The term Lisencephaly Means"smooth brain"and is used to refer to a neurological disorder in which there is a Insufficiency of the development of the grooves and cerebral convolutions (Mota et al., 2005).
This type of pathology is a congenital malformation caused by a neuronal migration disorder (Hernández et al., 2007), that is, in the Process that the nerve cells follow from the place of origin towards its final location in the cerebral cortex during the embryonic period (Cleveland Clinic, 2016).
The clinical course of lysencephaly may include generalized growth retardation, muscle spasms, seizures, severe psychomotor retardation, Facial anomalies, among others (Cleveland Clinic, 2016).
In addition, this type of neuronal migration disorder is often associated with other medical conditions such as Miller-Dieker syndrome and Walker-Warburg syndrome (Cleveland Clinic, 2016).
There is currently no curative treatment for lisencephaly. The prognosis for those affected by this pathology varies considerably between The different cases, depending on the degree of cerebral malformation: some will not survive at 10 years of age, while others may show a Severe developmental delay and growth, and others a near normal physical and cognitive development (National Institute of Neurological Disorders and Stroke, 2015).
Characteristics of lysencephaly
Lysencephaly is a genetic brain malformation characterized by the absence of normal convolutions in the cerebral cortex (Cortical Foundation, 2012).
The Cerebral convolutions Or twists are each of the folds on the outer surface of the brain, separated from each other By a series of grooves called fissures or cerebral fissures. (Wordreference, 2005).
Specifically, lysencephaly can manifest itself with different degrees of affection, characterized by the use (agiria) or Reduction (paquiria) of the cerebral convolutions (Palacios Marqués et al., 2011).
The agiria, refers to the absence of folds in the brain surface and is usually used as a synonym of"complete lysencephaly", while the pachyria or presence of few thicker folds, is used as a synonym of "Incomplete lisecenphaly"(Mota et al., 2005).
Thus, lysencephaly results from a disorder of brain development (Palacios Marqués et al., 2011) resulting from a group of abnormalities in neuronal migration (Mota et al., 2005).
When the nervous system is forming and developing during the prenatal stage, neurons must travel from the primitive layers or areas to the cerebral cortex (Hernández et al., 2007),
During embryonic growth, newly formed cells that are later to become specialized nerve cells, must miter From the surface of the brain to a pre-programmed final location. This migration takes place in successive moments from the seventh week of gestation to The twentieth (National Organization for Rare Disorders, 2015):
There are several mechanisms by which the neurons reach their final location: some reach their location through the displacement along of the Glial cells While others do so through mechanisms of chemical attraction.
The ultimate purpose of this displacement is to form a 6 layer laminar structure in the cerebral cortex, essential for the correct functioning and Development of Cognitive functions (Hernández et al., 2007).
When an interruption of this process takes place and a lisecenfalia develops, the cerebral cortex presents an abnormally thick structure of 4 Poorly organized layers (Hernández et al., 2007).
Therefore, at the anatomical level, lysencephaly can be defined by the presence of agiria or paquiria and even the formation of a double crust (Heterotopy) (Mota et al., 2005).
About us
Lysencephaly is a group of rare brain malformations (Hernández et al., 2007).
Although there are no statistical data on the prevalence of milder forms of lysencephaly, the classical form has a frequency of 11.7 per million newborns (Hernández et al., 2007).
The absence of recent data is mainly due to the sporadic occurrence of this pathology, and to the fact that a large number of cases Were left undiagnosed due to the absence of technical doctors (National Organization for Rare Disorders, 2015).
However, the use of advanced neuroimaging techniques in neurological evaluations has now allowed an accurate recognition of this Pathology and thus an increase in diagnosed cases (National Organization for Rare Disorders, 2015).
Characteristic signs and symptoms
Lysencephaly is a neurological disorder that is characterized by producing a smooth or completely partial brain surface and therefore, a (Lo Nigro et al., 1997; Jhons Hopkins University, 2016).
