What are the other Names for this Condition? (Also known as/Synonyms)

• MYT1L Gene Syndrome

What is MYT1L Syndrome? (Definition/Background Information)

• MYT1L Syndrome is an uncommon genetic disorder that manifests as developmental delays, intellectual disabilities, and excess weight gain in newborn children (congenital manifestation). It develops when the normal function of the MYT1L gene, which is responsible for brain development and located on chromosome 2, is affected
• This chromosomal anomaly is known to develop from sporadic mutations; presently, a case of inheritance (from one’s parents) is not reported. MYT1L Syndrome may be diagnosed through specialized genetic testing. In some children, the condition may be mild and hence can also remain undiagnosed
• Following a diagnosis, the condition may be managed based on the presenting symptoms and extent of involvement of the body systems. The treatment may involve physician experts from several specialties, and can include speech and language therapy, use of walking aids, seizure control, behavior modification, and surgery (if needed)
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with MYT1L Syndrome are able to cope well through adequate treatment and supportive care. Some of the abnormalities may improve over time

Who gets MYT1L Syndrome? (Age and Sex Distribution)

• The incidence of MYT1L Syndrome is presently unknown but it is a very rare disorder
• In many cases, individuals with mild signs and symptoms may be undiagnosed in their lifetime. Hence, a true incidence of the disorder may be difficult to estimate
• MYT1L Syndrome is a congenital disorder, and the presentation of symptoms may occur at or following the birth of the child
• Both males and females are equally affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for MYT1L Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for MYT1L Syndrome.

• A positive family history may be an important risk factor. However, presently, no cases of the syndrome have been recorded as being inherited
• Currently, no environmental and lifestyle (including dietary) factors have been implicated
• The syndrome is not caused by what the expectant mother does or does not do, either prior to or during pregnancy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of MYT1L Syndrome? (Etiology)

MYT1L Syndrome is caused when the normal functioning of the MYT1L gene (or myelin transcription factor 1 like gene) is affected resulting in a variable set of signs and symptoms. This gene dysfunction may take place in the following manner:

• Loss of one copy of the gene due to deletion of chromosomal material on which it is located
• The copy of the gene is altered leading to a loss of function or abnormal function. A vast majority of cases occur de novo i.e., spontaneously, in the absence of any family history
• A positive family history (genetic inheritance) in MYT1L Syndrome has not been currently reported

MYT1L gene dysfunction causes neurodevelopmental abnormalities that may be mild or severe depending on the extent of dysfunction.

• The MYT1L gene is involved in regulating certain other genes (via chemical pathways) that are important for the growth and development of the brain. The gene is located on chromosome 2 on the short arm (p) at band p25.3
• There are two chromosomes numbered 2. Children with MYT1L Syndrome typically will have one (chromosome 2) in normal condition, while the other is abnormal

It is important to note that a child’s development and future is not only influenced by the chromosome material duplicated/deleted and genes involved, but also by other factors such as one’s environment, involvement of other genes, and unique personality.

Additional (general) information on chromosomes, which is helpful in understanding the disorder:

Chromosomes are microscopic thread-like protein structures present in each cell nucleus that carry genetic information in the form of DNA (deoxyribonucleic acid). DNAs are nucleic acids that encodes the genetic information of any organisms; a basic unit of the DNA is termed a gene with a specific set of instructions and a defined function. Each chromosome is “X” shaped with a center, called the centromere, and two short arms (termed p arms) and two long arms (termed q arms).

Humans have 46 chromosomes in the cell nucleus, in 23 pairs, of which one pair is named the sex chromosome. In males, it is designated XY, for chromosome X and chromosome Y; while, in females, it is designated XX, for a pair of chromosome X. The other 22 pairs of chromosomes are numbered chromosome 1 through 22, approximately according to size (with chromosome 1 being the largest; chromosome 21 being the smallest) and are referred to as autosomes or somatic chromosomes. During conception, the embryo inherits one copy of each chromosome from each parent (i.e., mother and father). Any alteration in the chromosome numbers or structure, such as via addition or deletion of chromosomal material, can result in mild to severe genetic abnormalities that may manifest as birth defects, growth delays, and intellectual disabilities.

