Untangling Neurodevelopmental Disorders in the Adulthood: A Movement Disorder is the Clue.

Abstract

BackgroundThe genetic landscape of neurodevelopmental disorders is constantly expanding and children with early-onset neurological phenotypes increasingly receive a genetic diagnosis. Nonetheless, the awareness of the chronic course of these conditions, and consequently their recognition and management in the adult population, is still limited. ResultsHerein, we describe four patients with rare neurodevelopmental disorders (SON, ZMYND11, DNMT1 and YY1-related diseases), who received a genetic allocation only in the adulthood. All these patients had an early developmental delay and displayed a movement disorder (dystonia/ataxia/tremor) which manifested for the first time, or worsened, in the adulthood, prompting the referral to a neurologist. The syndromic nature of the phenotype led eventually to the genetic testing. We report previously unrecognized features and highlight the peculiarities of the adult presentation of four neurodevelopmental disorders. ConclusionsThis report expands the current knowledge on four rare neurodevelopmental disorders (SON, ZMYND11, DNMT1 and YY1), which was mainly based on reports from paediatric cases. This case series emphasize the importance of a tight neurological surveillance extending beyond the childhood.

Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of autism associated geneZmynd11prior to onset of motor symptoms

“…Therefore, for the purpose of this study, 50-day old (pre-symptomatic) and 100-day old animals (post-symptomatic) were classified into respective groups, to represent stages of the disease. Among the aberrantly spliced genes, zinc finger, MYND typecontaining 11 ( Zmynd11 ) is of particular interest due to its recent implications in autism-related motor delay (Moskowitz, Belnap et al 2016); intellectual disability (Pruccoli, Graziano et al 2021) and brain atrophy and ataxia (Indelicato, Zech et al 2022). In addition, Zmynd11/ZMYND11 has been previously reported to be an RNA binding partner of TDP-43 in the mouse brain (Narayanan, Mangelsdorf et al 2013), rat cortical neurons (Sephton, Cenik et al 2010) and post-mortem human brain (Tollervey, Curk et al 2011) and was reported to be aberrantly spliced in the spinal cord of sporadic ALS patients with TDP-43 pathology (Rabin, Kim et al 2010).…”