Expanding the Phenotypic Spectrum of the Recurrent De Novo FBXO31 p.Asp334Asn Variant: Evidence for a Novel Neurodevelopmental Disorder Proposed as Kruer Syndrome

This peer-reviewed study expands recognition of a distinct, autosomal-dominant neurodevelopmental disorder caused by a recurrent de novo FBXO31 p.Asp334Asn variant. Through re-evaluation of previously reported cases and identification of additional individuals, the authors define a recognizable clinical phenotype that includes mixed-tone cerebral palsy, global developmental delay/intellectual disability, speech impairment and prominent neuropsychiatric features (e.g., ADHD, anxiety, autistic features). Neuroimaging commonly demonstrates hypoplastic corpus callosum and posterior-predominant white-matter abnormalities. 

Michael Kruer, MD, et al., pediatric neurologist and physician-scientist at Phoenix Children’s, is senior author of this research alongside co-authors from multiple institutions. Together with the validating laboratory and the FBXO31 Foundation, the authors propose the eponym ‘Kruer syndrome’ for this newly characterized neurodevelopmental disorder, in recognition of Dr. Kruer’s foundational contributions to the field.

Clinical Impact

The authors recommend including FBXO31 in diagnostic algorithms for cerebral palsy and neurodevelopmental disorders, reinforcing the value of genetic evaluation for diagnostic precision, counseling and care planning. Read the Study

Phoenix Children's Pediatric Movement Disorders Program accepts referrals for children with cerebral palsy, neurodevelopmental disorders, and suspected genetic movement conditions. To refer a patient or request a consultation, call 602-933-KIDS (5437) or submit a referral online.

REFERENCE

Galaz-Montoya CI, et al. Expanding the Phenotypic Spectrum of the Recurrent De Novo FBXO31 p.Asp334Asn Variant: Evidence for a Novel Neurodevelopmental Disorder (Kruer Syndrome). Clin Genet. 2026. doi:10.1111/cge.70166. PubMed ID 41858232.