The classic forms are associated with the presence of an abnormally thick cerebral cortex composed of 4 primitive layers, a mixture of agiria and Pituitary, neuronal heterotopia, dilated and dysmorphic cerebral ventricles and, in many cases, with hypoplasia of the hard body (Lo Nigro et al., 1997; Johns Hopkins University, 2016).
In addition to these characteristic anatomical findings, affected individuals may also have other associated brain malformations, such as Such as microcephaly (National Organization for Rare Disorders, 2015).
All structural alterations will produce a wide range of medical signs and symptoms (National Organization for Rare Disorders, 2015):
- Convulsions.
- Intellectual deficit.
- Generalized delay of growth.
- Deficit in motor skills.
- Craniofacial malformations.
- Muscle tone decreased (hypotonia) or increased (hypertonia).
Types of lysencephaly
There is a wide variety of classifications of lysencephaly based on pathological, genetic and anatomical findings (Hernández et al., 2007).
Despite this, one of the most common classifications is that referring to type I and type II of lysencephaly:
- Lisencephaly type I or Bielschowsky type and S a sporadic type in which the cortex has some organization, although it is found Formed by fewer layers than usual, generally 4 layers (Palomero-Domíngez et al., 1998).
- Lisencephaly type II S Is characterized by an unstructured cerebral cortex in which no layer can be recognized (Polychromatic) that develops with serious muscular alterations, neurological dysfunction, Hydrocephalus Y Encephalocele (Palomero-Domíngez et al., 1998).
In addition to this, there are other classifications based on the associated malformations and the etiological cause. Based on these criteria, lysencephaly Can be classified in (Orphanet Encyclopedia, 2004):
- Classical Lisencephaly (Type I) I Cases of lysencephaly due to a mutation of the LIS1 gene (isolated lysencephaly type 1 and Mieller-Deker syndrome); Lysencephaly due to a mutation of the DCX gene; Lysencephaly type 1 isolated without known genetic defects.
- X-linked Lisencephaly with agenesis of the corpus callosum .
- Lysencephaly with cerebellar hypoplasia .
- Microlisencephaly .
- Lisencephaly type II : Includes the Walker-Warburg syndromes, Fukuyama, among others.
Causes
Research that has attempted to find the specific causes of lysencephaly indicates that there may be genetic etiological factors and not Genetic: intrauterine infection; Cerebral ischemia or deficient supply of oxygen to the brain during fetal development; Alteration or absence of a Chromosome 17 region; Linked autosomal recessive transmission of the X chromosome (National Organization for Rare Disorders, 2015).
The causes of this pathology are heterogeneous, approximately 76% of the cases diagnosed have primary genetic alterations, whereas The other cases have some association with another set of environmental factors (maternal exposure to retinoic acid, ethanol, radiation or Infectious processes, 2007).
Lysencephaly is generally considered to be a fundamentally genetic pathology associated with different disorders in some of the following Genes: LIS1, 14-3-3, DCX, REELIN and ARX (Nall, 2014).
On the other hand, the scientific evidence suggests that in isolated cases of lysencephaly, this pathology may result from the presence of mutations in al Least two different genes (National Organization for Rare Disorders, 2015):
- LIS1 , Located on the short arm (p) of chromosome 17. It is a gene that regulates the production of a protein Acetylhydrolase activator of platelets) that plays an important role in the development of the outer layer of the brain.
- XLIS , Located on the long arm (q) of the X chromosome. According to specialists, this gene is responsible for the regulation of a protein (Doublecortin -DCX-) which is essential for the neural migration process to evolve effectively.
In the case of the LIS1 gene, such mutations may occur randomly sporadically or may result from chromosomal rearrangements of one of the Parents On the other hand, in the case of the XLIS gene, mutations can also occur at random in the absence of a family history and in other cases Appears as an inherited condition linked to the X chromosome (National Organization for Rare Disorders, 2015).
Medical Pathologies Associated with Lysencephaly
Lysencephaly, in addition to presenting in isolation showing the structural alterations and clinical symptoms characteristic of this pathology, May appear to be associated with other genetic diseases (Nall, 2014):
- Miller-Dieker Syndrome : This pathology results from a mutation in a gene located on chromosome 17p13. A cynical level is characterized By the presentation of classical lissencephaly, facial anomalies, severe developmental disorder, epilepsy or feeding problems (Orphanet, 2005).
