Autosomal recessive type I lissencephaly

Abstract

Lissencephaly (LIS) is a brain malformation manifested by a smooth cerebral surface, thickened cortical mantle and microscopic evidence of incomplete neuronal migration, excluding polymicrogyria and other cortical dysplasias. It is important to consider LIS in the diagnosis of developmental delay as many patients may be diagnosed as cerebral palsy. It may have familial occurrence and can occur in sibs of same family often leading to a diagnostic problem. Several lissencephaly syndromes have been described. Here a familial syndrome of lissencephaly is reported. Autosomal recessive inheritance is suggested by recurrence in sibs within the same family, but germ cell mosaicism for a dominant mutation cannot be excluded.

Ocular manifestations of a rare case of Miller-Dieker syndrome

“…Complete LIS is synonymous with agyria whereas incomplete LIS refers to brain with shallow sulci and a relatively smooth surface. 2 Macroscopic abnormalities of type I LIS on MR imaging include: agyria, mixed agyria/pachygyria or complete pachygyria, a thick cerebral cortex, incomplete opercularisation resulting in a shallow sylvian fissure and the typical "figure of eight" appearance of the brain, hypoplastic corpus callosum, persistent septum cavum pellucidum and dilatation of the posterior horns of the lateral ventricles [colpocephaly]. 5 Type II LIS[cobblestone] can be associated with Walker Warburg syndrome, Muscleeye-brain disease and Fukuyama congenital muscular dystrophy.…”

“…1 Classical LIS is a severe brain malformation caused by an arrest of neuronal migration at 9-13 weeks of gestation and is characterized by a smooth cerebral surface, abnormally thick and poorly organized cortex with four primitive layers, diffuse neuronal heterotopia, enlarged and dysmorphic ventricles and hypoplasia of the corpus callosum. 2 Classic LIS may be an isolated lissencephaly sequence or associated with either Miller-Dieker syndrome or Norman-Roberts syndrome. Classical LIS has been associated with few genes like LIS1, ARX, DCX and TUBA3.…”

A Forensic Autopsy Case of Lissencephaly for Evaluating the Possibility of Child Abuse

“…

Introduction

Lissencephaly ('smooth brain' ) is a severe cerebral malformation which can be classified as type I, II, or III. 1) In type I lissencephaly, neuronal migration is impeded during brain development, resulting in agyria/pachygyria of the cerebral cortex, whereas in types II and III, more severe malformations, such as polymicrogyria or hypoplastic brain stem, can occur. 1,

…”

“…3) Type I lissencephaly often occurs in genetic syndromes such as Miller-Dieker syndrome (MDS) and Norman-Roberts syndrome (NRS) and can also occur by itself in a condition called isolated lissencephaly sequence (ILS). 1) Although all lissencephaly syndromes are rare, MDS is relatively common among type I lissencephaly and is known for its cytogenetic abnormality on chromosome 17, especially the 17p13.3 deletion, which is frequently shared by ILS. 4) The cytogenetic abnormalities found in MDS and ILS are visible or submicroscopic deletions detectable through chromosome banding or chromosomal fluorescence in situ hybridization (FISH) for the LIS1 gene (also known as PAFAH1β 1) locus at 17p13.3, whereas in NRS, chromosomal analyses are frequently normal.…”

“…7,8) In patients with ILS, facial phenotypes are normal except for features associated with lissencephaly itself. 1) Patients frequently show severe hypotonia, feeding problems, frequent pneumonia, and seizure at early ages. 9) Because many deleterious phenotypes which are frequently existing in lissencephaly syndrome, including psychomotor retardation, seizures that are often intractable, severe developmental retardation, and chronic feeding problems, the lifespans of patients are usually shortened.…”