Hemimegalencephaly: Prenatal Diagnosis and Outcome

Abstract

Hemimegalencephaly (HME) is a developmental abnormality of the central nervous system (CNS) which may present as either a syndromic or isolated case. Here, we present two cases of early prenatal diagnosis of HME. Prenatal CNS ultrasound and MRI in the first case revealed ventricular asymmetry, midline shift with displacement of the occipital lobe across the midline, large dilatation mainly at the posterior horn of the left lateral ventricle, and a head circumference in the 90th percentile without involvement of the brain stem and cerebellum, as well as abdominal lymphangioma. Right hemispherectomy was performed at 3 months of age due to intractable seizures. The pathological specimen showed findings characteristic of HME, including a disorganized cytoarchitecture with lack of neuronal lamination, focal areas of polymicrogyria, and neuronal heterotopias with dysplastic cells. In the second case, 2D and 3D neurosonography demonstrated similar findings (asymmetry of cerebral hemispheres, midline shift, and dilation of the posterior horn of the left lateral cerebral ventricle). Posterior fossa structures were unremarkable. HME was diagnosed and the pregnancy was terminated. Autopsy findings confirmed the diagnosis of HME.

The Diverse Genetic Landscape of Neurodevelopmental Disorders

“…Recently, somatic mutations in the PI3K-AKT-mTOR pathway were identified as causing hemimegalencephaly (71,101,106). Hemimegalencephaly is an overgrowth disorder of one hemisphere of the brain, often causing severe epilepsy that requires resection of the entire hemisphere (3,6,54,113,116). The sporadic nature of the disease and localized brain involvement is consistent with a noninherited pattern and highly suggestive of somatic mutation (9).…”

“…Whether somatic mutations also cause diseases of connectivity without structural abnormalities, including neuropsychiatric diseases and ASDs, where de novo mutations are common, remains unanswered. For focal malformations, tissue resection is often necessary to control epilepsy (3,6,54,113,116) and provides a means for postoperative diagnostic confirmation. In hemimegalencephaly patients with other nonbrain malformations, low levels of mosaicism were detected in blood and saliva samples (106), suggesting that in cases where somatic mutations occur early during embryogenesis and affect multiple organ systems, noninvasive diagnosis is possible.…”

Imaging evaluation of fetal vascular anomalies

“…However the fetal MRI characterized the brain findings as hemimegalencephaly, a rare disorder that has been described in isolation or in association with these vascular malformations [21,22]. The reported findings include macrocephaly, asymmetrical enlargement of one cerebral hemisphere, ipsilateral ventriculomegaly and gyral disorganization [23]. A particularly challenging case in our series was a very large venous-lymphatic malformation with a predominantly venous component (case 8) that presented with a high-flow vascular pattern, increased combined cardiac output and cardiomegaly.…”

Prenatal-postnatal correlations of brain abnormalities: How lesions and diagnoses change over time

“…In the few cases where it was diagnosed prenatally, the diagnosis was suggested by routine second trimester ultrasound but only confirmed with fetal MR or 3D ultrasound. Ultrasound features indicating the diagnosis in a recent case series of two patients included asymmetry of the cerebral hemispheres and/or lateral ventricles, macrocephaly, displacement of the occipital lobe across the midline and asymmetric dilation of the occipital horn of the contralateral ventricle [28]. MRI typically reveals an overall increased size of the cerebral hemisphere, abnormal gyration, and VM [32].…”

“…Hemimegalencephaly also may be difficult to diagnosis early in pregnancy ( Fig. 8) and prenatal diagnosis of this condition has only been recently reported [28][29][30][31]. In the few cases where it was diagnosed prenatally, the diagnosis was suggested by routine second trimester ultrasound but only confirmed with fetal MR or 3D ultrasound.…”