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 .
 middle interhemispheric variant ( mih ) of holoprosencephaly ( hpe ) or syntelencephaly is a rare variant of hpe characterized by abnormal midline union of the posterior frontal and parietal lobes with variable fusion of thalami . 
 it varies from classic hpe in embryopathogenesis , severity of fusion of brain structures , associated craniofacial anomalies and clinical presentation . 
 we report a case of mih in a 5-year - old girl , who presented with severe developmental delay and discuss the features differentiating it from other more common forms of hpe . 
Introduction
Case Report
Discussion
Conclusion
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