Abstract
<title>Abstract</title> <p> <bold>Background</bold> Pathogenic variants in <italic>FBXO11</italic> cause a syndromic neurodevelopmental disorder characterised by intellectual disability, behavioural abnormalities, and subtle facial dysmorphism. The genotypic-phenotypic spectrum remains incompletely defined. <bold>Methods</bold> We describe 21 previously unreported individuals with heterozygous pathogenic or likely pathogenic <italic>FBXO11</italic> variants identified through clinical exome/genome sequencing. Detailed phenotypic data were collected and compared with published cases. Facial similarity was assessed using GestaltMatcher. Based on aggregated data, we propose structured diagnostic criteria. <bold>Results</bold> Mild intellectual disability (86%), facial dysmorphism (67%), hypotonia (62%), and behavioural dysregulation (62%) were the most prevalent features. Microcephaly occurred in 24%, while seizures were present in 43%. Brain imaging abnormalities were nonspecific and did not consistently correlate with epilepsy. Variants included missense, truncating, and multi-exon deletions, supporting haploinsufficiency as the principal pathogenic mechanism. Computational facial analysis demonstrated measurable intra-cohort similarity. <bold>Conclusion</bold> <italic>FBXO11</italic> -related neurodevelopmental disorder frequently presents with mild cognitive impairment and subtle dysmorphism, suggesting under-recognition in milder cases. We propose semi-quantitative diagnostic criteria to support phenotypic assessment and variant interpretation. </p>