Medical Biases and Misconceptions Impact Diagnoses in Males With Loss of Function MECP2 Variants
1Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado, USA.
Related Experiment Videos
View abstract on PubMed
Summary
Males with Rett syndrome (RTT), caused by MECP2 gene variants, face diagnostic delays due to medical biases. Earlier diagnosis is improving, but guidance for affected males remains insufficient.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Rare Diseases
Background:
- Rett syndrome (RTT) is a rare neurodevelopmental disorder.
- Typically caused by methyl-CpG binding protein-2 (MECP2) gene variants.
- Historically, MECP2 variants were considered non-viable in males, but clinical heterogeneity is now recognized.
Purpose of the Study:
- To enhance understanding of the diagnostic journey for males with confirmed pathogenic MECP2 alterations.
- To identify factors contributing to diagnostic delays and their impact.
- To address the lack of male-specific guidance in Rett syndrome.
Main Methods:
- International survey of caregivers (N=47) regarding diagnostic experiences.
- Phenomenological interviews with caregivers (n=32).
- Multivariate analysis to assess factors influencing age of diagnosis.
Main Results:
- Median age of genetic diagnosis was 3 years.
- Age of diagnosis decreased by 0.31 years for each year increase in birth year.
- Medical biases and misconceptions significantly delay accurate clinical diagnosis.
Conclusions:
- Increasing availability of genetic testing is reducing diagnostic age.
- Providers need greater awareness of MECP2 alterations in males.
- There is a critical need for improved anticipatory guidance and clinical recommendations for males with RTT.