Juvenile Alexander Disease and Cleidocranial Dysplasia: A Rare Combination of Genetic Abnormalities in a Pediatric Patient

Abstract

Cleidocranial dysplasia (CCD) and Alexander disease (AxD) are rare, autosomal dominant disorders that are characterized by a mutation in the runt-related transcription factor 2 ( RUNX2) and the glial fibrillary acidic protein ( GFAP) genes, respectively. There is no known relationship between RUNX2 and GFAP which would cause co-morbidity. We report a rare case of a 13-year-old with CCD who came to the clinic complaining of a 2-year history of progressively worsening episodic exacerbations of bulbar, ataxia, nystagmus, kyphoscoliosis, and nausea, but was intact cognitively. Initial diagnosis was a difficult process because preliminary symptoms for Juvenile AxD overlapped with previously diagnosed CCD and the initial genetic test identified our patient’s GFAP gene as a variant of uncertain significance. Our experience emphasizes the importance of continuing to report pathogenic variants of GFAP for AxD to build on our existing compendium of variants for GFAP for quicker and more efficient diagnosis of AxD.