%0 Case Reports
%T Rett syndrome diagnostic odyssey: Limitations of NextGen sequencing.
%A Abbott M
%A Angione K
%A Forbes E
%A Stoecker M
%A Saenz M
%A Neul JL
%A Marsh ED
%A Skinner SA
%A Percy AK
%A Benke TA
%J Am J Med Genet A
%V 0
%N 0
%D 2024 May 22
%M 38775384
%F 2.578
%R 10.1002/ajmg.a.63725
%X Typical (or classic) Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by a period of regression, partial or complete loss of purposeful hand movements, and acquired speech, impaired gait, and stereotyped hand movements. In over 95% of typical RTT, a pathogenic variant is found in the methyl-CPG binding protein 2 gene (MECP2). Here, we describe a young woman with clinically diagnosed typical RTT syndrome who lacked a genetic diagnosis despite 20 years of investigation and multiple rounds of sequencing the MECP2 gene. Recently, additional genetic testing using next-generation sequencing was completed, which revealed a partial insertion of the BCL11A gene within exon 4 of MECP2, resulting in a small deletion in MECP2, causing likely disruption of MeCP2 function due to a frameshift. This case demonstrates the ever-changing limitations of genetic testing, as well as the importance of continual pursuit of a diagnosis as technologies improve and are more widely utilized.