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

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.

Effect of local versus remote tonic heat pain during training on acquisition and retention of a finger-tapping sequence task.

Although pain is present in a large proportion of patients receiving rehabilitation, its impact on motor learning is still unclear, especially in the case of neuropathic pain that is not tightly linked to specific movements. The aim of this study was to determine the effect of local and remote tonic cutaneous heat pain applied during training on motor learning of a finger-tapping sequence task. Forty-five healthy participants, randomized to the control, local pain or remote pain groups, were trained to perform an explicit finger motor sequence of five items as fast as possible. During the 10 training blocks (30 s each), local pain and remote pain groups received a heat pain stimulus on the wrist or leg, respectively. Performance was tested in the absence of pain in all groups before (baseline), immediately after (post-immediate), 60 min after (post-60 min) and 24 h after training (post-24 h) to assess both acquisition and next-day retention. Speed increased over time from baseline to post-24 h (p < 0.001), without any significant effect of group (p = 0.804) or time × group interaction (p = 0.385), indicating that the acquisition and retention were not affected by the presence of pain during training. No changes were observed on error rates, which were very low even at baseline. These results with experimental heat pain suggest that the ability to relearn finger sequence should not be affected by concomitant neuropathic pain in neurorehabilitation. However, these results need to be validated in the context of chronic pain, by including pain as a co-variable in motor rehabilitation trials.