Monitoring and addressing anticholinergic-induced ocular adverse effects associated with psychotropic medication.

Pathogenic heterozygous variants in are responsible for Snijders Blok–Fisher syndrome (SNIBFIS; OMIM #618604), a rare autosomal dominant neurodevelopmental disorder (NDD) characterized by developmental delay (DD), variable degrees of intellectual disability (ID), speech and language impairment, dysmorphic features, hypotonia, as well as behavioral and psychiatric comorbidities. The core clinical features associated with this recently recognized disorder were initially delineated through the description of a cohort of 19 individuals harboring heterozygous disruptions (). Recently, larger phenotypic datasets have been reported recruiting novel patients with variants through international collaborative efforts, enabling further refinement of the associated clinical spectrum. Additional manifestations described include ophthalmological abnormalities, hearing loss, sleep disturbances, gastrointestinal comorbidities, joint hypermobility, and epilepsy, the latter representing a less common but clinically relevant feature with an expanding phenotypic spectrum (). gene is located at cytoband 2q12.1 and contains two functional domains, POU-Specific (POU-S) and POU-Homeodomain (POU-H), which are essential for the site-specific binding to the different target genes. Since is an intronless gene, transcripts harboring premature termination codons are expected to be relatively insensitive to nonsense-mediated mRNA decay (NMD) (), potentially resulting in the expression of truncated proteins. Functional studies based on luciferase assays demonstrated both loss and gain of function mechanisms underlying the molecular basis of this disorder (). Recent genotype–phenotype studies have been proposed. Loss-of-function variants have been reported to be enriched among individuals presenting with dysmorphic features and sensory abnormalities, whereas epilepsy has been more frequently associated with gain-of-function variants affecting the POU-S or POU-H domains. Notably, no significant differences in the overall severity of DD or ID have been observed between truncating and non-truncating variants (). To date, approximately 30 families have been reported, with the majority of cases resulting from variants (; ). To our knowledge, only two truncating variants, p. (Ser24Ter) () and p. (Arg451Leufs*185) () have been reported as inherited form an affected parent, and no instances of germline mosaicism have been described. Here, we report, for the first time, two affected siblings harboring a truncating variant inherited from their apparently unaffected father.