pediatrics
Malformed Cerebral Hemispheres
Holoprosencephaly
Holoprosencephaly spectrum occurs when the embryonic prosencephalon (which becomes the forebrain) does not undergo complete segmentation and cleavage. Holoprosencephalies may be caused by mutations in a number of genes, of which > 14 are known; among these are the sonic hedgehog signaling pathway genes and their modifiers ( Holoprosencephaly references ). The 3 main types of holoprosencephaly, in declining order of severity, are Alobar Semilobar Lobar Alobar holoprosencephalyis the most severe and is usually fatal. It is characterized by complete failure of cleavage and a single ventricular cavity without any septation. Semilobar holoprosencephalyis characterized by partial cleavage into hemispheres posteriorly but with a communicating unified ventricular cavity anteriorly. Lobar holoprosencephalyis characterized by absence of the septum pellucidum (the membrane that separates the front of the 2 lateral ventricles), agenesis of the corpus callosum, fusion of the anterior horns of the lateral ventricles, and possibly fusion of the cingulate gyri. A fourth, rare type, called middle interhemispheric variant, is characterized by fusion of the posterior frontal and parietal lobes as well as possibly the thalamus but with normal hemispheric differentiation elsewhere. Rhombencephalosynapsis is a malformation similar to holoprosencephaly but mainly involves the hindbrain ( Holoprosencephaly references ). In rhombencephalosynapsis, there is fusion of the cerebellar hemispheres with partial or complete absence of the vermis (the midline portion of the cerebellum). This malformation can result in aqueductal stenosis and hydrocephalus. Other possible associated abnormalities include forebrain holoprosencephaly, absence of the olfactory bulbs, dysgenesis of the corpus callosum or septum pellucidum, and VACTERL ( Introduction to Congenital Craniofacial and Musculoskeletal Abnormalities are present in the holoprosencephalies, and their degree of severity usually mirrors the underlying brain abnormality. Included in the spectrum are Severely affected fetuses may die before birth. After birth, manifestations include seizures, intellectual disability, low muscle tone, and motor delays that affect all modalities of functioning. Treatment of holoprosencephaly is supportive. 1.Hong M, Srivastava K, Kim S, et al: BOC is a modifier gene in holoprosencephaly.Hum Mutat38(11):1464–1470, 2017. doi: 10.1002/humu.23286 2.Ishak G, Dempsey J, Shaw D, et al: Rhombencephalosynapsis: A hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity.Brain135(5):1370–1386, 2012. doi: 10.1093/brain/aws065 