What Is MECP2 Duplication Syndrome?
MECP2 duplication syndrome is an uncommon genetic disorder that affects neurodevelopmental development. This syndrome is almost exclusively seen in males with moderate to severe intellectual disabilities. But very rarely, females carrying the duplication on one X chromosome may show some signs and symptoms of the condition. The cause of this syndrome is genetic material duplication in a specific region on the X chromosome.
This condition is characterized by a wide range of symptoms, including hypotonia (weak muscle tone), feeding difficulties, developmental delays in motor skills (the baby may find difficulty crawling, sitting, and walking., potentially severe intellectual disability, speech abnormalities, respiratory disorders, seizures, and muscle spasticity (abnormal muscle tightness that can worsen with movement).
About 50 percent of affected individuals have seizures, especially the tonic-clonic type, causing muscle rigidity, loss of consciousness, and convulsions. This type of seizure generally does not respond to medications. Developmental regression, meaning the loss of previously acquired skills, may also be noted in a few affected individuals. Most individuals with this condition have respiratory infections, and the severity of the condition may vary between individuals. Respiratory infections can be a major cause of death in many individuals.
What Is the Cause of MECP2 Duplication Syndrome?
MECP2 duplication syndrome is a genetic disorder caused by the presence of an extra copy of the MECP2 (methyl CpG binding protein 2) gene located on the X chromosome of each cell. This extra copy of the MECP2 gene occurs due to genetic material duplication present on the long arm of the X chromosome. The duplication size can vary in individuals from 100,000 to some million DNA (deoxyribonucleic acid) building blocks.
The main gene involved in the duplication is the MECP2 gene, while a few other genes may also get involved sometimes, depending on the size of the duplicated segment. However, the role of extra copies of the other genes in affecting the severity of the condition needs to be better understood.
The MECP2 gene carries instructions for producing a protein called MeCP2 (methyl CpG binding protein 2). MeCP2 protein is an essential protein for normal brain function and several different functions in the body. The main other functions of the gene include regulating other genes in the brain by tuning them when they can engage in protein production. When there is an extra copy of the MECP2 gene, it will produce more MeCP2 protein, leading to an increase in protein function. The sudden excess of protein production in the brain will cause abnormalities in nerve cell function. These changes in nerve cell function can confuse normal brain activity, leading to signs and symptoms of MECP2 duplication syndrome.
What Are the Signs and Symptoms of MECP2 Duplication Syndrome?
MECP2 duplication syndrome is characterized by a wide range of symptoms. As there are various symptoms, the core characteristic signs and symptoms are unclear.
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Hypotonia - It is a condition causing weak muscle tone. The initial notable sign of this syndrome is difficulty feeding. This sign may be evident in the first few weeks. Affected infants may also experience difficulty swallowing, excessive drooling, and gastroesophageal reflux. Due to all these feeding difficulties, the child may not gain weight compared to normal infants. They also have aspiration issues.
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Delay in Developmental Milestones - Some babies may not show recognized problems immediately after birth, but they may show delays in developmental milestones, including crawling, sitting, standing, and walking. Some infants possess unsteady and uncoordinated walking patterns.
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Cognitive Disability - Individuals with MECP2 duplication syndrome will have moderate to severe cognitive disability, including social and practical skills, such as language, conceptual, and social and self-care skills.
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Hyperlordosis - This is a condition causing excessive curves of the lower spine and creating a C-shaped curvature appearance of the lower spine. This abnormal gait can contribute to the development of inward curvature in the lower spine.
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Neurological Regression - As affected individuals grow older, about 50 percent may experience loss of previously acquired skills such as speaking skills, ability to walk, and others. Generally, the onset of neurological regression is associated with the onset of epilepsy.
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Speaking Disability - Most individuals affected by this condition do not develop the ability to talk. Few infants may be able to speak some words during early childhood, but speaking ability is generally progressively lost during adolescence.
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Muscle Spasticity - It is a condition causing an abnormal increase in muscle tone or stiffness. Spasticity can be linked to muscle spasms, fixed joints, and increased deep tendon reflexes. In many cases, hypotonia may progress to muscle spasticity. This condition more commonly affects the lower limbs. Other body parts like hips, knees, and ankles may also have mild to severe spasticity.
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Epilepsy - About 50 percent of the affected population will develop epilepsy in childhood or adolescence. A seizure attack can become more prevalent by adulthood. The type of seizures reported in individuals with MECP2 duplication syndrome are absence seizures, head or neck, and trunk drop attacks, generalized or secondarily generalized tonic-clonic, myoclonic seizures, and/or simply tonic seizures.
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Recurrent Infection - MECP2 Duplication Syndrome can cause immune system dysfunction so that the affected individuals may be prone to recurrent infections like urinary tract infections, respiratory tract infections, middle ear infections, and others.
What Is the Diagnosis and Treatment for MECP2 Duplication Syndrome?
MECP2 duplication syndrome is diagnosed based on checking characteristic symptoms, clinical investigations, taking a complete patient history, and various tests.
There is no cure for MECP2 duplication syndrome. Treatments are based on the presenting symptoms, which help to alleviate the child's symptoms and provide a better quality of life.
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Feeding Tube: Supplemental food from a feeding tube will be provided for infants facing feeding difficulties.
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Physical Therapy: This helps improve muscle strength, mobility, and flexibility and prevents joint contractures.
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Speech Therapy: It helps to develop the patient's speaking skills.
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Medications: Depending on the presenting illnesses and complications, medications may be required to relieve pain and improve the patient's immunity.
Conclusion:
MECP2 duplication syndrome is a rare genetic cause due to the presence of an extra copy of the MECP2 gene located on the X chromosome of each cell. The affected individuals will experience a variety of signs and symptoms, like epilepsy, hypotonia, feeding difficulties, recurrent infections, developmental delays, and neurological issues. As this is a genetic disorder, a permanent cure is not possible. The treatment aims to alleviate the presenting illnesses and improve the quality of patient's lives.
