Lissencephaly I

Alternative Names

  • LIS1
  • Lissencephaly Sequence, Isolated
  • ILS
  • Lissencephaly, Classic
  • Subcortical Laminar Heterotopia
  • SCLH
  • Subcortical Band Heterotopia
  • SBH
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

OMIM Number

607432

Mode of Inheritance

Autosomal Dominant

Gene Map Locus

17p13.3

Description

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.

Molecular Genetics

Over 25 syndromes with lissencephaly or other neuronal migration disorders have been described. Among them are syndromes with several different patterns of inheritance including chromosomal or new mutation autosomal dominant, autosomal recessive, X-linked and unknown. Autosomal recessive inheritance seems to be very rare. The genes responsible for several of the lissencephaly syndromes have been mapped. X-linked lissencephaly has tentatively been mapped to chromosome Xq22, both Miller-Dieker syndrome and isolated lissencephaly sequence were mapped to chromosome 17p13.3, and Fukuyama congenital muscular dystrophy was mapped to chromosome 9q31-33.

Epidemiology in the Arab World

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Other Reports

Oman

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. 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. 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.

Qatar

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.

Saudi Arabia

Alorainy (2006) reviewed and analyzed the MRI studies on 808 pediatric patients (aged 3 days to 15 years) over a 3-year period.  Of the total of 114 congenital cerebral malformations identified, lissencephaly or pachygyria complex was identified in 19 patients.

United Arab Emirates

Sztriha et al. (1998a) reported three neonates, one boy and two girls, born to an inbred Emirati family with cortical dysplasia, probably agyriapachygyria, and agenesis of the corpus callosum. All three neonates had asphyxia, intractable seizures, and increased muscle tone at birth and died in the neonatal period. Cytogenetic abnormality, metabolic disorder, and intrauterine infection were excluded. Based on the occurrence in siblings of both sexes and parental consanguinity, Sztriha et al. (1998a) suggested that this new cerebral dysgenesis syndrome may have an autosomal recessive inheritance.

Sztriha et al. (1998b) reported another inbred Emirati 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. Although his 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 were 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.

 

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