Working together toward a cure
What is MYT1L Neurodevelopmental Syndrome?
MYT1L Neurodevelopmental Syndrome is a rare genetic disorder caused by a deletion, duplication, spelling error or other change in the MYT1L gene, which provides the brain with instructions for development. Most often, it occurs spontaneously during or before conception and is not inherited from either parent. More rarely, a parent may be affected themselves by MYT1L or be mosaic for a MYT1L difference, which may cause the parent to be unaffected but to pass the MYT1L gene down to a child.
Common Features
Diagnosis
Support
and Management
​​​While every individual with MYT1L syndrome is unique, most people experience one or more of the following symptoms:
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Intellectual disability or significant learning differences
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Autism spectrum disorder or other behavioral challenges
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​Significant emotional dysregulation
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​Aggressive behavior and impulsivity
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Difficulty tolerating frustration
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Developmental delays affecting speech and motor skills
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​Attention deficit hyperactivity disorder
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Low muscle tone (hypotonia)
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Epilepsy
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Strabismus, Cortical Visual Impairment (CVI) or other vision abnormalities
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Subtle physical features, which may vary from person to person
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Increased appetite and weight, leading to obesity, which may begin any time from the first few months of life to late childhood or adolescence
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MYT1L syndrome is diagnosed through genetic testing, such as microarray analysis (which can often detect duplications and deletions) or whole exome sequencing (which may be needed to detect spelling errors and other smaller variants). This testing is often recommended when a child shows developmental differences or related symptoms. The testing methods needed to detect MYT1L syndrome have become widely available only in the last 10 to 15 years. It is likely that there are many older individuals with undiagnosed MYT1L gene differences.
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Although there is currently no cure for MYT1L syndrome, early intervention and individualized support can make a big difference. Therapies such as speech, occupational, and physical therapy can help children achieve milestones and thrive. With the right care and understanding, individuals with MYT1L syndrome can lead fulfilling lives.
The MYT1L gene is located on chromosome 2 in a specific area called 2p25.3.
The MYT1L gene is located on the short arm of chromosome 2 (commonly referred to as "2p"), in a specific region called 2p25.3.
Short arm of chromosome 2 ("2p")
Adapted from: UCSC Genome Browser
The 2p25.3 region contains several recognized genes other than MYT1L, and people with MYT1L syndrome due to a 2p25.3 deletion often have additional genes impacted. Some 2p25.3 deletions are "terminal deletions," which means that a piece is missing from the terminal end of 2p, from position 0, up to and including all or part of the MYT1L gene. Other deletions, referred to as "interstitial," occur within the 2p25.3 region, but do not include the tip of 2p. It is believed that most if not all of the neurodevelopmental symptoms in individuals with deletions limited to the 2p25.3 region result from loss of function of the MYT1L gene. Differences in the TMEM18 gene, also in the 2p25.3 region, have been found to have a strong association with obesity in both children and adults (see Publications).
2p25.3 region of the short arm of chromosome 2
Adapted from: UCSC Genome Browser
The MYT1L gene itself contains over 500,000 individual locations called "nucleotides," often referred to by the letters A, T, G and C. The specific sequence ("spelling") of these letters within the gene is important for the correct functioning of the gene. In many people with MYT1L syndrome, instead of a deletion, there is a spelling error. Spelling errors can occur because of missing letters, duplicated letters, incorrect letters, or in some cases more complex rearrangements. When this occurs, it can result in either a "nonsense" mutation or a "missense" mutation. In a nonsense mutation, the copy of the gene with the mutation is non-functional, resulting in loss of function (as occurs with deletions). In a missense mutation, the gene is sufficiently functional to produce a protein, but the protein may not function as intended.
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Because of the number of nucleotides that can result in a misspelling and the number of ways these nucleotides can be rearranged, many people with MYT1L syndrome due to a misspelling are completely unique — there is no other individual known in the world with the exact same misspelling. This can make it difficult for doctors to predict the impact of any one type of misspelling. Those misspellings identified as nonsense mutations are generally assumed to be "pathogenic" (i.e., to cause MYT1L syndrome due to loss of function), while it is much harder to predict the impact of missense mutations. This is an area of active research.
Illustration of missense compared to nonsense mutations or deletions: Every person has two copies of the MYT1L gene. If both are functional they make a certain amount of MYT1L protein (illustrated as a red lego). If a person has a deletion or nonsense mutation, they only make half as much of the protein, resulting in MYT1L syndrome. Individuals with missense mutations may make the normal amount of protein, but half of it might be misformed or misfolded because of the spelling error. Each of these atypical proteins could be pretty unique, and it can be harder to tell if they will all cause a disease. Adapted with permission from Joseph Dougherty, PhD, Washington University School of Medicine.