Brief Summary
It is a rare disorder that affects pre-birth brain growth. The absence of natural convolutions (folds) in the cerebral cortex and an abnormally small head define this condition (microcephaly). In individuals with this condition, this underdevelopment of the brain causes significant intellectual disability, slow development, and repeated seizures (epilepsy). As a feature, more than 25 syndromes have lissencephaly.
Frequency
The overall incidence of lissencephaly is rare and affects approximately 1 in 100,000 newborns.
Inheritance
An autosomal dominant pattern is frequent in heterozygous mutations in the gene. When mutations in the DCX gene cause Isolated Lissencephaly, it is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome.
History of Disease
This disorder was first reported in 1904 and was considered rare until CT and MRI scans came into widespread use.
ISOLATED LISSENCEPHALY
Pathogenesis
In isolated lissencephaly, multiple gene mutations were implicated. LIS1 or PAFAH1B1 are among the best-studied cases. Lissencephaly type 1 is responsible for mutations in this gene. On chromosome 17p13.3, the LIS1 gene is localized. The gene encodes the platelet-activating factor acetyl hydrolase isoform 1B that interacts with proteins like dynein and dynactin associated with microtubules. During fetal brain formation, this association is important for proper neuronal migration. Disruption of this interaction results in Lissencephaly.
Mode of Inheritance:
ILS is inherited in an autosomal dominant pattern , which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Symptoms
1
Unusual facial appearance
2
Muscle spasms
3
Hands, Fingers or toes maybe deformed
4
Difficulty swallowing
5
Seizures
6
Severe psychomotor retardation
Signs and symptoms may vary from the patients affected. Others experience few symptoms while others might experience severe symptoms.
Social Concerns
Parents wanting to prolong the life of their child having this disorder may experience psychological and emotional challenges such as being stressed by caring tasks and having worries about the present and future life of their children especially since this commitment is a life full of hospital visits and medication.
Treatment
Thorough clinical assessment, brain imaging tests, including computerized tomography (CT) scanning and/or magnetic resonance imaging (MRI) and genetic testing such as chromosomal analysis and/or precise gene mutational analysis, are used to diagnose patients with Isolated Lissencephaly.
Unfortunately, there is no cure for this disease, but supportive care helps in some cases. Seizures may often happen but anticonvulsant medications may help. If feeding the patient becomes difficult, a gastrostomy tube is considered to help with this problem.
Clinical Trials
Title:
Combining Exome and Transcriptome Data to Unravel the Genetic Basis of the Lissencephalies
Intervention:
Diagnostic Test: Venipuncture and skin biopsy for RNA extraction
Phase:
Not applicable
Procedure:
This study will combine WES and quantitative RNA sequencing in a subgroup of the MCD spectrum. It is estimated that 80% percent of the lissencephalies can be genetically diagnosed by standard WES or WGS, leaving +/- 20% of cases unsolved. WGS will be applied in specific cases where WES remains negative (e.g., alterations in RNA expression pattern). This approach has never been applied to MCD before. Most accurate numbers can be derived from the few case series that have been published, where quantitative RNA sequencing was found to extend the diagnostic yield between 7 and 35%. These results are based on small case series, consisting of heterogenous phenotypes and are difficult to extrapolate to the proposed research set-up based on a well-delineated phenotype.
Goals:
Additional diagnostic yield of RNA seq in clinical practice
Further details at:
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05185414
https://clinicaltrials.gov/ct2/show/NCT05185414?cond=lissencephaly&draw=2&rank=1
Expert Directory
References
[4]Lissencephaly 1 (n.d.) OMIM entry #607432 (2023, May 20). Retrieved from https://omim.org./entry/607432?search=ISOLATED%20LISSENCEPHALY&highlight=isolated%20lissencephaly#inheritance
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