Septopreoptic Holoprosencephaly: A Mild Subtype Associated with Midline Craniofacial Anomalies

Abstract

SUMMARY: HPE is a congenital brain malformation characterized by failure of the prosencephalon to divide into 2 hemispheres. We have identified 7 patients who have a mild subtype of HPE in which the midline fusion was restricted to the septal region or preoptic region of the telencephalon. This subtype, which we call septopreoptic HPE, falls in the spectrum of lobar HPE, but lacks significant frontal neocortical fusion seen in lobar HPE. Other imaging characteristics include thickened or dysplastic fornix, absent or hypoplastic anterior CC, and single unpaired ACA. The SP was fully formed in 4, partially formed in 2, and absent in 1. Mild midline craniofacial malformation, such as SMMCI and CNPAS were found in 86% and 71%, respectively. Patients outside of infancy often manifested language delay, learning disabilities, or behavioral disturbances, while motor function was relatively spared.ABBREVIATIONS: AC ϭ anterior commissure; ACA ϭ anterior cerebral artery; CC ϭ corpus callosum; CNPAS ϭ congenital nasal piriform aperture stenosis; FSPGR ϭ fast-spoiled gradient-recalled; HPE ϭ holoprosencephaly; IHF ϭ interhemispheric fissure; MPR ϭ multiplanar reconstructed; SMMCI ϭ single median maxillary central incisor; SP ϭ septum pellucidum; SPGR ϭ spoiled gradient-recalled; V3 ϭ third ventricle H PE is a complex congenital brain malformation characterized by failure of the forebrain to bifurcate into 2 hemispheres, a process normally complete by the fifth week of gestation.1 As the name "HPE" implies, these nonseparated prosencephalic structures involve parts of the telencephalon and diencephalon. HPE has traditionally been classified according to DeMyer's 3 grades of severity: alobar, semilobar, and lobar.2 In addition to these classic forms, a subtype of HPE, the middle interhemispheric variant or syntelencephaly, has been characterized. 3,4 In these types of HPE, there is significant nonseparation of the neocortex of the cerebral hemispheres. In the alobar type, the entire hemispheres are involved, and in the semilobar and lobar types, the frontal lobes are primarily involved. In the middle interhemispheric variant, there is nonseparation of the posterior frontal and anterior parietal lobes in the perirolandic region. We report a series of patients who have a very mild form of HPE, in which the nonseparation is restricted to the septal (subcallosal) and/or preoptic regions or both regions (Fig 1). Patients with this type of HPE often present initially with mild midline craniofacial malformations, including SMMCI and CNPAS. Our aim was to characterize the neuroimaging and clinical findings of a mild subtype of HPE that has less neocortical fusion than classic lobar HPE. Materials and MethodsWe searched the neuroimaging data base of the Carter Centers for Research in Holoprosencephaly and Related Malformations for patients who met the criterion for a mild subtype that we call "septopreoptic HPE." The imaging criterion for inclusion was abnormal fusion restricted to the septal (subcallosal) and preoptic telencephalic re...

Corpus Callosal Abnormalities in Dogs

“…By definition, these dogs therefore had a mild subtype of lobar holoprosencephaly 22. Recently, a very mild form of holoprosencephaly (HPE) has been reported in people by Hahn;23 in this subtype, named septopreoptic HPE, the nonseparation is restricted to the septal (subcallosal), preoptic regions, or both. In all cases, the CC was abnormally formed, with aplasia or hypoplasia of the rostrum and less severe hypoplasia of the genu.…”

Genotypic and phenotypic analysis of 396 individuals with mutations inSonic Hedgehog

“…HPE is categorised neuroanatomically by the degree of forebrain separation into alobar (the most severe type), semilobar, lobar, middle interhemispheric variant, and septopreoptic types 9 . SHH mutation ‘carriers’ have been described as clinically unaffected by severe sequelae of disease, and are frequently referred to as having ‘microform’ HPE.…”

Lobar Holoprosencephaly: Cranial Sonography and MRI Imaging Features

“…Common MR imaging features in case of lobar holoproscencephaly are absence of septum pellucidum, well formed interhemispheric fissure, unfused basal ganglia & thalami, fused anterior horns of lateral ventricles and dysplastic corpus callosum [14]. Azygous ACA can be found on MRI [15]. Additional fused cingulated gyrus is noted on MR imaging of brain.…”