Expanding clinical variability in FBXW7-related neurodevelopmental disorder: a multicenter case series.
Overview
14 affiliations
- Pediatric Clinic and Rare Diseases, Microcitemico Hospital “A. Cao”, University of Cagliari,Cagliari, Italy
- Department of Medical Sciences and Public Health, University of Cagliari,Cagliari, Italy
- Department of Medicine and Surgery, Saint Camillus International University of Health Sciences,Rome, Italy
- Department of Developmental Disabilities, IRCCS San Raffaele Roma,Rome, Italy
- Department of Biotechnological and Applied Clinical Sciences, Academic Unit of Pediatrics, University of L’Aquila,L’Aquila, Italy
- Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center,Omaha, NE USA
- Boystown National Research Hospital,Boystown, NE USA
- Department of Clinical and Experimental Medicine, University of Catania,Catania, 95131 Italy
- Institute of Neurology, Department of Health Sciences Centre for Research in Unusual Infections, Epilepsy and Neuroscience (CRUISE), Magna Graecia University,Catanzaro, 88100 Italy
- Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania “Luigi Vanvitelli”,Caserta, Italy
- Department of Clinical Genetics, Leiden University Medical Centre,Leiden, The Netherlands
- Department of Medicine and Surgery, University of Enna Kore,Enna, Italy
- European Brain Research Institute “Rita Levi-Montalcini” Viale Regina Elena,Rome, Italy
- Department of Pediatrics, University of Perugia,Perugia, Italy
Abstract
Background: Heterozygous variants in FBXW7 have recently been recognized as a cause of a rare neurodevelopmental disorder with variable developmental delay, neurological manifestations, and multisystem involvement. The breadth of clinical variability and penetrance remains incompletely defined.
Cases presentation: We report a retrospective multicenter case series of seven previously unreported individuals (five males, two females) with heterozygous FBXW7 variants identified through clinical genetic testing, aged 5–9 years at last evaluation (median 6 years). Six variants occurred de novo and one was inherited. Neurodevelopmental involvement was present in six individuals and was characterized by global developmental delay and language impairment; hypotonia was observed in all seven. Formal intellectual disability was documented in four cases, while one individual showed preserved cognitive functioning with predominant behavioral difficulties. Epileptic seizures occurred in four individuals, whereas three had no history of epilepsy. Brain MRI was available for six individuals and was normal in four, whereas two showed structural anomalies involving the corpus callosum. Extracerebral features were variably reported, most commonly constipation and recurrent respiratory/
Conclusions: This case series expands the phenotypic spectrum associated with FBXW7-related neurodevelopmental disorder and highlights variable expressivity and incomplete penetrance, including clinically relevant variants presenting with mild or atypical phenotypes. These findings support considering FBXW7 across a broad range of neurodevelopmental presentations and inform genetic counseling.
Supplementary Information: The online version contains supplementary material available at 10.1186/
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
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- figshare:32962714, at figshare; found in DataCite
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Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 6 keywords, 10 MeSH terms, 31 references.
Cite
This paper
Savasta, S., Comisi, F. F., Dell’Isola, G. B., Di Pasquale, G., Johnson, I., Herman, I., Comisi, A. M., Operto, F. F., Bargiacchi, G., Barge-Schaapveld, D. Q., Mangano, G. D., Carotenuto, M., Salpietro, V., & Verrotti, A. (2026). Expanding clinical variability in FBXW7-related neurodevelopmental disorder: a multicenter case series. Journal of neurodevelopmental disorders, 18(1), 42. https://
BibTeX
@article{savasta2026expa
author = {Savasta, Salvatore and Comisi, Francesco Fabrizio and Dell’Isola, Giovanni Battista and Di Pasquale, Gabriele and Johnson, Ivy and Herman, Isabella and Comisi, Andrea Maria and Operto, Francesca Felicia and Bargiacchi, Giuditta and Barge-Schaapveld, Daniëla Q.C.M. and Mangano, Giuseppe Donato and Carotenuto, Marco and Salpietro, Vincenzo and Verrotti, Alberto},
title = {{Expanding clinical variability in FBXW7-related neurodevelopmental disorder: a multicenter case series}},
journal = {Journal of neurodevelopmental disorders},
year = {2026},
month = jul,
volume = {18},
number = {1},
pages = {42},
publisher = {BMC},
issn = {1866-1947},
doi = {10.1186/
url = {https://
pmid = {42432493},
pmcid = {PMC13352821}
}
RIS
TY - JOUR
AU - Savasta, Salvatore
AU - Comisi, Francesco Fabrizio
AU - Dell’Isola, Giovanni Battista
AU - Di Pasquale, Gabriele
AU - Johnson, Ivy
AU - Herman, Isabella
AU - Comisi, Andrea Maria
AU - Operto, Francesca Felicia
AU - Bargiacchi, Giuditta
AU - Barge-Schaapveld, Daniëla Q.C.M.
AU - Mangano, Giuseppe Donato
AU - Carotenuto, Marco
AU - Salpietro, Vincenzo
AU - Verrotti, Alberto
TI - Expanding clinical variability in FBXW7-related neurodevelopmental disorder: a multicenter case series
T2 - Journal of neurodevelopmental disorders
J2 - J Neurodev Disord
PY - 2026
DA - 2026/
VL - 18
IS - 1
SP - 42
SN - 1866-1947
PB - BMC
DO - 10.1186/
UR - https://
LA - en
ER -
CSL-JSON
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