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LISSENCEPHALY

Lissencephaly, which literally means smooth brain, is a rare brain formation disorder caused by defective neuronal migration during the 12th to 24th weeks of gestation, resulting in a lack of development of brain folds (gyri) and grooves (sulci).[1] It is a form of cephalic disorder. Terms such as ‘agyria’ (no gyri) or ‘pachygyria’ (broad gyri) are used to describe the appearance of the surface of the brain. Children with lissencephaly are severely neurologically impaired and often die within several months of birth.

 

Symptoms
Affected children display severe psychomotor retardation, failure to thrive, seizures, and muscle spasticity or hypotonia.[4] Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, fingers, or toes.

[edit] Diagnosis
The diagnosis of lissencephaly is usually made at birth or soon after by ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). However, these results should be interpreted cautiously since even experienced radiologists can be misdiagnose polymicrogyria, a different developmental malformation of the brain, as lissencephaly.

Before birth, complex ultrasounds performed routinely during pregnancy may indicate the presence of cerebral abnormality, but this method of diagnosis is not reliable, and an absence of abnormal cerebral pathology should only inspire cautious optimism at best. In any case, diagnosis by ultrasound probably cannot be reliably made until 26 to 28 weeks, when the normal gyri and sulci become well defined. Up to this time, the fetal brain normally has a smooth appearance.[5] If lissencephaly is suspected, chorionic villus sampling can test for some lissencephaly variants, but only those with a known genetic mutation.

[edit] Causes
Causes of lissencephaly can include viral infections of the uterus or the fetus during the first trimester, or insufficient blood supply to the fetal brain early in pregnancy. There are also a number of genetic causes of lissencephaly, including mutation of the reelin gene (on chromosome 7),[6] as well as other genes on the X chromosome and on chromosome 17. Genetic counseling is usually offered if there is a risk of lissencephaly, coupled with genetic testing.

[edit] Classification
The spectrum of lissencephaly is only now becoming more defined as neuroimaging and genetics has provided more insights into migration disorders. There are around 20 different types of lissencephaly which make up the spectrum. Other causes which have not yet been identified are likely as well.

Different systems for classifying lissencephaly exist. One major distinction is “classic” (type I) vs. “cobblestone” (type II),[7] but some systems add additional forms that fit into neither of these categories.

Some types of lissencephaly are described below (OMIM numbers are included where available):

Category Types
Classic (or Type 1) lissencephaly – 607432 LIS1: lissencephaly due to PAFAH1B1 gene mutation, which subdivides into:
type 1 isolated lissencephaly (601545)
Miller-Dieker syndrome (247200)
LISX1: lissencephaly due to doublecortin (DCX) gene mutation (300121)
lissencephaly, type 1, isolated, without other known genetic defects

Cobblestone (or Type 2) lissencephaly Walker-Warburg syndrome (236670), also called HARD(E) syndrome
Fukuyama syndrome (253800)
Muscle-eye-brain disease (MEB) (253280)

Other types LIS2: Norman-Roberts syndrome (mutation of reelin gene, 257320)
LIS3: TUBA1A, 611603
LISX2: ARX, 300215
Microlissencephaly (lissencephaly and microcephaly)[8] [edit] Treatment
Treatment for those with lissencephaly is symptomatic and depends on the severity and locations of the brain malformations. Supportive care may be needed to help with comfort and nursing needs. Seizures may be controlled with medication and hydrocephalus may require shunting. If feeding becomes difficult, a gastrostomy tube may be considered.

[edit] Prognosis
The prognosis for children with lissencephaly varies depending on the degree of brain malformation. Many individuals show no significant development beyond a 3- to 5-month-old level. Some may have near-normal development and intelligence. With modern medications and care, some children live into their teens. Respiratory problems are the most common causes of death.

[edit] External links
lissencephaly at NINDS
Lissencephaly.org.uk
Lissencephaly Launch Pad (support)
Lissencephaly, generic term (pdf document) – concise and thorough classification of lissencephaly by prof. Alan Verloes.
GeneReview/NIH/UW entry on DCx Lissencephaly
GeneReview/NIH/UW entry on LIS1 Lissencephaly
[edit] References
1.^ Dobyns, WB. Developmental aspects of lissencephaly and the lissencephaly syndromes. Birth Defects Orig Artic Ser 1987; 23:225.
2.^ Bauman, ML. Neuroembryology–clinical aspects. Semin Perinatol 1987; 11:74.
3.^ Jones, KL. Smith’s Recognizable Patterns of Human Malformation, 6th ed. Elsevier Saunders, Philadelphia 2006.
4.^ Jones, KL. Smith’s Recognizable Patterns of Human Malformation, 6th ed. Elsevier Saunders, Philadelphia 2006.
5.^ Dorovini-Zis K; Dolman CL. Gestational development of brain. Archives of Pathologic Laboratory Medicine 1977 Apr;101(4):192-5.
6.^ Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA. (2000) Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet. 26(1):93-6. PMID 10973257

7.^ Forman MS, Squier W, Dobyns WB, Golden JA (October 2005). “Genotypically defined lissencephalies show distinct pathologies”. J. Neuropathol. Exp. Neurol. 64 (10): 847–57. doi:10.1097/01.jnen.0000182978.56612.41. PMID 16215456. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0022-3069&volume=64&issue=10&spage=847.
8.^ Microlissencephaly
[hide]v • d • eCongenital malformations and deformations of nervous system (Q00-Q07, 740-742)

Brain Neural tube defect Anencephaly (Acephaly, Acrania, Iniencephaly) · Encephalocele · Arnold-Chiari malformation

Other Microcephaly · Congenital hydrocephalus (Dandy-Walker syndrome)

other reduction deformities (Holoprosencephaly, Lissencephaly, Pachygyria, Hydranencephaly)

Septo-optic dysplasia · Megalencephaly

CNS cyst (Porencephaly, Schizencephaly)

Polymicrogyria (Bilateral frontoparietal polymicrogyria)

Spinal cord Neural tube defect Spina bifida · Rachischisis

Other Currarino syndrome · Diastomatomyelia · Syringomyelia

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