Określenie zaburzenia neurorozwojowego związanego z genem FBXO11: ocena kliniczna, molekularna i morfologiczna u 21 pacjentów
Defining FBXO11-Related Neurodevelopmental Disorder: Clinical, Molecular and Facial Assessment of 21 Patients
W skrócie
[Preprint - wstępne wyniki] Naukowcy przebadali 21 pacjentów z mutacjami genu FBXO11 powodującymi zaburzenia neurorozwojowe. U większości pacjentów stwierdzono łagodne problemy z rozwojem umysłowym (86%), subtelne cechy zmian twarzy (67%), osłabienie mięśni (62%) i problemy z zachowaniem (62%). Badacze zaproponowali kryteria diagnostyczne ułatwiające rozpoznanie tej rzadkiej choroby, która często bywa niedodiagnozowana w łagodniejszych przypadkach, a także padaczka występowała u 43% pacjentów.
Oryginalny abstract (angielski)
Abstract Background Pathogenic variants in FBXO11 cause a syndromic neurodevelopmental disorder characterised by intellectual disability, behavioural abnormalities, and subtle facial dysmorphism. The genotypic-phenotypic spectrum remains incompletely defined. Methods We describe 21 previously unreported individuals with heterozygous pathogenic or likely pathogenic FBXO11 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. Results 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. Conclusion FBXO11 -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.