Synonyms: Exencephaly.

Prevalence: About 20 cases diagnosed prenatally.

Definitions: Acrania is a developmental abnormality characterized by a partial or complete absence of calvarium, with complete but abnormal development of brain tissue^{1, 2}. Meroacrania refers to absence of the cranium with the exception of the occipital bone. Meroanencephaly is a form of anencephaly with rudimentary brain and cranium.

Etiology: 1) A failure of the migration of the ectodermal mesen­chyme or 2) a disruption by amniotic bands.

Pathogenesis: Anomaly of the ectodermal-derived structures of the cranium (skull, skin, dura) with improper induction of the brain morphology.

Associated anomalies: See table 2.

Differential diagnosis: Anence­phaly, cephalocele, hypophospha­tasia, osteogenesis imperfecta (Type II).

Prognosis: Uniformly fatal.

Recurrence risk: Not known to be increased, and in particular, not known to increase the risk of neural tube defect.

Management: As for diseases with fatal outcome.

MESH Brain-abnormalities ICD9 740.0 CDC 740.010

* Address correspondence to Tae-Hee Kwon, MD, Visiting Fellow, Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, 21^st and Garland Ave, Nashville, TN 37232-2675. Ph 615-322-0999 Fax 615-322-3764

Introduction

Acrania is a developmental anomaly characterized by partial or complete absence of the neurocranium, with complete but abnormal development of brain tissue¹. This rare lethal congenital anomaly has important implications for obstetrical management and counselling. Ultrasound allows early diagnosis of this anomaly.

We report our experience with 13 fetuses detected prenatally by sonography as having  acrania or meroacrania, and the differential diagnosis with anencephaly and cephaloceles.

Materials and methods

Thirteen cases of acrania were collected from October 1985 to January 1991 at Vanderbilt University Medial Center. Fetuses were scanned for a variety of reasons such as dating, size-to-date discrepancy, increased alpha-fetoprotein, maternal diabetes mellitus (1) and  medication (2) (one asthma, one cough). The gestational age ranged from 17 to 32 weeks at the time of initial diagnosis. Scans were performed with either a Toshiba SAL 77A, 100, or 270 (Toshiba America Medical Systems, Tustin, CA) using either a 3.75-MHz or 5-MHz curvilinear array transducer, depending on the patient"s body habitus.

A limited autopsy was obtained in five cases, and a complete autopsy in another two cases. Fetal karyotyping was performed in six cases using amniotic fluid, blood, skin or lung tissue of  fetus (post delivery).

Results

The diagnosis of acrania was established by the following criteria: normal facial bone and a normal cervical column without fetal skull and a volume of brain tissue at least equivalent to a third of the expected size of the brain (fig. 1). When the brain was present but the amount appeared small, the lesion could represent meroacrania or meroanencephaly. Only when no brain or only a small brain tag was seen, was the lesion referred to as anencephaly and not include in this study.

Fig. 1: Top: Acrania with a large amount of brain tissue. Bottom:  in this case a volume of brain, about half the normal size is seen “hanging” to the side of the head.

Table 1 summarizes the sono­graphic, pathologic, and historic findings of each of the 13 cases.

Table 1: History, findings and outcome in this series

(*) Age: first line: maternal age in years, second line: gestational age in weeks

The mean maternal age was 24 years (range 18-33). Of the 13 affected pregnancies, 12 were singleton and one was a twin pregnancy, in which only one of the two fetuses had acrania. Only 1 case had alpha-fetoprotein determination. Aside from acrania, seven fetuses had associated anomalies (see table 2).

Table 2: Associated anomalies in this series (*) and in the literature^{1-2, 6-7}.

CNS & spine

• Lipoma of the cord*

Face & neck

• Cleft lip - palate*
• Hypo- and hypertelorism*
• Exophoria*

Cardiovascular:

• Atrial septal defect*
• Ventricular septal defect*
• Transposition of the great vessels*

Gastrointestinal

• Omphalocele*

Genitourinary

• 2 vessel cord*

Musculoskeletal

• Club foot*

Placental, cord & membranes

• Amniotic bands*
• Oligohydramnios*
• Polyhydramnios*

Other

• Increased a-fetoprotein*

The twin pregnancy delivered prematurely at 32 weeks due to premature rupture of the membranes. Fetal karyotype studies were performed in 6 cases using amniotic fluid, blood, skin or lung tissue of fetus. All karyotypes demonstrated normal 46 XX .

All affected fetuses died (pregnancy termination: 6, after delivery: 7). Complete autopsies were carried out in two cases, with limited autopsies obtained in five additional cases. The prenatal diagnosis was confirmed in each cases.

At autopsy the fetal heads were characterized  by absence of scalp, skull, and dura from the browline cephalad. The brain was covered by a layer of leptomeninges which was brown-red in color and relatively thickened. The eyes had a pronounced prominence.

