MECP2 Duplication Syndrome is a progressive neurological disorder due to a chromosomal anomaly. The chromosomal disorder was first reported in 2005 and involves duplication of the methyl CpG binding protein 2 (MECP2) gene on the chromosome X.
MECP2 duplication syndrome primarily affects males, but females who carry the duplication on one X chromosome may exhibit some signs of the disorder.
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What causes MECP2 duplication syndrome?
MECP2 is a rare neurodevelopmental disorder caused by duplication of the MECP2 gene on X chromosome; other genes may also be involved, depending on the size of the duplicated segment.
The MECP2 gene is involved in the production of the MECP2 protein, which is a crucial element in regulating the function of the brain. Abnormalities in the production of this protein cause brain dysfunction and physical impairment.
What are the signs and symptoms of MECP2 duplication syndrome?
A wide variety of symptoms characterizes the MECP2 duplication syndrome:
- Weak muscle tone during infancy (infantile hypotonia) and feeding difficulties
- Moderate to severe intellectual disability
- Developmental delays and developmental regression
- Speech abnormalities
- Seizures – especially the tonic-clonic type which involves loss of consciousness, muscle rigidity, and convulsions
- Progressive muscle stiffness or spasticity
- Recurrent respiratory tract infections, which are a major cause of death in affected individuals
- Ataxia or wobbly movements
- Gastrointestinal symptoms such as heartburn, acid reflux, and severe constipation
How is MECP2 duplication syndrome diagnosed?
The diagnostic procedure begins with taking a complete medical history and the identification of the characteristic symptoms. This is followed by a thorough clinical evaluation and a variety of diagnostic tests.
Genetic testing using Array CGH (Comparative Genomic Hybridization) is commonly used to diagnose MECP2 duplication syndrome. Array CGH permits detection at sub-microscopic levels; hence, it is the best test for screening genetic disorders.
Whole exome or whole genome sequencing is used when array CGH is not feasible. Whole genome sequencing looks at the entire DNA sequence of the affected individual, whereas whole exome sequencing examines only the protein-coding region of genes in a genome.
Many other diagnostic techniques may be used to detect MECP2 Duplication Syndrome.
Polymerase chain reaction (PCR) helps to amplify and repeatedly copy sequences of DNA, which helps to analyze the various genetic changes better.
Fluorescence in situ hybridization (FISH) test helps to decode an individual’s karyotype or chromosomal makeup; the test can detect duplications or translocation abnormalities in chromosomes.
The Multiplex ligation-dependent probe amplification (MLPA) test can detect chromosomal deletions or duplications, point mutations, identify the methylation status of DNA, and even detect single nucleotide polymorphisms or SNPs.
Pre-implantation genetic diagnosis is sometimes offered to parents with a known genetic abnormality. The procedure helps to identify genetic abnormalities in the embryo before it is implanted in the uterine wall.
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What are the treatment options for MECP2 duplication syndrome?
The treatment of MECP2 duplication syndrome is decided on the basis of the specific symptoms present and is highly individualized. Treatment usually involves collaborative efforts by a team of specialists.
Before initiating treatment, the doctor educates the patients and his family regarding the potential benefits and risks of the treatment.
Often the treatment is symptomatic and supportive; occupational, physical, and speech therapy usually proves beneficial. Rehabilitative and behavioral therapy is commonly used. Augmentative communication devices are used in people with language disorders.
Additional therapies for MECP2 duplication syndrome depend upon the specific abnormalities present and generally follow standard guidelines.
In patients with feeding and swallowing difficulties, insertion of a feeding tube may be required to ensure nutritional support and to prevent aspiration.
Anticonvulsant drugs may be used for treating seizures. Inclusion of a ketogenic diet and implantation of a vagus nerve stimulator are also believed to confer benefits.
Due to the risk of developing contractures, spasticity warrants prompt action. Physical medicine and rehabilitation are recommended. Drugs to treat spasticity and muscle rigidity are usually ineffective; in fact, they worsen the condition.
Infections should be treated with appropriate antibiotics. Recurrent respiratory infections are usually severe and often require hospitalization and mechanical ventilation. Such individuals are also at an increased risk of developing pneumonia. Prophylactic antibiotics and immunoglobulin therapy are indicated in such cases.