Authors: Cara Piccoli, MD; Sonika Agarwal, MBBS, MD, Children’s Hospital of Philadelphia Reviewed: August 2021 Lissencephaly is a rare birth defect involving an abnormally smooth brain. Children with lissencephaly can develop: There is no cure. However, there are many options that can help prevent complications from this disorder and improve quality of life. Lissencephaly means “smooth brain.” In lissencephaly there are few or no folds in the brain. During normal brain development in pregnancy, the brain starts as a smooth surface. Over time, it develops folds known as gyri. Normally, brain cells (neurons) first form deep in the brain. Then they move outward, as layers and folds of brain develop. This takes place prior to birth. The peak time for this to happen is during second trimester, or 3 to 5 months into pregnancy. In lissencephaly, the neurons do not reach their final destination. They do not form normal bumps and grooves in the brain. There are two major types of lissencephaly Pachygyria is the name for a mild form of the condition. Lissencephaly can be diagnosed on prenatal ultrasound. Another important tool for early detection is fetal MRI (magnetic resonance imaging). Fetal MRI can confirm findings and provide more detail even prior to birth. It can check the severity of the condition and look for any other brain malformations. The condition can be diagnosed in infancy and childhood using: Symptoms of lissencephaly are usually seen in infancy. Common symptoms include: Lissencephaly typically results in moderate or severe symptoms. The symptoms can put babies at risk for potentially life-threatening complications. These complications can include: Lissencephaly is usually caused by a genetic mutation or also due to non-genetic causes. A genetic mutation is a change in a person’s DNA. Genetic mutations can be inherited from parents, or they can occur randomly. New, random changes in DNA are called de novo mutations. Several genes have been identified to be associated with lissencephaly. Some common genes implicated in lissencephaly are: LIS1, RELN, DCX and ARX, TUBA1A, NDE1, KATNB1, and CDK5. In rare cases, lissencephaly can be caused by: Frequently, a cause cannot be found. Several lab tests and types of imaging can be helpful in determining the type of lissencephaly and its cause. MRI and CT scans can be helpful in diagnosing this condition. Ultrasounds can also be used for infants. MRI provides the best quality image. It can be used in pregnancy, too, for a diagnosis prior to birth. Genetic testing may be helpful in determining if there is a genetic cause for the condition. Genetic studies may be helpful for family planning. They can also help doctors determine the risk of complications. There are several genetic tests available. Often, more than one test is recommended. Some patients may need multiple tests to diagnose or rule out a genetic cause. Blood and saliva are the most common samples used for genetic testing. The tests often takes several weeks or months to produce results. Examples of recommended genetic tests include: Various blood and urine testing may be recommended. This testing can: There is no cure for lissencephaly. Most children do require treatment for complications. Treatments depend upon disease severity and additional conditions. Some children benefit from medication to help treat: Surgery is frequently recommended for patients with lissencephaly. Surgery is typically used for: These therapies can help with: These therapies can help with: Specialized equipment can help children: Many children benefit from a tube that allows caregivers to give them nutrition and medications. Special diets may be prescribed to maximize nutrition. Diets can also help treating seizures. Tools and technologies are available to help children with this disorder better express their needs. There is no cure for lissencephaly. Symptoms are typically moderate or severe. However, severity differs depending upon the amount of the brain involved. Early and consistent therapy can be very helpful for some children. Therapies may include physical, occupational, speech, or vision therapy. Most children with lissencephaly need daily medications to: Some children benefit from a feeding tube for extra nutrition. This disorder is often found alongside hydrocephalus, a buildup of fluid around the