Bilateral polymicrogyria: always think in chromosome 22q11.2 deletion syndromes

Abstract

Polymicrogyria (PMG) is a malformation of cortical development due to an abnormal organisation. It is a heterogeneous disorder associated with genetic and acquired events, namely 22q11.2 deletion syndrome also known as DiGeorge syndrome (DGS) /velocardiofacial syndrome (VCFS) among others. This association has been known since 1996 and more than 30 cases have been described. Neurological features include motor and cognitive impairment, epilepsy, microcephaly and spasticity. The authors present an 8-month old infant with minor dysmorphic features, microcephaly, global psychomotor retardation and epilepsy. Brain MRI revealed diffuse bilateral PMG. The 22q11.2 deletion was confirmed by fluorescent in situ hybridisation (FISH). The child had no other manifestation of DGS/VCFS. paediatricians, neuropaediatricians, development specialists and geneticists should be aware that in the presence of PMG, especially when bilateral, 22q11.2 deletion should be investigated, even in the absence of the typical features of DGS/VCFS. On the other hand, in children with 22q11.2 deletion, brain malformations should be ruled out.

Epilepsy and Other Neuropsychiatric Manifestations in Children and Adolescents with 22q11.2 Deletion Syndrome

“… 4 6 7 Among the detected structural abnormalities, malformations of cortical development including polymicrogyria, focal cortical dysplasia, and subependymal heterotopia appeared relatively frequently in the current patient series, as found in previous studies. 13 14 There are several recent reports of microdysgenesis of the brain in genetic generalized epilepsy or juvenile myoclonic epilepsy. 25 26 As indicated above, epilepsy that arises in 22q11.2DS is closely associated with genetic generalized epilepsy, suggesting the presence of microscopic morphological changes in the brain.…”

“… 27 Furthermore, the present study also demonstrated other rare congenital brain anomalies related to the syndrome such as an anomaly of the cerebral vasculature like hypoplasia of the intracranial artery 21 and a Chiari malformation. 28 Various imaging and histopathological findings in 22q11.2DS have been attributed to a direct effect of the chromosomal microdeletion, 14 21 22 23 and active surveillance for brain malformations can help patients with 22q11.2DS and NP manifestations. The disrupted expression of multiple genes involved in the development and maturation of neurons, neurotransmission, and neuronal circuits 4 5 can explain the broad spectrum of structural abnormalities, epilepsy, and the coexistence of several NP manifestations in 22q11.2DS.…”

“…The disproportionate associations between 22q11.2DS and generalized epilepsy or juvenile myoclonic epilepsy 11 12 suggest that this microdeletion plays a role in genetic generalized epilepsy. Moreover, polymicrogyria and other malformations of cortical development, 13 14 which are major causes of epilepsy, are relatively common in 22q11.2DS. 7 15 16 However, the role of 22q11.2DS in epilepsy and brain development is still unclear.…”

Ictus emeticus presenting as an unusual seizure type in chromosome 22q11.2 deletion syndrome

“…Although MRI indicated cortical malformation in the right hemisphere of our patient, interictal FDG-PET revealed bilateral hypometabolism. This possibly indicated bilateral PMG, which is indicative of brain malformation in patients with 22q11.2DS (Castro et al, 2011).…”