AUSTIN, TX — The FBXO31 Foundation today announced the publication of a landmark study in Clinical Genetics that formally names a rare genetic neurodevelopmental disorder “Kruer syndrome.” The paper, titled “Expanding the Phenotypic Spectrum of the Recurrent De Novo FBXO31 p.Asp334Asn Variant: Evidence for a Novel Neurodevelopmental Disorder (Kruer Syndrome),” describes the largest cohort of patients with this specific FBXO31 variant to date and establishes a clear, recognizable clinical picture that can guide diagnosis worldwide.
Published in Clinical Genetics (DOI: 10.1111/cge.70166), the study was led by researchers at the University of Arizona College of Medicine – Phoenix, Phoenix Children’s Hospital, and an international team spanning institutions in the United States, France, Slovakia, and Germany.
A Name for a Condition That Was Once Invisible
For many families, a child’s journey with FBXO31-related disease has been marked by years of diagnostic uncertainty. Cerebral palsy, intellectual disability, speech impairment, and challenging behaviors—often without a clear genetic explanation. This study changes that.
“This study establishes Kruer syndrome as a recognizable and diagnosable condition. Our goal now is to ensure that no child with this variant goes unidentified, and to build the evidence base that will eventually lead to treatments” reports Michael C. Kruer, MD, University of Arizona College of Medicine.
The research team studied seven individuals, all of whom carry the same spontaneous (de novo) genetic change in FBXO31: the variant c.1000G>A (p.Asp334Asn). By combining detailed neurological, behavioral, and physical assessments with brain imaging and facial analysis, the team identified a consistent, recognizable syndrome:
- Cerebral palsy with a mix of low muscle tone (hypotonia), increased muscle stiffness (spasticity), and involuntary movements (dystonia)
- Global developmental delay and intellectual disability in all seven individuals
- Speech and language impairment in all seven individuals
- Neuropsychiatric features including ADHD, anxiety, stereotypies, autistic features, and behavioral dysregulation in some patients
- Characteristic brain MRI findings, most notably a smaller-than-typical corpus callosum (hypoplastic corpus callosum), seen in four of seven patients
- A subtle but consistent facial appearance recognizable across all probands, including a prominent forehead, sparse eyebrows, periorbital fullness, thin upper lip, and retrognathia
The eponym “Kruer syndrome” honors Dr. Michael C. Kruer, the neurologist-scientist whose laboratory identified the first cases and provided the foundational laboratory evidence that the p.Asp334Asn variant disrupts normal FBXO31 protein function. The name was proposed with the full support of the FBXO31 Foundation patient advocacy community.
What This Means for Families
One of the most significant barriers for families affected by FBXO31-related disorders has been the absence of the gene from standard clinical genetic testing panels for cerebral palsy and neurodevelopmental disorders. As a result, many individuals may remain undiagnosed for years—or never receive a diagnosis at all. For the families in our community, identifying symptoms and having a name for this condition is profound. It means our children are seen, our experiences are validated, and it confirms that the scientific community is working toward answers. This gives us renewed hope” explains Laura Scott Avery, Founder and Chair of the FBXO31 Foundation.
The study authors are calling on clinicians and genetic testing laboratories to include FBXO31 in diagnostic panels for cerebral palsy and neurodevelopmental disorders. A diagnosis matters: it ends the diagnostic odyssey, connects families with one another and with appropriate resources, informs medical management, and opens the door to future therapies.
The research team also highlights that the biology of this mutation—a “neomorphic” gain of abnormal function rather than simple gene loss—makes it a strong candidate for emerging gene-silencing therapies such as antisense oligonucleotides (ASOs), a treatment approach that has shown promise in other genetic neurological conditions.
On behalf of the FBXO31 Foundation, Executive Director Mary Beth Kiser expressed
“deepest gratitude to Drs. Michael Kruer and Carolina Galaz Montoya, whose tireless dedication, scientific rigor, and unwavering advocacy have transformed the lives of affected families. Their commitment to uncovering answers and advancing this research brings us closer, every day, to the treatments and ultimately the cure that our community deserves.”
About the Study
The study was authored by researchers at the University of Arizona College of Medicine – Phoenix, Banner University Medical Center, Phoenix Children’s, Advocate Children’s Hospital, La Pitié-Salpêtrière Hospital (Paris), Hôpital Trousseau (Paris), University Hospital of L. Pasteur (Košice, Slovakia), Technical University of Munich, GeneDx, Children’s Hospital of Philadelphia, and Boston Children’s Hospital. Funding was provided by the Cerebral Palsy Alliance Research Foundation, NIH grants R01 NS106298 and R01 NS127108, and other international sources.
About the FBXO31 Foundation
The FBXO31 Foundation is a patient advocacy organization dedicated to supporting families affected by FBXO31-related genetic disorders. The Foundation works to accelerate research, improve diagnosis, connect families, and drive the development of treatments. To learn more or get involved, visit www.fbxo31foundation.org.
Media Contact
Mary Beth Kiser, Executive Director
FBXO31 Foundation
mbkiser@fbxo31foundation.org