An adult patient with Tatton–Brown–Rahman syndrome caused by a novel DNMT3A variant and axonal polyneuropathy

Abstract

Tatton–Brown–Rahman syndrome (TBRS) is a rare autosomal dominant overgrowth syndrome first reported in 2014 and caused by pathogenic variants in the DNA methyltransferase 3A (DNMT3A) gene. All individuals reported to date share a phenotype of somatic overgrowth, dysmorphic features, and intellectual disability. Peripheral neuropathy was not described in these cases. We report an adult patient with TBRS caused by a novel pathogenic DNMT3A variant (NM_175629.2: c.2036G>A, p.(Arg688His)) harboring an axonal length‐dependent sensory‐motor polyneuropathy. Extensive laboratory and molecular genetic work‐up failed to identify alternative causes for this patient's neuropathy. We propose that axonal neuropathy may be a novel, age‐dependent phenotypic feature in adults with TBRS and suggest that this syndrome should be considered in the differential diagnosis of patients with overgrowth, cognitive and psychiatric difficulties, and peripheral neuropathy.