A Heterozygous Variant in the GABBR2 Gene in a Girl With Clinical Classic Rett Syndrome.
Jenny Klintenstedt, Peter Baeck, Ingegerd Witt Engerström et al.
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Case in brief
A girl diagnosed with classic Rett syndrome exhibited developmental stagnation, loss of purposeful hand use, stereotypic movements, autonomic dysfunction, and behavioral issues. Standard genetic tests for MECP2 and CDKL5 were negative. Whole-exome sequencing revealed a heterozygous de novo variant in the GABBR2 gene, which was confirmed by Sanger sequencing, providing a genetic explanation for her symptoms.
What made this case unusual
The identification of a GABBR2 variant in a patient with classic Rett syndrome, despite negative results for the more commonly implicated MECP2 and CDKL5 genes, highlights an atypical genetic cause.
Diagnostic / clinical pearl
Clinicians should consider GABBR2 variants in the genetic evaluation of patients with a clinical phenotype of Rett syndrome, especially when MECP2 and CDKL5 testing is negative.
Why it matters
This case underscores the need for comprehensive genetic testing in Rett syndrome, as it may reveal alternative genetic causes that influence diagnosis and management.