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KEY POINTS
Holoprosencephaly derives from failed or incomplete cleavage of the prosencephalon and is featured by varying degrees of fusion of the cerebral hemispheres, and has a very severe prognosis in most cases.
It is frequently associated with other anomalies and genetic conditions.
Prenatal sonographic diagnosis of the most severe forms that typically are found with severe craniofacial malformations and is usually straightforward since early gestation.
Lesser degrees of anatomic alteration are associated with more subtle findings that may be difficult to recognize or categorize.
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The ontogenesis of the cerebral midline takes place between the fifth week after conception and midgestation.1 Anomalies occurring during this period lead to the development of a wide range of malformation with a severity that is related not only to the time of occurrence but also to the mutations involved. Cleavage of the prosencephalon is closely related to facial development, and many fetuses and children with prosencephalic disorders suffer from facial anomalies. A categorization of these anomalies is reported in Table 7–1. Disorders of prosencephalic formation, aprosencephaly and atelencephaly, will not be discused here. They are the extreme end of the spectrum of severity and occur rarely. Aprosencephaly is the complete lack of development of the telencephalon and diencephalon, and in atelencephaly, the diencephalon is present but usually abnormal.2 In all prenatal reports, a different brain malformation was diagnosed in utero and the definitive diagnosis was reached only after pathological examination.3 Disorders of prosencephalic cleavage, which include mostly holoprosencephaly, follow in the degree of severity.
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Holoprosencephaly (HPE) is a genetically and phenotypically heterogeneous disorder involving the development of the forebrain and midface.
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There are 1 to 1.7 per 10,000 births and terminations.4,5 The real incidence is probably higher than that, because the most severe forms of HPE may result in early pregnancy loss,6 while minor forms will not be recognized at birth, thus escaping epidemiologic surveys.
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HPE is commonly regarded as the result of a failure of cleavage of the prosencephalon. The prosencephalon is the most rostrad of the three primitive cerebral vesicles and gives rise to the cerebral hemispheres and diencephalic structures (including neurohypophysis, thalami, and third ventricle). This differentiation process is thought to be induced by the precordal mesenchyma, which is probably also responsible for the differentiation of the median facial structures (forehead, nose, interorbital structures, premaxilla, and ...