Lissencephaly
Encyclopedia
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
). 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.
, failure to thrive
, seizure
s, and muscle spasticity
or hypotonia
. Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, finger
s, or toe
s.
, computed tomography
(CT), or magnetic resonance imaging
(MRI). However, these results should be interpreted cautiously since even experienced radiologists can 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 should be complemented by other methods, such as genetic studies and NMR, and the examination is not recommended as part of routine ultrasound examinations, unless family medical history or other reasons for suspecting brain malformation are present. The earliest point during gestation when it is possible to observe abnormal development of the brain surface is approximately in week 20, although ultrasound examinations in week 25-30 is more common. Up to this time, the fetal brain normally has a smooth appearance. If lissencephaly is suspected, chorionic villus sampling
can test for some lissencephaly variants, but only those with a known genetic mutation.
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), 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
.
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), 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):
tube may be considered.
Gestation
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....
, resulting in a lack of development of brain folds (gyri
Gyrus
A gyrus is a ridge on the cerebral cortex. It is generally surrounded by one or more sulci .-Notable gyri:* Superior frontal gyrus, lat. gyrus frontalis superior* Middle frontal gyrus, lat. gyrus frontalis medius...
) and grooves (sulci
Sulcus (neuroanatomy)
In neuroanatomy, a sulcus is a depression or fissure in the surface of the brain.It surrounds the gyri, creating the characteristic appearance of the brain in humans and other large mammals....
). It is a form of cephalic disorder
Cephalic disorder
Cephalic disorders are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system...
. Terms such as 'agyria' (no gyri) or 'pachygyria
Pachygyria
Pachygyria is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, the onset and severity depending on the severity of the cortical malformation...
' (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 retardationPsychomotor retardation
Psychomotor retardation involves a slowing-down of thought and a reduction of physical movements in an individual. Psychomotor retardation can cause a visible slowing of physical and emotional reactions, including speech and affect...
, failure to thrive
Failure to thrive
Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, and muscle spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
or hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
. Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, finger
Finger
A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates....
s, or toe
Toe
Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being digitigrade. Humans, and other animals that walk on the soles of their feet, are described as being plantigrade; unguligrade animals are those that walk on hooves at the tips of...
s.
Diagnosis
The diagnosis of lissencephaly is usually made at birth or soon after by ultrasoundUltrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
, computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT), or magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI). However, these results should be interpreted cautiously since even experienced radiologists can misdiagnose polymicrogyria
Polymicrogyria
Polymicrogyria is a developmental malformation of the human brain characterized by an excessive number of small convolutions on the surface of the brain...
, 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 should be complemented by other methods, such as genetic studies and NMR, and the examination is not recommended as part of routine ultrasound examinations, unless family medical history or other reasons for suspecting brain malformation are present. The earliest point during gestation when it is possible to observe abnormal development of the brain surface is approximately in week 20, although ultrasound examinations in week 25-30 is more common. Up to this time, the fetal brain normally has a smooth appearance. If lissencephaly is suspected, chorionic villus sampling
Chorionic villus sampling
Chorionic villus sampling , sometimes misspelled "chorionic villous sampling", is a form of prenatal diagnosis to determine chromosomal or genetic disorders in the fetus. It entails sampling of the chorionic villus and testing it...
can test for some lissencephaly variants, but only those with a known genetic mutation.
Causes
Causes of lissencephaly can include viralVirus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
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
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
gene (on chromosome 7), as well as other genes on the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
and on chromosome 17. Genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
is usually offered if there is a risk of lissencephaly, coupled with genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
.
Classification
The spectrum of lissencephaly is only now becoming more defined as neuroimaging and geneticsGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
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), 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 – |
PAFAH1B1 Platelet-activating factor acetylhydrolase IB subunit alpha is an enzyme that in humans is encoded by the PAFAH1B1 gene.According to one study, PAFAH1B1 interacts with VLDLR receptor activated by reelin.-Genomics:... gene mutation, which subdivides into:
Doublecortin Doublecortex; lissencephaly, X-linked , also known as DCX, is a gene.Doublecortin is a microtubule-associated protein expressed by neuronal precursor cells and immature neurons in embryonic and adult cortical structures... (DCX) gene mutation >- | Cobblestone (or Type 2) lissencephaly |
>- | Other types |
|
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 gastrostomyGastrostomy
Gastrostomy refers to a surgical opening into the stomach. Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression....
tube may be considered.
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.External links
- Lissencephaly.org.uk
- Lissencephaly Launch Pad (support)
- Lissencephaly, generic term (pdf document) - concise and thorough classification of lissencephaly by prof. Alan Verloes.
- GeneReviews/NCBI/NIH/UW entry on DCX-Related Disorders
- OMIM entries on DCX-Related Disorders
- GeneReview/NIH/UW entry on LIS1 Lissencephaly
- MRI Imaging Lissencephaly/Agyria