Prenatal diagnosis, management and prognosis of malformations of cortical development: a multicentre study

Malformations of cortical development (MCD) are rare congenital brain disorders and no curative therapy exists. We report a case series (retrospective and prospective) to better characterise them. We collected 26 cases of MCD from our database (1999-2020). Inclusion criteria were: availability of cerebral imaging, genetic analysis and neurologic outcome at two years old. The syndromic associations and congenital infections were excluded. Prenatal ultrasound (US) found cerebral alterations in 19 cases, at an average gestational week of 23. Common features were microcephaly or megalencephaly, bilateral and severe ventriculomegaly and corpus callosum anomalies. Fetal magnetic resonance imaging (fMRI) was performed on 16 cases. It demonstrated polymicrogyrias (n:3), retardations of gyration (n:2), simplified gyration (n:2), dysplasias (n:6), lissencephalies (n:6) and heterotopies(n:1). Prenatal and postnatal MRI findings were concordant. Seven cases were diagnosed postnatally between one and four years old (1 lissencephaly, 5 microcephaly and 1 megalencephaly). Genetic diagnosis was possible in 16 cases: eleven using next generation sequencing (NGS), eight with clinical exome. CGH array was never conclusive. Nine cases were diagnosed between 2018 and 2020 by NGS. Thirteen pregnancies were interrupted (TOP) at an average gestational week of 29. Only one infant has normal neurological development (three years old, postnatal microcephaly). The majority has several neurological impairments.