* Department of Gynecology, Felix Guyon Hospital, 97400 Saint- Denis, Reunion Islands, France; tel.: 0262 90 55 22; fax: 0262 90 77 30;
** Diagnostic medical sonographer, editor, translator, Novato, CA. Email: timbre440@yahoo.com;
*** Gynecologist, Jeanne D"Arc clinic, 97400 Le Port, Ile de la Réunion, France;
**** Department of Neonatology, Hôpital Félix Guyon, 97400Saint-Denis, Ile de la Réunion, France;
***** Department of Obstetrics, Hôpital intercommunal de Saint Benoît, Ile de la réunion, France.

Definition

The word microcephaly is used to indicate a heterogeneous group of conditions that share small brain size as established by head perimeter. Microcephaly is defined as head perimeter which is more than two (or three) standard deviations below the mean. Primary microcephaly is a heterogeneous group of cerebral malformations divided in two groups: primary cerebral malformation; or exposure to teratogens.

Microcephaly is most often discovered postnatally. We describe prenatal discovery of microcephaly with an abnormal gyral pattern.

Case report

The patient, G1P0, 20 years old, was referred for targeted examination at 24 weeks because of small fetal head size detected at 24 weeks on sonography. The pregnancy was marked by gradual decrease of cerebral biometry during the second trimester. Borderline values of head perimeter and biparietal diameter were demonstrated. There was no fetal akinesia (such as joint limitations or chest deformity); however, the facial profile was abnormal. The fetus was in vertex lie. Endovaginal sonography was performed. The earlier impression of a disproportionately large subarachnoid space overlying the frontal area was confirmed. The lateral ventricles appeared normal. The frontal lobe was hypoplastic and there was a slanting forehead. Cerebellar size and configuration were normal. The corpus callosum and the anterior cerebral arteries appeared normal. There was enlargement of the arachnoid spaces surrounding the hemispheres. The eyes appeared normal, as did the ears.

Prenatal MRI performed at 26 weeks showed major microcephaly, with hypoplasia of the corpus callosum and enlarged subdural spaces. There was brain hypoplasia and diffuse cortical atrophy, with an abnormal gyral pattern. The patient refused a second MRI at 30 weeks.

Bearing in mind the poor prognosis, termination of pregnancy was proposed and accepted by the parents. A male fetus was delivered at 31 weeks showing microcephaly with external anomalies. Histological examination of the brain was not agreed to by the parents.  Fetal karyotype was normal and TORCH and Chikungunya screen on the mother were normal as well.

Images 1, 2: 24 weeks of gestation; 2D ultrasonography; parasagittal planes through the fetal skull showing microcephaly with large subarachnoid space.

Images 3, 4: 24 weeks of gestation; 2D ultrasonography; parasagittal planes through the fetal skull showing microcephaly with large subarachnoid space.

Images 5, 6: 24 weeks of gestation; coronal (left image) and sagittal (right image) planes of the fetal skull showing normal transcerebellar diameter (left image); and slanting forehead (right image).

Images 7, 8: MRI at 26th week demonstrating microcephaly with smooth cerebral hemispheres and large subarachnoid space (transverse plane - left image; and coronal plane - right image).

Images 9, 10: MRI at 26th week demonstrating microcephaly with smooth cerebral hemispheres and large subarachnoid space (sagittal plane - left image; and coronal plane - right image).

Prevalence

The precise incidence of microcephaly  is unknown, perhaps nearly 2.5:10,000. Frequency is higher in countries with there is greater consanguinity rates. According to Pili et al, microcephaly has an estimated incidence of 1.17:10,000 to 1.6:10,000 neonates. A large proportion of cases has an autosomal recessive inheritance; however, other modes of genetic inheritance can occur. When it is familial, primary microcephaly often appears to be transmitted as an autosomal recessive disorder with an incidence of 0.2:10,000 to 0.33:10,000.

Etiology

The list of causes of microcephaly is very long, but each cause is very rare. Pathological microcephaly usually results from:

• Primary (congenital) brain dysgenesis: this may be the result of a developmental field defect or a genetic abnormality.

  • A genetic syndrome (such a as Cri-du-Chat syndrome, Seckels" syndrome,  Meckel-Gruber syndrome, Rubinstein-Taiby syndrome or Smith-Lemli-Opitz syndrome); Cornelia de Lange syndrome, etc…

  • Chromosomal etiologies (24% of cases), such as T21, T13, T18 4p- syndrome.

• Secondary (acquired) brain dysgenesis: the result of an insult to a normal brain by a

  • Vascular accident (ischemia or hypoxia);

  • Teratogen exposure;  infections (such as Toxoplasmosis, Rubeola, CMV, Herpes); 

  • Multifactorial etiology such as fetal alcohol syndrome; or uncontrolled maternal phenylketonuria (PKU), which is very rare.

  • Methylmercury poisoning.

  • Maternal drug abuse.

Primary microcephaly seems to result from of abnormal proliferation of neural and glial precursor cells, sometimes associated with defective neuroblastic migration and abnormal cortical organization. This is designated as "true " or primary microcephaly.

Following the birth of an affected child, a recurrence rate of 10% is usually given in the absence of any definitive etiological factor. It is estimated that 20 to 35 % of idiopathic cases of microcephaly are hereditary.

Classification

Classification of different forms of microcephaly is complex. Dobyns and Barkovich proposed two groups:

• A group with a relatively well-preserved gyral pattern: This group includes autosomal recessive primary microcephaly. It is true microcephaly, microcephaly vera.

• Several groups with an abnormal gyral pattern: microcephaly associated with simplified gyral pattern, lissencephaly, microlissencephaly, agyria, pachygyria, polymicrogyria or some cortical dysplasias. Our case belongs to this group of microcephaly.

Sonographic findings

Microcephaly is frequently diagnose at the end of the pregnancy or during antenatal first weeks. Obstetric sonographers are rarely faced with the problems of diagnosing fetal microcephaly. Microcephaly is found in the following circumstances: When targeted sonography is performed on a patient at increased risk due to genetic predisposition or exposure to teratogens; or when a fetus with microcephaly is found unexpectedly on routine screening.

Implications for targeted examinations

Amniocentesis should be performed in cases of microcephaly, to ascertain karyotype and DNA. Cerebral MRI is recommended to investigate white-matter disease and anomalies of gyration.

Differential diagnosis

There is no differential diagnosis for microcephaly. It is necessary and important to know the exact date of conception. Microcephaly should not be confused with dolichocephaly when performing biometric measurements.

Associated anomalies

Complete structural fetal evaluation by sonography is essential. Particular attention must be paid to the integrity of the posterior spinal elements, as well as to rule out any problem of growth retardation or placental insufficiency.

All patients with microcephaly who survive the neonatal period will suffer developmental delays, intellectual disability, and often neurological deficits. They often present with epilepsy. Familial microcephaly is usually associated with moderate to severe mental retardation, dependent upon the underlying disorder. After diagnosis of microcephaly is confirmed by MRI, an interruption of pregnancy can be suggested. There is no treatment for microcephaly.