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.

Clinical Reasoning: A 40-Year-Old Woman Presenting With Encephalopathy and Paraparesis.

Patients with acute to subacute multifocal neurologic abnormalities often have a unique presentation, and their diagnosis and management can be challenging. We present the case of a 40-year-old patient who presented with a 4-day history of confusion, bradyphrenia, right facial droop, bilateral lower limb weakness, urinary incontinence, and hypothermia. This case highlights the diagnostic approach to patients with subacute multifocal neurologic abnormalities, the importance of considering coexisting systemic illnesses in the diagnosis, and their management. Readers will explore the diagnostic steps our group has considered to reach our final diagnosis and the importance of management for our leading diagnosis.