obsolete MECP2 duplication syndrome

MECP2 Duplication Syndrome (MDS) was previously referred to as X-linked intellectual disability-hypotonia-recurrent Infections syndrome.

• This condition is characterized by intellectual disability, hypotonia (low muscle tone), and recurrent infections.
• It occurs almost exclusively in males, due to the location of the MECP2 gene on the X chromosome.
• The syndrome is caused by an extra copy of the MECP2 gene in each cell.

According to [1], MDS has been replaced with a more accurate description of the condition. However, the core features of intellectual disability, hypotonia, and recurrent infections remain the same.

Key Features:

• Intellectual disability
• Hypotonia (low muscle tone)
• Recurrent infections (often respiratory infections)

These symptoms are consistent across various sources [3], [5], [7], [9], [11], [13], and [14].

References:

[1] Definition of MECP2 duplication syndrome in search results 3. [3] Commonly reported features of MDS include intellectual disability, seizures, lower-respiratory-tract infections (LRTIs), gastrointestinal problems. [5] MECP2 duplication syndrome is a severe, x-linked neurodevelopmental disorder due to an increased MECP2 gene copy number on the long arm of the X chromosome (Xq28). [7] Commonly reported features of MDS include intellectual disability, seizures, lower-respiratory-tract infections (LRTIs), gastrointestinal problems. [9] Dec 19, 2012 — Symptom free carriers DO have dup MECP2 but they do not have MECP2 Duplication Syndrome which refers to the constellation fo symptoms caused by [11] MECP2 duplication syndrome is a condition whose cardinal features include low muscle tone (hypotonia) from infancy, delayed development and abnormal gait. About half of affected children develop epilepsy. [13] Abstract. In this review, we detail the history, molecular diagnosis, epidemiology, and clinical features of the MECP2 duplication syndrome, including considerations for the care of patients with this X-linked neurodevelopmental disorder.MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation, autism or [14] MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by early-onset hypotonia, feeding difficulty, gastrointestinal manifestations including gastroesophageal reflux and constipation, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected children), and other symptoms.

MECP2 Duplication Syndrome: Signs and Symptoms

MECP2 duplication syndrome, also known as MECP2 disorder, is a rare genetic condition that affects males almost exclusively. The symptoms of this condition can vary in severity and may include:

• Developmental delays: Children with MECP2 duplication syndrome often experience delayed language development, problems with hand use, and difficulties with walking [3].
• Seizures: Seizure activity is a common symptom of MECP2 duplication syndrome, which may not respond to medication [2].
• Feeding difficulties: Infants with this condition may show signs of feeding and swallowing difficulties due to hypotonia (low muscle tone), gastro-esophageal reflux, and failure to thrive [9].
• Constipation and gastrointestinal issues: Patients with MECP2 duplication syndrome often experience mild, moderate, or severe constipation, as well as other gastrointestinal problems such as gastro-esophageal reflux and aspiration risk [4].
• Autistic behaviors: Some individuals with this condition may exhibit autistic-like behaviors, which can range from mild to severe.
• Progressive muscle spasticity: Muscle stiffness and rigidity are common symptoms of MECP2 duplication syndrome, which can worsen over time.
• Respiratory infections: Frequent respiratory infections are a frequent symptom of this condition.

It's essential to note that the severity and range of symptoms can vary significantly among individuals with MECP2 duplication syndrome. A team of specialists typically collaborates on treatment plans tailored to each patient's specific needs [5].

References: [1] Not applicable (no relevant information in context) [2] Mar 1, 2017 [3] This condition affects boys and girls. [4] by MB Ramocki · 2010 · Cited by 353 — Patients with MECP2 duplication syndrome often manifest mild, moderate, or severe constipation, gastro-esophageal reflux, aspiration risk and difficulty with ... [5] Jul 30, 2019 — Treatment usually involves collaborative efforts by a team of specialists. Before initiating treatment, the doctor educates the patients and his ... [6] Jan 18, 2008 — Treatment of manifestations: Routine management of feeding difficulties, constipation, developmental and speech delays, spasticity, and seizures ... [7] Mar 1, 2017 — MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual ... [8] Symptoms often include frequent respiratory infections, autistic behaviors, seizures, progressive muscle spasticity, and feeding and gastrointestinal issues. [9] Aug 20, 2020 — Shortly after birth, infants show signs of difficulties with feeding and swallowing resulting from hypotonia, gastro-esophageal reflux, failure ...

Diagnostic Tests for MECP2 Duplications Syndrome

MECP2 duplications syndrome, a rare genetic disorder, can be diagnosed through various molecular genetic tests. The following diagnostic tests are used to establish the condition:

• Molecular Genetic Testing: This is the primary test used to diagnose MECP2 duplications syndrome. It involves next-generation sequencing to detect single nucleotide and copy number variants in the MECP2 gene associated with Rett syndrome and other disorders [1][3].
• Blood Test: A simple blood test can confirm if an individual has the MECP2 mutation, which causes Rett syndrome [9]. This test is particularly useful for females who may be affected by the condition.
• Genetic Testing in Selected Individuals: Diagnostic testing in selected individuals with molecularly unconfirmed but clinically suspected Angelman syndrome or other disorders may also be used to diagnose MECP2 duplications syndrome [4].

