MECP2-Duplikationssyndrom: MedlinePlus Genetics (2023)

FAQs

What is the MECP2 genetic condition? ›

MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, or muscle stiffness (rigidity).

The syndrome is caused by having an extra copy (duplication) of the MECP2 gene, and inheritance is X-linked. The syndrome almost always occurs in males (who have one X chromosome), but some females with the duplication on one of their two X chromosomes have some signs or symptoms.

Most affected males inherit the disorder from a carrier mother who has favorable survival of the X-chromosome carrying the one normal copy of MECP2 as the active X chromosome. Such carrier females either have no symptoms or extremely mild symptoms such as anxiety or mild symptoms of the disorder.

Rett syndrome (RTT) is a neurodevelopmental disorder caused predominantly by loss-of-function mutations in the gene Methyl-CpG-binding protein 2 (MECP2), which encodes the MeCP2 protein. RTT is a MECP2-related disorder, along with MECP2 duplication syndrome (MDS), caused by gain-of-function duplications of MECP2.

The genetic disorder means he will likely start suffering from seizures around the age of five, which will eventually cause his brain to stop functioning normally. The condition was discovered in 2005 and has a life expectancy of about 25 years old.

Mutations in the MECP2 gene have been found to cause PPM-X syndrome. This disorder is characterized by mild to severe intellectual disability, bipolar disorder, and a pattern of movement abnormalities known as parkinsonism.

Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene—a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000.

In 1999, NICHD-supported scientists discovered that most classic Rett syndrome cases are caused by a mutation within the Methylcytosine-binding protein 2 (MECP2) gene. The MECP2 gene is located on the X chromosome. Between 90% and 95% of girls with Rett syndrome have a mutation in the MECP2 gene.

In females (who have two X chromosomes), a duplication of one of the two copies of the gene typically does not cause the disorder, but can be associated with behavioral and psychiatric symptoms such as depression, anxiety, and features of autism spectrum disorder that affect communication and social interaction.

Is Rett syndrome genetic or chromosomal? ›

Although Rett syndrome is a genetic disorder, less than 1% of recorded cases are passed from one generation to the next. Most cases are spontaneous, which means the mutation occurs randomly. However, in some families of individuals affected by Rett syndrome, other family members have a mutation in the MECP2 gene.

The MECP2 gene is located on the X chromosome, and RTT is classified as an X-linked dominant disorder. Thus, as expected, males are more severely affected and rarely survive infancy.

On average, most individuals with the condition survive into their 40s or 50s.

'Ann-Charlotte “Lottan” Holmström is most probably the oldest person with Rett Syndrome in Sweden and in all likelihood one of the oldest in the world.

MECP2 mutations lead to Rett syndrome in females. Incomplete penetrance is observed. Clinical features include developmental arrest 6-18th month of life, epileptic seizures, intellectual disability, ataxia, microcephaly, and typical hand-washing stereotypic movements.

Single genes can be replicated through the action of transposable elements, slippage during DNA replication, or unequal crossing during meiosis, whereas whole genomes can be duplicated via accidents in meiosis (autopolyploidization) or hybridization between distinct taxa (allopolyploidization).

Gene duplications are an essential source of genetic novelty that can lead to evolutionary innovation. Duplication creates genetic redundancy and if one copy of a gene experiences a mutation that affects its original function, the second copy can serve as a 'spare part' and continue to function correctly.

The rates of gene duplication in these model species are estimated at between 0.2% and 2% per gene per million years (5, 6).

Therefore, in the vast majority of cases Rett syndrome is not an inherited disorder. In such cases, the parents have normal chromosomes and the mutation arises in one of the parent's reproductive (germ) cells, usually on the paternal side.

Most affected children are diagnosed with an intellectual disability. The current treatment approach for Rett syndrome focuses on managing symptoms, improving movement and communication, and supporting patients and their families.

Does Rett syndrome show up on genetic testing? ›

If your child's health care provider suspects Rett syndrome after evaluation, genetic testing (DNA analysis) may be needed to confirm the diagnosis. The test requires drawing a small amount of blood from a vein in your child's arm.

Rett syndrome patients are fertile but unlikely to have children. Therefore the mutations are rapidly lost from the human gene pool. More than 60 mutations have been identified that cause Rett syndrome.

Rett syndrome is a rare genetic disorder that affects brain development, resulting in severe mental and physical disability. It's estimated to affect around 1 in 10,000 girls born each year and is only rarely seen in boys.

Rett Syndrome (RTT) is a rare neurodevelopmental disorder which is seen almost exclusively in females and more rarely in males. It is estimated to occur in 1 in 10,000 female births across all racial and ethnic groups.

Genetic testing can be used to aid in or confirm a patient's diagnosis of Rett syndrome, a progressive neurodevelopmental condition that affects females almost exclusively. It also can be used in pregnancy screenings to enable a prenatal diagnosis.

Rett syndrome is almost exclusively a disease that affects girls (XX), yet is not a disease with epigenetic inheritance, such as Prader-Willi syndrome and Angelman syndrome, where the clinical outcome depends on whether a mutation is transmitted from a paternal or maternal chromosome, and RTT mutations are not ...

Diagnosis/testing.

The diagnosis of MECP2 duplication syndrome is established in an individual by identification of a heterozygous whole-gene duplication of MECP2 on molecular genetic testing.

How Many People Have Rett Syndrome? It is estimated that one in 10,000 girls is born with Rett syndrome. This means about 15,000 girls and women in the US and 350,000 worldwide have the disorder.

On average, most individuals with the condition survive into their 40s or 50s.

Children with Rett syndrome typically begin to lose the ability to speak, to make eye contact and to communicate in other ways. They may become disinterested in other people, toys and their surroundings. Some children have rapid changes, such as a sudden loss of language.

How rare is MECP2 syndrome? ›

MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene—a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000.

MECP2-related severe neonatal encephalopathy is a neurological disorder that primarily affects males and causes brain dysfunction (encephalopathy). Affected males have a small head size (microcephaly ), poor muscle tone (hypotonia) in infancy, movement disorders, rigidity, and seizures.

In nearly all cases, the genetic change that causes Rett syndrome is spontaneous, meaning it happens randomly. Such random mutations are usually not inherited or passed from one generation to the next. However, in a very small percentage of families, Rett mutations are inherited and passed on by female carriers.

Although Rett syndrome is a genetic disorder, less than 1% of recorded cases are passed from one generation to the next. Most cases are spontaneous, which means the mutation occurs randomly. However, in some families of individuals affected by Rett syndrome, other family members have a mutation in the MECP2 gene.

Most affected children are diagnosed with an intellectual disability. The current treatment approach for Rett syndrome focuses on managing symptoms, improving movement and communication, and supporting patients and their families.

A diagnosis of Rett syndrome may not be made straight away because the syndrome is so rare, and symptoms do not tend to appear until a child is between 6 and 18 months old.

The syndrome is mainly caused by mutations in the MECP2 gene located on the X chromosome and whose function includes regulating the activity of many other genes. Because males have only one X chromosome, this means that a mutation in the MECP2 gene cannot be compensated by a healthy gene copy.

In Klinefelter syndrome, males have two copies of the X chromosome and one copy of the Y chromosome; thus, they have an extra chromosome giving them a chromosomal designation of 47, XXY. Klinefelter syndrome is relatively common, appearing in roughly 1 in 500 males.