Rett syndrome

Rett syndrome is a rare genetic disorder that affects brain development, resulting in severe mental and physical disability [3]. It is characterized by a slowing of development after typical early growth and development [2].

The hallmark of Rett syndrome is near constant repetitive hand movements while awake [1][5]. Cognitive assessment in children with Rett syndrome is complicated, but it often causes developmental delays or trouble with movement [7].

Rett syndrome may cause speech difficulties, loss of spoken language, and motor skills problems, as well as behavioral and neurological issues [4][8]. It is almost exclusively seen in females, although rare cases in males have been reported [6].

The disorder is caused by mutations in the MECP2 gene on chromosome X, which affects all body movement and can lead to severe physical disability [9]. Overall, Rett syndrome is a progressive neurodevelopmental disorder that requires early diagnosis and intervention for optimal management.

Early Signs and Symptoms

Rett syndrome is characterized by a range of symptoms that can vary in severity and progression. The first signs often include:

• Reduced hand control [1]
• Decreasing ability to crawl or walk [1]
• Loss of muscle tone, called hypotonia [6]

As the condition progresses, other symptoms may become apparent, including:

• Loss of speech [2][9]
• Loss of purposeful use of hands [2]
• Involuntary hand movements such as handwashing [2]
• Loss of mobility or gait disturbances [3][9]
• Slowing of development [3]
• Distinctive hand movements [3]
• Slowed brain and head growth [3]
• Problems with communication and cognitive abilities [5]

Other signs and symptoms may include:

• Developmental delays or stagnation [8]
• Loss of eye contact [8]
• Lack of interest in normal play and interactions [8]
• Slowing of head growth [7]
• Rapid breathing [7]
• Trouble moving or coordinating movements [7]
• Balance problems [9]
• Breathing problems [9]

Important Notes

It's essential to note that many children with Rett syndrome show few to no symptoms in their first year of life, and then development slows as they get older [4]. Early diagnosis is crucial for providing the best possible care and support.

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9

Diagnostic Tests for Rett Syndrome

Rett syndrome, a rare genetic disorder, can be diagnosed through various tests that evaluate the presence of specific mutations in the MECP2 gene and other genes associated with the condition.

• Genetic Testing: A blood test or genetic evaluation can identify whether a child has one of the known mutations that cause Rett syndrome [1]. This test can also detect mutations in other genes, including CDKL5 and FOXG1, which are linked to atypical types of the disease [5].
• MECP2 Gene Mutation: A genetic test may detect a disease-causing change within the MECP2 gene, which is found in most people with a clinical diagnosis of Rett syndrome (80-97%) [6]. However, even if a MECP2 variation is found, the child may not be diagnosed with Rett syndrome if they don't fit the clinical diagnostic criteria.
• Clinical Diagnostic Criteria: A clinical diagnosis of Rett syndrome can be made by fulfilling specific diagnostic criteria, which include symptoms such as progressive inability to use muscles for eye and body movements and language [4]. Molecular genetic testing can detect the presence of mutations of the MECP2 gene and confirm the clinical diagnosis [11].
• Blood Test: A simple blood test can confirm the presence of the MECP2 mutation, but it is not enough for a diagnosis of Rett syndrome. It also requires a clinical diagnosis based on observed signs and symptoms [15].

References

[1] Jan 18, 2022 — Blood Test [4] May 3, 2022 - This rare genetic disorder affects the way the brain develops... [5] January 18, 2022 - A genetic test also can be used to detect mutations in other genes... [6] This genetic test may detect a disease-causing change within the MECP2 gene. [11] November 20, 2023 - The fulfillment of these diagnostic criteria can lead to a clinical diagnosis... [15] December 19, 2023 - A blood test can confirm the presence of the MECP2 mutation...

Treatment Options for Rett Syndrome

Rett syndrome, a rare genetic neurological disorder, has limited treatment options. However, recent advancements have led to the approval of a new drug treatment.

• Trofinetide (Daybue): The first and only FDA-approved treatment for Rett syndrome in children aged 2 years or above [3]. This oral solution has been shown to significantly improve symptoms from the perspective of both caregivers and clinicians [6][9].
• Mechanism of Action: Trofinetide targets the specific pathway for the MECP2 gene mutation, reducing inflammation in the brain. It works by modulating the expression of genes involved in the disease process [4].

Other Treatment Options

While there is no cure for Rett syndrome, certain comorbidities associated with the disorder can be treated. Medications such as anticonvulsants and benzodiazepines may be prescribed to manage seizures and anxiety [8].

Future Developments

Research continues to explore new treatment options for Rett syndrome. Investigational drugs, including medical cannabinoid drug therapy, are being studied for their potential benefits in treating the disorder [7].

Differential Diagnoses for Rett Syndrome

Rett syndrome (RS) can be challenging to diagnose, and it often requires a comprehensive evaluation to rule out other conditions that may present with similar symptoms. The differential diagnosis for RS varies depending on the clinical stage of the disorder.

Common Differential Diagnoses:

• Autism: Infantile autism is the most common incorrect diagnosis made for children with RS [3].
• Cerebral Palsy: Cerebral palsy can be a differential diagnosis, particularly in cases where there are motor dysfunction and developmental delays.
• Angelman Syndrome: This rare genetic disorder characterized by severe developmental delays and intellectual disability should be considered in the differential diagnosis of RS.
• Non-Specific Developmental Delay: Children with RS may initially present with non-specific developmental delay, making it essential to monitor their progress and adjust the diagnosis accordingly.

Other Differential Diagnoses:

• Hearing or Vision Problems: Hearing or vision impairments can be mistaken for symptoms of RS.
• Degenerative Disorders: Certain degenerative disorders that cause motor dysfunction and language regression may also be considered in the differential diagnosis.

Clinical Staging and Differential Diagnosis

The differential diagnosis for RS varies depending on the clinical stage of the disorder. As the disease progresses, it is essential to consider other conditions that may present with similar symptoms [6].

References:

• [1] Mar 20, 2023 — Diagnostic criteria.
• [2] by G Chahil · 2023 · Cited by 24 — Important differential diagnoses to consider are cerebral palsy, autism, Angelman syndrome, and non-specific developmental delay.
• [3] by E Trevathan · 1988 · Cited by 138 — Infantile autism is the most common incorrect diagnosis made for children with RS.
• [4] The disorder has a progressive clinical course and may associate various comorbidities including gastrointestinal diseases, scoliosis, and behavioral disorders.
• [5] Differential Diagnosis[edit | edit source]
• [6] Mar 20, 2023 — Diagnosis of Rett syndrome​​ The differential diagnosis varies according to the clinical stage of RS.