Paediatric neuro-imaging: diagnosis.
Imaging and findings
A 2-year-old boy presented with microcephaly and developmental delay. The MRI images referred to above, were obtained.
The sagittal T1 (Fig. 1) sequence shows an abnormal appearance of the corpus callosum. The entire body of the corpus callosum is remarkably thin. Only the splenium and part of the genu is relatively spared. Along with the posterior frontal and parietal lobe cerebral fusion, note the absence of the septum pellucidum and fused frontal horns of the lateral ventricles (Figs 2 - 4). The sylvian fissures appear continuous across the hemispheres. MRA of the intracranial vessels (Fig. 5) demonstrates an azygous anterior cerebral artery. The combination of features is compatible with a syntelencephaly subtype of holoprosencephaly.
Holoprosencephaly (HPE) is perhaps one of the more complex and captivating congenital brain malformations, with its striking imaging phenotype abnormalities and complex neurological impairment. It is characterised by failure of cleavage of the prosencephalon, a process that usually occurs between the 18th and 28th days of gestation. The overall incidence is much higher than expected, with up to 1 in 250 conceptions affected. With the immense improvement in neuro-imaging, particularly in magnetic resonance imaging, we are now able to delineate the specific areas of involvement including cerebral frontal and parietal lobes, basal ganglia, thalami, orbits and facial structures. There are four subtypes of this malformation. The spectrum includes the classic HPE subtypes in the De Myer classification (viz. alobar, semilobar and lobar HPE), in addition to the fourth subtype known as the middle interhemispheric variant of holoprosencephaly (MIH) or syntelencephaly (Table 1). Solitary median maxillary central incisor is one of several microforms of autosomal dominant HPE not usually included in the classification.
Table 1. Subtypes of holoprosencephaly and differentiating features (1), (4), (5) Alobar Semilobar Lobar Degree of Almost complete Posterior Rostral and prosencephalon non-separation cerebral ventral frontal non-separation with holosphere hemispheres lobe fusion. of cerebral near normal. Rest of parenchyma. Fused anterior cerebral aspect with hemispheres undeveloped separated. frontal lobes. Falx cerebri and Absent IH Partial Hypoplastic interhemispheric fissure. Dorsal formation of anterior falx. (IH) fissure cyst present. shallow IH Fissure is fissure and present. falx posteriorly. [+ or -] Dorsal cyst. Falx absent anteriorly. Corpus callosum Agenesis of Genu and Genu mildly abnormality corpus anterior body dysplastic. callosum. absent. Body and Splenium splenium almost well-formed. normal. Severity, Lethal subtype. Intermediate Mild subtype. additional Stillborn or severity. Present later features and short lifespan. Dorsal cyst with visual prognosis Severe facial seen when difficulties or dysmorphism. thalami are developmental Cyclopia. fused. Frontal delay. [+ or -] Olfactory horns absent. Mild olfactory aplasia. Occipital bulb and tract Monoventricle. horns normal. hypogenesis. MIH Degree of Posterior prosencephalon frontal and non-separation parietal lobe fusion. Caudate and thalami often incompletely cleaved. Falx cerebri and Anterior falx interhemispheric is normal or (IH) fissure mildly dysplastic. Posterior aspect of falx is absent. Azygous ACA. Corpus callosum Absent body of abnormality corpus callosum with normal splenium and genu. Severity, Mild cognitive additional and vision features and impairment. prognosis Facial features similar to lobar subtype. Best prognosis.
MIH is a relatively milder clinical form of holoprosencephaly, first described in 1993 by Barkovich et al. (1) Although akin to other forms of holoprosencephaly, MIH is thought to develop on a somewhat different pattern of midline non-cleavage. The classic subtypes of HPE all involve induction of the embryonic floor plate, and SHH is the primary gene abnormality described among several others. In contrast, in the pathogenesis of MIH it is the embryonic roof plate that is involved. Mutations of the ZIC2 gene on chromosome 13, which plays a critical role in differentiation of the roof plate of the developing embryo, have been implicated in MIH. (2)
The affected children present with a variety of deficits including spasticity, dystonia and oromotor dysfunction affecting feeding and speech. Seizures as well as mild cognitive and visual impairment are noted in these children. Endocrinopathy is not a common feature owing to sparing of the hypothalamus and basal forebrain. When compared with other forms of HPE, the overall functional levels including mobility, hand/arm function and speech are better in patients with MIH.
On MR imaging, MIH is characterised by abnormal fusion of the posterior frontal and parietal regions of the cerebral hemispheres. The anterior portions of the frontal lobes, olfactory tracts and the occipital lobes are usually normal. There is frequent incomplete cleavage of the heads of the caudate nuclei and thalami, but the hypothalamus and lentiform nuclei are well-separated. Almost all patients with MIH have a single or azygous anterior cerebral artery. There is a coronal configuration of the sylvian fissures which are continuous across the cerebral vertex. Frequent association with heterotopias and malformations of cortical development have been reported. (3)
In the presence of typical MRI features, a reasonably confident diagnosis of syntelencephaly may be made even antenatally. (4) This radiological diagnosis may serve as a valuable tool in prognostication and in the counselling of parents.
S Afr J Rad 2013;17 (2):72-73. DOI:10.7196/SAJR.889
(1.) Barkovich AJ, Quint DJ. Middle interhemispheric fusion: An unusual variant of holoprosencephaly. AJNR 1993;14:431-440.
(2.) Brown L, Odent S, David V, et al. Holoprosencephaly due to mutations in ZIC2: Alanine tract expansion mutations may be caused by parental somatic recombination. Hum Mol Genet 2001;10:791-796.
(3.) Fujimoto S, Togari H, Banno T, Wada Y. Syntelencephaly associated with connected transhemispheric cleft of focal cortical dysplasia. Pediatr Neurol 1999;20:397-389.
(4.) Pulitzer SB, Simon EM, Crombleholme TM, Golden JA. Prenatal MR findings of the Middle Interhemispheric Variant of Holoprosencephaly. AJNR 2004;25:1034-1036.
(5.) Kanekar S, Shively A, Kaneda H. Malformations of ventral induction. Semin Ultrasound CT MRI 2011 32 (3):200-210.
S K Misser, MB ChB, FCRad (D) SA
Lake Smit and Partners, Durban, South Africa
Corresponding author: S K Misser (firstname.lastname@example.org)
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|Title Annotation:||QUIZ CASE|
|Publication:||South African Journal of Radiology|
|Article Type:||Clinical report|
|Date:||Jun 1, 2013|
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