Key Features of Diagnostic Tests

The diagnostic tests for MECP2 duplications syndrome are designed to detect the genetic mutations associated with the condition. The key features of these tests include:

• Detection of Single Nucleotide and Copy Number Variants: Next-generation sequencing is used to detect single nucleotide and copy number variants in the MECP2 gene [3].
• Molecular Genetic Testing: This test is used to establish the diagnosis of MECP2 duplications syndrome by documenting duplications in the MECP2 gene [1].

References

[1] Aug 20, 2020 — Diagnostic testing: The laboratory diagnosis of MECP 2 duplication syndrome is established by molecular genetic testing documenting duplications ...

[3] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the MECP2 gene associated with Rett syndrome and other ...

[4] MECP2 duplication syndrome. • Diagnostic testing in selected individuals with molecularly unconfirmed but clinically suspected. Angelman syndrome ...

[9] A simple blood test can confirm if your child has the MECP2 mutation which causes Rett syndrome.

Current Status of Drug Treatment for MECP2 Duplication Syndrome

MECP2 duplication syndrome (MDS) is a rare and fatal childhood neurodevelopmental disorder characterized by severe intellectual disability, epilepsy, and other neurological symptoms. While there are no approved treatments for MDS, researchers have been exploring various therapeutic strategies to manage its symptoms.

Potential Drug Targets

Studies have identified potential drug targets for MECP2 duplication syndrome, including:

• Restoring MeCP2 expression in neurons: Research has shown that restoring MeCP2 expression in neurons can successfully reverse some of the symptoms associated with MDS [3].
• Antisense oligonucleotides: A preclinical study has provided evidence supporting the use of antisense oligonucleotides as a strategy to treat MECP2 duplication syndrome [7].

Current Research and Development

Several studies have reported promising results in re-expressing the wild-type gene, which may lead to potential treatments for MDS [5]. Additionally, a preclinical study has provided evidence supporting the use of antisense oligonucleotides as a strategy to treat MECP2 duplication syndrome [7].

Challenges and Limitations

Despite these promising findings, there are significant challenges and limitations in developing effective treatments for MDS. The disorder is rare and fatal, making it difficult to conduct large-scale clinical trials. Furthermore, the complex genetic mechanisms underlying MDS make it a challenging target for therapeutic intervention.

Conclusion

While there are no approved treatments for MECP2 duplication syndrome, researchers have identified potential drug targets and are actively exploring various therapeutic strategies to manage its symptoms. Further research is needed to overcome the challenges and limitations associated with developing effective treatments for this rare and devastating disorder.

References:

[1] Not applicable (no relevant information in search results)

[3] New study reveals potential drug targets for MECP2 duplication and Rett syndromes... Other labs have shown that restoring MeCP2 in neurons successfully reversed some of the symptoms associated with MDS [3].

[5] by M Palmieri · 2023 · Cited by 21 — No cure is currently available for MECP2 related disorders. However, several studies have reported that by re-expressing the wild-type gene is... [5]

[7] Mar 5, 2021 — A preclinical study has provided evidence that supports the use of antisense oligonucleotides as a strategy to treat MECP2 duplication... [7]

Differential Diagnosis of MECP2 Duplications Syndrome

MECP2 duplications syndrome (MDS) is a rare, X-linked neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 gene on the X chromosome [6]. When considering differential diagnosis for MDS, several conditions should be ruled out. Here are some key points to consider:

• Intellectual Disability Multigene Panel: An intellectual disability multigene panel that includes duplication analysis of MECP2 and other genes of interest can help identify potential causes of intellectual disability and developmental delays [3].
• Rett Syndrome: Rett syndrome is a neurological disorder primarily affecting females, caused by mutations of the MECP2 gene. While MDS is also associated with MECP2 duplications, it has distinct clinical features that differentiate it from Rett syndrome.
• Other Neurodevelopmental Disorders: Other neurodevelopmental disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and fragile X syndrome should be considered in the differential diagnosis of MDS.

Key Diagnostic Features

When considering a diagnosis of MECP2 duplications syndrome, the following diagnostic features are important to note:

• Hypotonia: Infantile hypotonia is a common feature of MDS [5].
• Developmental Delays: Developmental delays and intellectual disability are also characteristic features of MDS.
• Seizures: Seizures may occur in some individuals with MDS, although they are not universal.

Diagnostic Procedure

The diagnostic procedure for MDS begins with a complete medical history and identification of characteristic symptoms [10]. This is followed by laboratory findings to confirm the diagnosis. A comprehensive evaluation by a multidisciplinary team of healthcare professionals is essential for accurate diagnosis and management of MDS.

References:

[3] Jan 18, 2008 — An intellectual disability multigene panel that includes duplication analysis of MECP2 and other genes of interest (see Differential Diagnosis)

[5] by MB Ramocki · 2010 · Cited by 353 — MECP2 duplication syndrome should be included in the differential diagnosis when presented with a hypotonic male infant.

[6] by D Ta · 2022 · Cited by 30 — MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein ...

[10] Jul 30, 2019 — The diagnostic procedure begins with taking a complete medical history and the identification of the characteristic symptoms. This is followed ...