Holoprosencephaly

A disorder characterized by the failure of the prosencephalon (the forebrain of the embryo) to develop. During normal development, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of pregnancy. Holoprosencephaly is caused by a failure of the embryo's forebrain to divide to form bilateral cerebral hemispheres (the left and right halves of the brain), causing defects in the development of the face and in brain structure and function. There are three classifications of holoprosencephaly. Alobar holoprosencephaly, the most serious form in which the brain fails to separate, is usually associated with severe facial anomalies. Semilobar holoprosencephaly, in which the brain's hemispheres have a slight tendency to separate, is an intermediate form of the disease. Lobar holoprosencephaly, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly, the patient's brain may be nearly normal. Holoprosencephaly, once called arhinencephaly, consists of a spectrum of defects or malformations of the brain and face. At the most severe end of this spectrum are cases involving serious malformations of the brain, malformations so severe that they are incompatible with life and often cause spontaneous intrauterine death. At the other end of the spectrum are individuals with facial defects - which may affect the eyes, nose, and upper lip - and normal or near-normal brain development. Seizures and mental retardation may occur. The most severe of the facial defects (or anomalies) is cyclopia, an abnormality characterized by the development of a single eye, located in the area normally occupied by the root of the nose, and a missing nose or a nose in the form of a proboscis (a tubular appendage) located above the eye. Ethmocephaly is the least common facial anomaly. It consists of a proboscis separating narrow-set eyes with an absent nose and microphthalmia (abnormal smallness of one or both eyes). Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes. The least severe in the spectrum of facial anomalies is the median cleft lip, also called premaxillary agenesis. Approximately one-half of all cases of holoprosencephaly have a chromosomal cause. Trisomy 13 (Patau) syndrome and trisomy 18 (Edwards) syndrome are associated with holoprosencephaly. There is an increased risk for holoprosencephaly in infants born to diabetic mothers. There is no treatment for holoprosencephaly and the prognosis for individuals with the disorder is poor. Most of those who survive show no significant developmental gains. For children who survive, treatment is symptomatic.

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Presence of a single forebrain hemisphere or lobe; cycloplia occurs in the severest form. It is often accompanied by a deficit in median facial development. [holo- + G. proso, forward, + enkephalos, brain]

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holo·pros·en·ceph·a·ly (hōl″o-pros″ən-sefґə-le) [holo- + prosencephalon] failure of cleavage of the prosencephalon resulting in incomplete or absent cortical separation and deficits in midline facial development; usually subdivided into alobar, semilobar, and lobar forms on the basis of degree of lobar separation. Facial dysmorphisms may include cyclopia, micro- or macrocephaly, micro- or anophthalmia, hypo- or hypertelorism, single nostril, and cleft lip or palate. It has a variety of causes, including chromosomal and single-gene disorders and environmental factors, and may occur alone or associated with various syndromes. Nonsyndromic familial forms show genetic heterogeneity, variable expressivity, and variable penetrance; mutations in the Sonic Hedgehog (SHH) gene are a major cause of the nonsyndromic autosomal dominant form.

Lobar holoprosencephaly. MRI scan demonstrates failure of separation of the hemispheres and a persistent fused ventricle.