- Walker-Warburg syndrome : This pathology is a congenital form of muscular dystrophy that is associated with the presence of abnormalities Brain and necklaces. At the clinical level, Walker-Warburg syndrome is characterized by the presence of type II lysecephaly, hydrocephalus, hypoplasia of the Brain stem and cerebellum, generalized muscular hypotonia, absence or poor psychomotor development, ocular involvement and convulsive episodes (Orphanet, 2011).
Diagnosis
Lysencephaly can be diagnosed before birth, approximately at the end of the second trimester, since it is from that moment when the Cerebral convolutions are visible on ultrasound scans (Palacios Marqués et al., 2011).
Ultrasound techniques routinely used in maternal gestational controls may indicate the presence of abnormalities and Brain abnormalities, however, should be complemented with other diagnostic techniques (Cortical Foundation, 2012).
When there is a suspected ultrasonography of lysencephaly, other secondary magnetic resonance Or studies Genetic factors to detect possible alterations (Palacios Marqués et al., 2011).
In addition to this diagnostic route, when there is a compatible family history or history of lysencephaly, it is possible to perform other tests as the amniocentesis (Removal of amniotic fluid surrounding the fetus) and sampling of chorionic villi (removal of a tissue sample from An area of the placenta) to identify the presence of genetic alterations (National Organization for Rare Disorders, 2015).
Despite this, it is more common that the diagnosis of lysencephaly is performed after birth through the use of Computed tomography wave Magnetic resonance imaging (Cortical Foundation, 2012).
Treatments
There is no curative intervention for lisencephaly, it is a pathology that can not be reversed (Nall, 2014).
The treatments used are aimed at improving the associated symptomatology and secondary medical complications. For example, the use of Gastrostomy to overcome feeding difficulties, surgical referral to drain a possible hydrocephalus or the use of drugs Antiepileptic drugs to control seizures (Nall, 2014).
Therefore, the usual treatment for lysencephaly is directed towards the specific symptoms that appear in each case and requires the effort Coordinated by a broad team of specialists: pediatricians, neurologists, etc. (National Organization for Rare Disorders, 2015).
Prognosis of people affected by lysencephaly
The medical prognosis of an individual suffering from lysencephaly depends fundamentally on the severity of lysencephaly (Nall, 2014).
In the most severe cases of lysencephaly, the affected person may not be able to develop physical and cognitive abilities beyond the Typical of a child between the ages of three and five months (Nall, 2014).
In general, children with severe impairment have a life experience of approximately 10 years. Being the most common causes of death, Aspiration or drowning with food or liquids, respiratory diseases or convulsions (Nall, 2014).
On the other hand, there are cases of children with mild lissencephaly who may experience a normalized development, more adjusted to their age group, gender and School level (Nall, 2014).
Bibliography
- Cleveland Clinic. (2016). Lissencephaly . Obtained from Cleveland Clinic.
- Cortical Foundation. (2012). Lissencephaly . Retrieved from the Cortical Foundation.
- Hernández, M., Bolte, L., Mesa, T., Escobar, R., Mellado, C., & Huete, I. (2007). Lisencephaly and epilepsy in pediatrics. Rev Chil Pediatr , 78 (6), 615-620.
- Johns Hopkins University. (2016). LISSENCEPHALY . Retrieved from the Online Mendelian Inheritance in Man OMIM.
- Nall, R. (2014). Lissencephaly . Retrieved from Healthline.
- NIH. (2015). Lissencephaly . Retrieved from the National Institute of Neurological Disorders and Stroke.
- NORD. (2015). Lissencephaly . Retrieved from the National Organization for Rare Disorders.
- Orphanet. (2005). Miller-Dieker Syndrome . Obtained from Orphanet.
- WebMed. (2016). Lissencephaly . Obtained from WebMed.