Differences between typical Rett syndrome and its atypical counterpart.
Rett syndrome and its atypical counterpart are rare genetic neurodevelopmental disorders that primarily affect females. Affecting an estimated 1 in 10,000 females by the age of 12 years in the United States, these conditions are caused by mutations in specific genes and present with distinct symptoms and diagnostic criteria.
Symptoms
Typical Rett Syndrome
Typical Rett syndrome is characterized by normal early growth and development for the first 6-18 months, followed by a slowing down in development, loss of purposeful hand skills, and distinctive repetitive hand movements such as wringing or washing. Severe motor impairments, including apraxia (difficulty performing motor tasks), loss of speech, slowed head growth, seizures, and breathing abnormalities while awake (apnea, hyperventilation) are common. The condition progresses through four well-defined stages, including early onset, rapid regression, plateau, and late motor deterioration stage.
Atypical Rett Syndrome
Atypical Rett syndrome often presents with a less classic or incomplete presentation than typical Rett. Clinical signs can be variable and do not always follow the classic staged progression. The symptoms may be milder or delayed, and the individual may show some preserved abilities compared to typical Rett. Additionally, the condition can overlap with other neurodevelopmental disorders.
Causes
Both typical and atypical Rett syndromes are primarily caused by mutations in the MECP2 gene. Typical Rett syndrome is strongly linked to specific MECP2 mutations that produce the classic phenotype. Atypical Rett may result from different mutations or genetic variants in MECP2 that cause milder or variant phenotypes. The genetic basis can be more complex in atypical cases, with other genes or mosaicism potentially involved, creating overlapping or atypical symptoms.
Diagnostic Criteria
A diagnosis of typical Rett syndrome is made if an individual meets all main clinical criteria, including normal early development followed by regression, loss of purposeful hand skills, stereotypic hand movements, loss of acquired spoken language, gait abnormalities and characteristic breathing disturbances, and head growth deceleration.
Diagnosis of atypical Rett syndrome is more complex, as the individual may not meet all criteria for typical Rett. Diagnosis is supported by identifying MECP2 mutations but clinical presentation is incomplete or variant. Atypical Rett may be diagnosed when the clinical course or symptom profile deviates from the typical four-stage progression or symptom severity.
In summary, typical Rett syndrome presents with a well-characterized symptom progression after normal early growth, strongly linked to classical MECP2 mutations, and clear diagnostic criteria. Atypical Rett syndrome involves variable and milder symptoms, possibly different or partial MECP2 mutations, and lacks the full classical clinical picture, making diagnosis more challenging and reliant on genetic testing and clinical judgement.
- The medical-condition known as Rett syndrome, along with its atypical counterpart, are neurological disorders that primarily impact females, with one in every 10,000 females being affected by the age of 12 years in the United States.
- These developmental disorders, caused by mutations in specific genes, are characterized by a slowdown in development, loss of hand skills, and distinctive hand movements for typical Rett syndrome. Atypical Rett syndrome can present differently with symptoms that are less classical or incomplete.
- The science behind Rett syndrome indicates that both typical and atypical forms are primarily caused by mutations in the MECP2 gene, although the genetic basis can be more complex in atypical cases, potentially involving other genes or mosaicism.
- In health-and-wellness terms, the diagnostic criteria for typical Rett syndrome involve specific symptoms and clinical markers, while the diagnostic process for atypical Rett syndrome can be more complex due to variability in symptoms and the need for genetic testing and clinical judgment.
