Classification of Malformations of Cortical Development

Table 1. Overview of Classification

I. Malformations due to abnormal neuronal and glial proliferation or induction
    A Generalized/diffuse
    B. Focal or multifocal
II. Malformations due to abnormal neuronal migration         
    A Generalized/diffuse
    B. Focal or multifocal
Ill. Malformations due to abnormal cortical organization
    A Generalized/diffuse
    B. Focal or multifocal
IV. Malformations of cortical development. NOC

Table 2 Detailed Classification

I. Malformations due to neuronal & glial proliferation
    A Generalized
        1.Decreased
            a. Extreme microcephaly with simplified gyral pattern (MSG)
                1. MSG group 1 (normal neonatal course, mild spasticity no seizures normal myelination)
                2. MSG group 2 (abnormal neonatal course, severe spasticity, neonatal seizures, delayed myelination)
                3. MSG group 3 (abnormal neonatal course, severe spasticity, myoclonic seizures, normal myelination, heterotopia)
                4. MSG group 4a (jejunal atresia, severe spasticity, myoclonic seizures normal myelination)
                5. MSG group 4b (arthrogryposis, severe spasticity, neonatal seizures normal myelination)
            b. Microlissencephaly (MLIS)
                1. MLIS with thin cortex, no other anomalies
                2. MLIS with thin cortex brainstem and cerebellar hypoplasia
                3. MLIS with thick cortex (Norman-Roberts syndrome)
                4. MLIS with intermediate cortex, AP gradient
                5. MLIS with thick cortex, severe brainstem and cerebellar hypoplasia (Barth microlissencephaly syndrome)
                6. Neu-Laxova syndrome
                7. Osteodysplastic primordial dysplasia (type I or type III)
            c. Extreme microcephaly with other cortical dysplasias
                1. Microcephaly with diffuse polymicrogyria (MDP)
                2. Microcephaly with asymmetric polymicrogyria (MAP)
                3. Microcephaly with agenesis of the corpus callosum and apparent fetal brain disruption (MACC)
          2. Increased without dysplasia (none known = nk)
          3. Increased with abnormal neuronal and glial proliferation (nk)
    B. Focal or multifocal
        1. Decreased proliferation or deficient induction
            a. Polymicrogyria (PMG), unlayered
            b. Polymicrogyria (PMG), 4-layered
                1. Bilateral diffuse PMG (spares occipital pole)
                2. Bilateral frontal PMG (BFP)
                3. Bilateral perisylvian PMG (BPP)
                4. Bilateral parieto-occipital PMG (BPOP)
                5. Bilateral mesial occipital PMG (BMOP)
            c. Schizencephaly (SCH)
                1. Closed-lip SCH
                2. Open-lip SCH
                3. SCH with contralateral PMG
                4. Septo-optic dysplasia-schizencephaly syndrome
            d. Polymicrogyria or schizencephaly with other abnormalities
                1. Bilateral diffuse PMG with molar tooth malformation
                2. Arima syndrome
                3. Joubert syndrome
                4. Diffuse PMG with cerebellar hypoplasia
                5. Galloway-Mowat syndrome
                6. Delleman syndrome
        2. Increased proliferation or aberrant induction without dysplasia
            a. Bilateral cingulate infolding
            b. Subcortical gyriform heterotopia ("true double cortex")
        3. Increased proliferation with dysplasia but not neoplasia
            a. Hemimegalencephaly (HMEG)
                1. Isolated HMEG
                2. Hypomelanosis of Ito with HMEG
                3. Klippel-Trenauney syndrome with HMEG
                4. Sebaceous nevus syndrome with HMEG
            b. Sublobar dysplasia
            c. Focal transmantle dysplasia
            d. Focal cortical dysplasia with balloon cells
        4. Increased proliferation with dysplasia and neoplastic potential
            a. Phakomatoses
                1. Tuberous sclerosis
                2. Neurocutaneous melanosis with HMEG
             b. Dysplastic neoplasias
                1. Dysembryoplastic neuroepithelial tumor (DNET)
                2. Gangliocytoma
                3. Ganglioglioma


II. Malformations due to abnormal neuronal migration

A. Generalized migration abnormalities
    1. Lissencephaly (LIS) and related malformations
        a. Classical lissencephaly and subcortical band heterotopia (SBH)
            1. Isolated lissencephaly sequence, X-linked (ILSX)
            2. Isolated lissencephaly sequence, 17-linked (ILS17)
            3. Isolated lissencephaly sequence,  other or unknown loci
            4. Miller-Dieker syndrome (MDS)
            5. Baraitser-Winter syndrome (BWS)
            6. Thin, posterior SBH
            7. Other patterns (PCH-SBH, SBH-PCH asymmetric PCH)
        b. Lissencephaly with absent corpus callosum, cerebellar hypoplasia. or both
            1.Lissencephaly with cerebellar hypoplasia (LCH) group congenital microcephaly, LIS grade 1)
            2. LCH with PA gradient
            3. LCH with brainstem dysplasia and neonatal death
            4. Lissencephaly with agenesis of the corpus callosum and cerebellar hypoplasia
            5. Lissencephaly with absent corpus callosum (LACC)
        c. Lissencephaly with intermediate or immature cortex
            1. Winter-Isukahara syndrome (WTS)
            2. X-linked lissencephaly with ambiguous genitalia (XLAG)
        d. Cobblestone lissencephaly
            1. Cobblestone lissencephaly only (CLO)
            2. Fukuyama congenital muscular dystrophy (FCMD)
            3. Muscle-eye~brain disease (MEB)
            4. Walker-Warburg syndrome (WWS);
    2. Other diffuse heterotopia
        a. Bilateral periventricular laminar heterotopia (BPLH)
        b. Bilateral periventricular nodular heterotopia (BPNH)
            1. X-linked BPNH
            2. X-linked BPNH with syndactyly
            3. BPNH with frontonasal malformation
    B. Focal or multifocal
        1. Subcortical heterotopia
        2. Subependymal heterotopia
        3. Combined subcontical and subependymal heterotopia
        4. Excessive single ectopic neurons in white matter

Ill. Malformations due to abnormal cortical organization
    A Generalized (nk)
    B Focal or multifocal
        1. Focal cortical dysplasia without balloon cells
        2. Microdysgenesis
        3. Other subtle cortical dysplasias

This list of malformations supplied at  the Lissencephaly Network Conference 1999, Dallas, TX.