1/sandbox/Acephaly

Acephaly is a congenital disorder characterized by absence of the encephalic structure (head). Unlike anencephaly, which is characterized by the absence of a major portion of the brain, skull, and scalp, this type of cephalic disorder is more rare. It is possible for acephaly to occur in both a monozygotic twin and in a singleton pregnancy; however, singleton pregnancies are more uncommon. As of 2012, only 7 cases of acephaly have been reported in singleton pregnancies.

Etiology
Research for the causes of acephaly is ongoing. A connection to parental chromosomal abnormalities has yet to be found, and acephaly may therefore be environmental in cause. Evidence suggests acephaly is a sporadic event, as no familial recurrence has been reported. Depending on the type of pregnancy, the cause of acephaly differs. The most common mechanism within monozygotic twins is twin reversed arterial perfusion (TRAP). In this case, the acephalic fetus is a parasitic twin attached to an otherwise intact fetus. The parasitic twin displays acradiac acephaly (lacking both head and heart structures). The normally developing twin pumps blood to the acardiac acephalic fetus through artery-to-artery or venous-to-venous communications. Though survival rate of the donor fetus is decreased, they have a chance of survival through the implications of in utero interventions. In singlet pregnancies, the most commonly proposed mechanism for acephaly is amniotic band constriction, which is known to cause limb amputations through mechanical pressure. Acephalic fetuses in singleton pregnancies also characteristically show clubbed feet, likely due to movement restriction. Other etiopathological mechanisms suggested are attachment of the fetus’ head to the placenta causing movement restriction and decapitation, and the fertilization of the first polar body; however, neither have gained much attention.

Chromosomal review of acephalic fetuses has shown reports of chromosomal abnormalities such as euploidy, aneuploidy, mosaicism, translocations and deletions. In contrast, acephalic fetuses with normal karyotypes have also been reported. Large chromosomal abnormalities may predispose the fetus to errors in early development; however, due to the prevalence of normal karyotypic examples, such errors may not be necessary for acephaly.

Diagnosis
Acephaly can be diagnosed using obstetric ultrasonography. In singleton pregnancies, ultrasounds between the 11th and 14th weeks of pregnancy may show normal fetal development of other extremities, but lacking head and neck structures. <ref name="two" In these cases, diagnosis of acephaly is usually followed by medical abortion. Final diagnosis after abortion is confirmed by pathological and radiological examinations. Ultrasound of monozygotic twins will show a dependent fetus lacking a head, thorax, and upper extremities, while they may still show normal or accelerated development in lower extremities.

Epidemiology
The incidence of acephaly is approximated as every 1 in 35,000 births, as estimated by the prevalence of twinning and the fraction of twin gestations affected by this abnormality. This rare incidence has only been reported in approximately 500 cases worldwide.

Acephaly in Mice
A genetic basis for acephaly is found in mice models. Acephaly can be induced by the knockout of either Lim1 or OTX2 genes. Both encode homeodomain transcription factors which are highly conserved among vertebrates and are required for head formation and sensory organ development, respectively. Mice homozygous for the Lim-1 and Oxt-2 knockout lack anterior head structure, while the rest of the body shows normal development.