Disease name: MECP2 Duplication Syndrome

ICD-10 Disease Code: Q98.9 - Sex chromosome abnormality, male phenotype, unspecified

ICD-10 Disease Group: Q98 - Other sex chromosome abnormalities, male phenotype, not elsewhere classified

MECP2 duplication syndrome is a rare genetic disorder that primarily affects males, leading to moderate to severe intellectual disability and developmental delays. Individuals with this syndrome often exhibit low muscle tone from infancy, feeding challenges, and restricted or absent speech. Many experience motor skill delays, such as delayed sitting and walking, and some experience developmental regression, losing previously acquired skills. Respiratory infections are common and often severe, significantly impacting life expectancy, with only half of affected individuals living beyond 25 years.

Disease onset is caused by a mutation in a gene essential for brain function, particularly in gene regulation and protein production. An additional copy leads to excess protein, disrupting normal neuronal activity and contributing to the syndrome's symptoms.

MECP2 duplication syndrome is caused by a duplication mutation on the X chromosome at Xq28, which results in an extra copy of the MECP2 gene. The size of the duplicated segment can vary widely but always includes the MECP2 gene, with other genes sometimes affected depending on the duplication size.

Although the exact prevalence remains unknown, over 200 cases of intellectual disability linked to the syndrome have been described. The disorder primarily affects males due to its X-linked inheritence pattern.

Symptoms vary but include significant developmental delays, intellectual disability and progressive muscle stiffness. Motor delays are common, with some children showing regression in childhood. Speech is often limited or absent, and behavioural symptoms such as hand movements, bruxism, and episodes of screaming or night laughing are frequent. Respiratory infections affect more than 75% of males with the syndrome and a significant proportion of females with the syndrome. Seizures, both epileptic and non-epileptic, are common, often requiring ongoing management. 

Other symptoms may include gastrointestinal issues, scoliosis, eye issues, and facial dysmorphia.

Management of MECP2 duplication syndrome is symptom-focused and multidisciplinary, involving nutritional support to prevent malnutrition, and measures to manage recurrent infections, particularly infections of the respiratory system.

Supportive care includes educational and rehabilitation resources tailored to the developmental and intellectual disabilities in question. Regular monitoring and treatment of seizures, respiratory infections, and gastrointestinal issues are integral to care, while physical therapies can help manage progressive muscle stiffness and mobility issues.

• https://www.icd10data.com/
• https://www.orpha.net/consor/cgi-bin/index.php
• https://rarediseases.org/
• https://medlineplus.gov/genetics/
• https://www.cdc.gov/

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MECP2 duplication syndrome