Prognosis is poor. Previous research suggested a 100% mortality rate for those with acrania. This disease is rare, occurring in 1 in 20,000 live births.

In order to better manage an acrania diagnosis, early detection is of extreme importance so that actions may be taken to help the mother and child. Families may choose either to terminate the pregnancy, or to carry the child to term. Acrania may cause a fetus to spontaneously abort before reaching term.

Acrania can be diagnosed early in pregnancy through an ultrasound. This abnormality appears during the beginning or end of the fourth week of the fetus's development. An absence of the skull is needed in order to make a diagnosis. A presence of brain tissue will confirm the diagnosis of acrania and differentiate it from other developmental problems such as anencephaly.

Anencephaly can often be diagnosed before birth through an ultrasound examination. The maternal serum alpha-fetoprotein (AFP screening) and detailed fetal ultrasound can be useful for screening for neural tube defects such as spina bifida or anencephaly.

There is no cure or standard treatment for anencephaly and the prognosis for patients is death. Most anencephalic fetuses do not survive birth, accounting for 55% of non-aborted cases. Infants that are not stillborn will usually die within a few hours or days after birth from cardiorespiratory arrest.

Four recorded cases of anencephalic children surviving for longer periods of time are Stephanie Keene (better known as Baby K) of Falls Church, Virginia, USA, who lived for 2 years 174 days; Vitoria de Cristo, born in Brazil in January 2010 and surviving until July 17, 2012; Nickolas Coke of Pueblo, Colorado, USA, who lived for 3 years and 11 months, and died October 31, 2012; and Angela Morales, from Providence, Rhode Island, who live for 3 years and 9 months, and died December 16 2017.

In almost all cases, anencephalic infants are not aggressively resuscitated because there is no chance of the infant's ever achieving a conscious existence. Instead, the usual clinical practice is to offer hydration, nutrition, and comfort measures and to "let nature take its course". Artificial ventilation, surgery (to fix any co-existing congenital defects), and drug therapy (such as antibiotics) are usually regarded as futile efforts. Some clinicians and medical ethicists view even the provision of nutrition and hydration as medically futile.