holoprosencephaly ( hpe ) is a type of central nervous system malformation resulting from hypoplasia or aplasia of the most rostral end of the neural tube and premaxillary segment of the face . it is characterized by varying degrees of incomplete separation of the cerebral hemispheres and deep brain structures such as basal ganglia , thalamus , and hypothalamus . based on the severity of involvement , three categories have been described , namely alobar , semilobar , and lobar hpe . a fourth type of hpe , namely middle interhemispheric variant ( mih ) or syntelencephaly has been described , which is characterized by deficient interhemispheric fissure involving the high frontal convexity with normal interhemispheric separation of basal forebrain , anterior frontal and occipital lobes . a 5-year - old girl presented to our institute with poor mental and motor development . born by normal vaginal delivery at term , she had cried at birth and the neonatal period was uneventful . there was no history of in - utero exposure to infections , drugs , or radiation . there was no family history of brain malformations , developmental delays , facial abnormalities , or chromosomal abnormalities . on examination , the child had only partial neck control , reached for objects with immature grasp , could recognize only family members and vocalized meaningless vowel sounds . the child weighed 13.5 kg ( <3 percentile ) with a head circumference of 48 cm ( 515 percentile ) . dysmorphic facial features such as metopic prominence , bushy eyebrows with synophrys , broad nasal root , flat nasal bridge , telecanthus , and shallow philtrum were seen [ figure 1 ] . neurological examination revealed normal cranial nerves , bilaterally symmetrical muscle bulk with increased tone in all the limbs , and generalized hyperreflexia . ( a ) frontal view shows metopic prominence , bushy eyebrows with synophrys , broad nasal root , telecanthus , and shallow philtrum , ( b ) lateral view shows metopic prominence with flat nasal bridge on magnetic resonance imaging ( mri ) , deficient interhemispheric fissure was observed in posterior frontal and parietal regions with failure of separation of posterior frontal and parietal lobes . the anterior and posterior parts of the interhemispheric fissure were normally formed . sylvian fissures showed abnormal vertical orientation and were fused across midline over the vertex of brain . genu and splenium of corpus callosum were normally formed , and the body was absent in the region of interhemispheric connection . ( a ) axial t1-weighted image shows abnormal orientation of sylvian fissures ( arrows ) , which are connected across the midline and nonseparation of posterior frontal and parietal lobes ( arrowheads ) , ( b ) axial t2-weighted image at the level of basal ganglia shows normal separation of basal and anterior frontal lobes and occipital lobes . the frontal horns are hypoplastic with absent septum pellucidum , ( c ) sagittal t2-weighted image shows agenesis of body of corpus callosum ( arrows ) with normal splenium and genu , ( d ) parasagittal t2-weighted image shows vertical orientation of sylvian fissure ( arrows ) and vertical course of middle cerebral artery ( arrowhead ) the embryonic neural tube differentiates into various regions of brain parenchyma by means of ventral and dorsal patterning , which are induced by specialized cell groups in the neural tube . such cell groups form the floor plate in the ventral potion and roof plate in the dorsal portion of neural tube . mih has been postulated to result from a defect in the induction of embryonic roof plate unlike the classic types of hpe , which result from a defect in the induction of embryonic floor plate . mih is characterized by deficient interhemispheric fissure with failure of separation of posterior frontal and parietal lobes despite normal separation of anterior and posterior portions of the cerebral hemispheres . the basal ganglia structures are usually separated with variable fusion of thalami noted in 3050% of cases . sylvian fissures are characteristically oriented vertically and are connected across the midline over the vertex . the body of the corpus callosum is usually deficient in the region of interhemispheric nonseparation , whereas the genu and splenium are normally formed . other common associations include cortical dysplasias , heterotopias , azygos cerebral artery , and a dorsal interhemispheric cyst . in contrast , semilobar and lobar types of hpe are characterized by defective separation of anterior and rostral parts of the frontal lobes with normal interhemispheric cleavage posteriorly . variable degrees of fusion of basal ganglia are noted in both these conditions , whereas the thalami are separated in lobar and variably fused in semilobar type . in both these entities , the incidence of craniofacial anomalies is less severe and less frequent in mih , when compared with the classic types of hpe . endocrinopathies and choreoathetosis , which are commonly observed in other forms of hpe are relatively rare in syntelencephaly due to lack of involvement of basal forebrain structures . despite these differences in the clinical presentation and imaging findings , mih variant shares a common denominator with the classic forms of hpe in that there is nonseparation of a part of the supra - tentorial brain into two separate hemispheres . mutations involving the zic2 gene , located on human chromosome 13q32 , has been postulated in the pathogenesis of hpe and syntelencephaly . it is expressed in the dorsal and ventral midline regions of the telencephalon unlike other genes identified in hpe , which are expressed predominantly in the ventral regions . in a study of 509 individuals with various types of hpe , mutations of the zic2 gene was observed in 16 cases . fifteen of them had alobar , semilobar , or lobar hpe ; and in the remaining one who had the mih variant , a comparatively mild mutation of the zic2 gene ( in - frame deletion of 12 amino acids ) was observed . it was suggested that the level of function of the protein determined the severity of hpe ranging from alobar to mih variant , which in turn was dependent on the severity of mutation of the gene . the mih variant of hpe or syntelencephaly has characteristic imaging findings and radiologists are often the first to diagnose this condition . familiarity with these findings can help in early diagnosis and prognostication of the affected children .