brain. In these cases, shunt may be needed to relieve pressure in the head. Lissencephaly can occur with other brain abnormalities, including: Lissencephaly Foundation JCN: NICU Series — Cortical malformations: Polymicrogyria, pachygyria, lissencephaly, heterotopia Child Neurology Foundation (CNF) solicits resources from the community to be included on this webpage through an application process. CNF reserves the right to remove entities at any time if information is deemed inappropriate or inconsistent with the mission, vision, and values of CNF. ClinicalTrials.gov for Lissencephaly (birth to 17 years) These are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently. ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details. Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits. The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only. CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. Fukuyama type congenital muscular dystrophy [Internet]. NORD (National Organization for Rare Disorders). 2018 [cited 2021Aug1]. Available from: https://rarediseases.org/rare-diseases/fukuyama-type-congenital-muscular-dystrophy Hsieh DT, Jennesson MM, Thiele EA, Caruso PA, Masiakos PT, Duhaime A-C. Brain and Spinal manifestations of Miller-Dieker syndrome. Neurology: Clinical Practice. 2013;3(1):82–3. PMID: 23634385; https://doi.org/10.1212/CPJ.0b013e318278be63 Isolated lissencephaly sequence: MedlinePlus Genetics [Internet]. MedlinePlus. U.S. National Library of Medicine; 2020 [cited 2021Aug1]. Available from: https://medlineplus.gov/genetics/condition/isolated-lissencephaly-sequence Lissencephaly information page [Internet]. National Institute of Neurological Disorders and Stroke. U.S. Department of Health and Human Services; 2019 [cited 2021Aug4]. Available from: https://www.ninds.nih.gov/Disorders/All-Disorders/Lissencephaly-Information-Page Lissencephaly with cerebellar hypoplasia: MedlinePlus Genetics [Internet]. MedlinePlus. U.S. National Library of Medicine; 2020 [cited 2021Aug1]. Available from: https://medlineplus.gov/genetics/condition/lissencephaly-with-cerebellar-hypoplasia Lissencephaly [Internet]. Genetic and Rare Diseases Information Center. U.S. Department of Health and Human Services; 2007 [cited 2021Aug1]. Available from: https://rarediseases.info.nih.gov/diseases/12291/lissencephaly Lissencephaly [Internet]. NORD (National Organization for Rare Disorders). 2018 [cited 2021Aug1]. Available from: https://rarediseases.org/rare-diseases/lissencephaly Miller-Dieker syndrome: MedlinePlus Genetics [Internet]. MedlinePlus. U.S. National Library of Medicine; 2020 [cited 2021Aug1]. Available from: https://medlineplus.gov/genetics/condition/miller-dieker-syndrome Muscle eye brain disease [Internet]. Genetic and Rare Diseases Information Center. U.S. Department of Health and Human Services; 2016 [cited 2021Aug4]. Available from: https://rarediseases.info.nih.gov/diseases/156/muscle-eye-brain-disease Walker Warburg syndrome [Internet]. NORD (National Organization for Rare Disorders). 2021 [cited 2021Aug1]. Available from: https://rarediseases.org/rare-diseases/walker-warburg-syndrome SUMMARY
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Disorder Overview
DESCRIPTION
SIGNS AND SYMPTOMS
CAUSES
DIAGNOSIS AND LABORATORY INVESTIGATIONS
Brain Imaging
Genetic Testing
Other Testing
TREATMENT AND THERAPIES
Medication
Surgery
Physical and occupational therapy
Speech and swallowing therapy
Wheelchairs, walkers and other mobility equipment
Feeding equipment and specialized diets
Communication aids and tools
OUTLOOK
RELATED DISORDERS
Resources
Organizations
The Lissencephaly Foundation empowers families and educates communities by promoting a day of awareness, hosting family gatherings, providing family support, medical equipment, and educational materials. The Lissencephaly Foundation Inc Facebook page is where you will find the current awareness events, family support, programs, and more. The Foundation hosts a private Facebook group, Lissencephaly Network, with over 2,700 members worldwide.Publications
Podcast from SAGE Neuroscience and Neurology/Journal of Child Neurology (JCN). Dr. Sonika Agarwal of Children’s Hospital of Philadelphia talks about Cortical malformations: Polymicrogyria, pachygyria, lissencephaly, heterotopia.Research
References
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