A false diagnosis of anencephaly may be made at autopsy if the brain is not protected. Because of the soft consistency of the brain, it is easy to separate from the skull and it may not be forwarded to pathology as the fetus is changed from one set of sheets onto another. In our hospital for instance, the fetus is usually presented to the mother and photographs are made to give to the mother (for initiation of the grieving mechanism). To render the fetus more attractive, the cranial defect is hidden by a small fabric “hat”. When the fetus is then transferred, the “hat” is discarded in Labor and Delivery.

Discussion

Incidence

Although acrania associated with anencephaly is a well recognized entity with an incidence of about 10:10,000 births, isolated acrania is a rare anomaly, and its incidence is unknown. Very few cases (less than 20) have been reported in the world literature^{1, 3-4}. Six of our seven fetuses in which the sex was reported were females and one male.

Definitions

The bones of the skull are divided in two parts: the viscerocranium (the skeleton of the face) and the neurocranium, itself composed of the chondrocranium which forms the bones of the base and the membranous flat bones which encase the brain. Acrania affects the membranous flat bones and it is not uncommon to see rudimentory bones at the base of the skull.

Etiology

Acrania may result from two different mechanisms: 1) a disruption by amniotic bands or 2) a failure of the migration of the ectodermal mesenchyme (fig. 2). The second mechanism results from an embryological maldevelopment which can be easily understood even though the etiology remains unclear⁵.

Fig. 2: Top: Acrania from failure of migration of the ectodermal mesenchyme. Bottomt: Acrania from amniotic band disruption.

Embryology

Acrania occurs during the beginning of the fourth week of development when the anterior neuropore closes. The desmocranium (the mesenchymal primordium overlying the future cerebral hemisphere) which normally becomes the epidermis of the scalp, remains a membranous coverage. The normal migration of mesenchymal tissue under the calvarium ectoderm does not occur. Thus, the calvarial dermal bones of the skull, related musculature, and dura mater are absent. However, the cartilaginous skull bones form a normal skull base and foramen magnum. Philogenetically the origin of the viscerocranium and chondrocranium corresponds to the support used in the fishes. The considerable enlargement of the brain resulted in a herniation through these primitive cartilaginous bones. The protection of the growing brain could not be achieved by theses bones, and instead was provided by differentiation of the overlying skin into membranous bones. The development of the neurocranium is necessary to induce the formation of the brain. In its absence, the cerebral tissue fails to differentiate into  two hemispheres. The cerebellum, brainstem and cranial nerves are normal, but the growth of the diencephalon, and ocular globe is abnormally small¹.

Prenatal diagnosis

The condition is identified by the absence of the calvarium. The cerebral hemispheres are surrounded by a thin membrane. The demonstration of abundant, albeit abnormal brain tissue on the sonogram helps differentiate cases of acrania from the more common anencephaly. Acrania and meroacrania may not be neural tube defects and should be differentiated from anencephaly.

The prenatal diagnosis and intrauterine monitoring of acrania are possible with ultrasound during pregnancy. The biochemical and cytological examination of amniotic fluid samples may suggest the presence of a neural tube defect, but a specific prenatal diagnosis of acrania is only possible by ultrasound scanning.

Associated anomalies

The associated anomalies seen in our cases of acrania are listed in Table 2. Similar pathologic findings have been described in the amniotic band syndrome². Only two of our cases were due to amniotic bands.

Differential diagnosis

The differential diagnosis includes anencephaly and large cephaloceles. In anencephaly, cerebral tissue is completely absent; while in cephaloceles, the cranial vault can always be detected and a part of the brain is intracranial. A distinction should also be made between acrania and conditions characterized by lack of mineralization of the skull bones such as hypophosphatasis and osteogenesis imperfecta Type II. In these  skeletal dysplasias, the intracranial anatomy is normal, and the brain is surrounded by a thick layer of tissue representing soft tissues and unossified bone. Bowing, fractures or shortening of long bones are usually present.

Prognosis & management

Acrania is uniformly lethal². Antenatal identification allows the clinician to make appropriate and timely management decisions.

References

1. Mannes EJ, Crelin ES, Hobbins JC, et al: Sonographic demonstration of fetal acrania. AJR 139: 181, 1982.

2.Romero R, Pilu G, Jeanty J, et al. Prenatal Diagnosis of Congenital Anomalies. Appleton & Lange, Norwalk, Connecticut, 1988. pp 75-76.

3. Kristoffersen K, Pedersen BN, Secher NJ, et al: Akrani og spina bifida diagnosticeret ved bestemmelse af alfa fotoprotein: 16. graviditesuge. Ugeskr Laeger 137: 1719,1975.

4. Vergani P, Ghidini A, Sirtori M, et al: antenatal diagnosis of fetal acrania. J Ultrasound Med 6: 715-717, 1987.

5. Moore KL: The Developing Human, 3rd ed. Philadelphia, W.B. Saunders, 1982, pp351-354.

6. Frezal J, Kelly J, Guillemot ML et al.: Anencephaly in France. Am J Hum Genet 16: 336,1964.

7. Giround A: Anencephaly. In: Vinken GW, Bruyn PW (des): Handbook of clinical neurology. Amsterdam, Elsevier/ North Holland Biochemical Press, 1977, Vol 30, pp 173-208.