Lissencephaly (smooth brain) is a severe malformation of the cerebral cortex characterized by absent or decreased convolutions. that results from arrest of neuronal migration at about 10 to 14 weeks gestation. This group of malformations includes classic lissencephaly, lissencephaly with cerebellar hypoplasia, microlissencephaly, and cobblestone lissencephaly. The first three subtypes of lissencephaly are characterized by a four-layered cortex, whereas cobblestone lissencephaly is characterized by an almost complete absence of cortical layer formation, white matter abnormalities, and enlarged ventricles, brainstem, and cerebellar, especially vermis hypoplasia.
Classic lissencephaly is quite rare and manifests with severe developmental delay, spastic quadriparesis, and severe epilepsy. The lissencephaly malformation spectrum merges with subcortical band heterotopia. The thickness of the heterotopic band and the degree of pachygyria correlate well with phenotype severity. Several different patterns of lissencephaly have been recognized, and a detailed grading system has been developed based on the severity of the gyral pattern and grading along the anterior to posterior axis.
Koul et al. (2006) analyzed data from the pediatric neurology department at Sultan Qaboos University Hospital for children undergoing evaluation for developmental delay and epilepsy. Corpus callosum agenesis and lissencephaly or pachygyria formed the major group. There were 12 children (8 boys, 4 girls) with lissencephaly and their ages ranged between 15 days and 6 years (Mean age: 1 year 11 months). Seven of 12 (58.33%) children had epilepsy. The clinicoradiologic features suggested Walker-Warburg features in two children and Miller-Dieker features in three children. The epilepsy type was tonic-clonic in five, infantile spasms in one, myoclonic in one, and Lennox-Gastaut syndrome in one. The family history of developmental delay, similar to the index case, was present in two children with lissencephaly. However, the brain imaging did not reveal the abnormality.
Ehlayel et al. (2009) reported a case with new association of lissencephaly, primary immunodeficiency, and a connective tissue disorder. This association occurred in a 33-month-old boy who presented at the Allergy-Immunology Clinic of Hamad Medical Corporation in Qatar for recurrent infections.
In 1989, Banna and Malabarey analyzed the findings in four patients with lissencephaly. The main computed tomographic and magnetic resonance features were: smooth brain surface, shallow sylvian fissures resulting in a figure-eight appearance of the axial brain sections, decreased white matter and a thick brain cortex, absent or severely attenuated grey-white matter interdigitations, and dilatation of the lateral ventricles. Other associated anomalies included microcephaly, absent corpus callosum, neuronal heterotopia, and cerebellar hypoplasia.
Alorainy (2006) reviewed and analyzed the MRI studies on 808 pediatric patients (aged 3 days to 15 years) over a 3-year period. A total of 114 congenital cerebral malformations were identified in 86 of these patients via MRI. Nineteen patients were identified with lissencephaly or pachygyria complex.
Sztriha et al. (1998a) reported three neonates, one boy and two girls, born to an inbred Arab family from the United Arab Emirates with cortical dysplasia, probably agyriapachygyria, and agenesis of the corpus callosum. All three neonates in this inbred family demonstrated striking similarities that distinguished them from patients with lissencephaly and chromosome 17p deletion. All had asphyxia, intractable seizures, and increased muscle tone at birth and died in the neonatal period. Congenital microcephaly or dysmorphic features were absent. Cytogenetic abnormality, metabolic disorder, and intrauterine infection were excluded. These cases suggest a new cerebral dysgenesis syndrome with cortical dysplasia, most probably agyria-pachygyria and agenesis of the corpus callosum. Based on the occurrence in siblings of both sexes and parental consanguinity, Sztriha et al. (1998a) suggested that this syndrome may have an autosomal recessive inheritance. They further noted that mapping the gene for this syndrome may facilitate understanding of the genetic basis of this malformation and provide further insight into the mechanisms involved in cerebral development.
Sztriha et al. (1998b) reported an inbred Arab family with three neonates affected by microlissencephaly syndrome. The index patient was a male infant born by Cesarean section because of fetal distress. The parents were consanguineous of United Arab Emirates origin. Pregnancy was complicated by gestational diabetes requiring insulin treatment. On examination, he had gasping respiration. He died 10 hours after birth. Brain magnetic resonance imaging in the index case revealed very thin brain mantle with agyria-pachygyria, agenesis of the corpus callosum, and hypoplasia of the brainstem and cerebellum. Two male siblings also died soon after birth. All three neonates had microcephaly, arthrogryposis multiplex congenita, and micropenis. Sztriha et al. (1998b) suggested that microlissencepahly is a distinct entity that should be differentiated from the various other types of lissencephaly.
In 2005, Sztriha et al. described a 1-year-old boy with extreme microcephaly and a complex brain malformation. He was born at term after an uneventful pregnancy, labor, and delivery to unrelated parents of United Arab Emirates origin. On examination at the age of 12 months, he had a sloping forehead and convergent squint. Cranial magnetic resonance imaging (MRI) revealed an abnormal gyral pattern with features of the agyria-pachygyria spectrum, partial agenesis of the corpus callosum, severely hypoplastic posterior cerebellar vermis, and an abnormal foliation pattern of the cerebellar hemispheres associated with a flat and wide isthmus and pons. Although this phenotype shares some features with malformations classified as microcephaly with a simplified gyral pattern, microlissencephaly, or lissencephaly with cerebellar hypoplasia, none of the several subgroups of these categories are identical to the cerebral dysgenesis found in this patient. Sztriha et al. (2005) suggested that several processes of brain development are likely to be affected in their patient.