What are the Signs and Symptoms of MYT1L Syndrome?

The signs and symptoms of MYT1L Syndrome may be significantly different from one individual to another. The degree of signs and symptoms are often related to the amount of chromosome material deleted and the genes affected and/or its dysfunction.

The commonly noted signs and symptoms of MYT1L Syndrome in children include:

• Developmental delays; delays in reaching milestones
• Excessive weight gain due to over-eating
• Intellectual disabilities and cognitive impairment
• Speech and learning disabilities is observed in almost all children
• Behavioral issues that may include challenging behavior
• Epileptic seizures, which may be observed in some children
• Some minor skeletal anomalies involving the limbs have been reported

In most cases, the physical growth and development of the child is not significantly affected.

How is MYT1L Syndrome Diagnosed?

Children can have varying signs and symptoms. Some children with mild signs and symptoms may go undiagnosed in their lifetimes. Given the rarity of the condition, the healthcare provider should have a high index of suspicion to consider MYT1L Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

MYT1L Syndrome is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation, including family medical history
• Assessment of the presenting signs and symptoms, including evaluation of body systems such as vision, hearing, muscles, heart, kidneys, central nervous system, genitalia, and immune system
• Laboratory tests, as needed, such as electrolyte levels, serum calcium levels, thyroid function test, kidney function test, urine tests, sex hormone studies, etc.
• Radiological studies of the affected regions, as needed
• Brain scans: These may include prenatal ultrasounds and MRI scans, and CT/MRI scans after development of the child
• Neurological examination that involves the central nervous system (brain and spinal cord)
• Behavioral studies
• Prenatal studies including abdominal ultrasonography
• Specialized genetic testing techniques are often required to confirm the diagnosis. This may include:
  • Fluorescence in situ hybridization (FISH) testing
  • Array comparative genomic hybridization (array-CGH)
  • DNA sequencing

Often, karyotyping of the chromosome is not adequate to diagnose the condition, since individuals with this condition can have normal karyotype chromosomal studies.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of MYT1L Syndrome?

The complications of MYT1L Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Delayed milestone achievement that may affect when a child rolls, sit, crawl, or walk; walking is noted to take place after about 24 months
• Some individuals may have significant mobility issues
• Childhood obesity
• Spinal cord defects (in very rare cases)
• Seizures causing fall injuries
• Mental health deficiencies (below average to low IQ levels)
• Autistic behavior may be observed in some cases, including attention-deficit hyperactivity disorder (ADHD)
• Overall reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is MYT1L Syndrome Treated?

There is no cure for MYT1L Syndrome since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. It also depends on the severity of the signs and symptoms and the body systems affected. Individuals with mild signs and symptoms may require periodic monitoring without significant medical intervention. Often, a multidisciplinary team of specialists including pediatricians, ophthalmologists, otolaryngologists, neurologists, internists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for MYT1L Syndrome may involve:

• Employing suitable learning strategies
• Speech and language therapy
• For feeding difficulties, medications, feed thickeners, bottle-feeding expressed milk, including special diets and nutritional supplements
• Seizure control using anticonvulsant medication, vitamin supplements, and ketogenic diet. Seizure control is important to ensure that the child’s learning ability is not significantly affected.
• Development of motor skills via daily exercises, swimming, and other adapted activities
• Use of walking aids
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Occupational therapy
• Social skills training support groups and exercises
• Lifestyle modification and dietary control, as applicable, for obesity

Regular medical screening at periodic intervals with tests and physical examinations are necessary and highly recommended.

How can MYT1L Syndrome be Prevented?

MYT1L Syndrome may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child. A majority of cases are sporadic occurrences, which means there is no family history of the condition.

In some rare cases, the condition may be familial, meaning they occur within families. In expecting parents with a familial history:

• Genetic (chromosome) testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of MYT1L Syndrome? (Outcomes/Resolutions)

The prognosis of MYT1L Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. It may be assessed on a case-by-case basis, but it is generally difficult to predict the long-term outlook.

• Children with mild conditions are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Children usually require lifelong medical support and care; it may also take some children a long time (several years) to gain a measure of independence

Additional and Relevant Useful Information for MYT1L Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/