Comprehensive Structural MRI Phenotyping in Oligophrenin 1-Related Disorder Reveals Characteristic Brain
Asthik Biswas1, Matthew T Whitehead2,3, Parthiv Haldipur4
1From the Department of Radiology (A.B., E.D.V., K.M., S.S.), Great Ormond Street Hospital for Children, National Health Service Foundation Trust, London, United Kingdom asthik.biswas@gosh.nhs.uk.
AJNR. American Journal of Neuroradiology
|July 1, 2026
Summary
Pathogenic variants in the Oligophrenin 1 (OPHN1) gene cause significant brain malformations. Detailed MRI reveals consistent cerebellar, brainstem, and supratentorial abnormalities, expanding the known OPHN1-related phenotype.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- The Oligophrenin 1 (OPHN1) gene encodes a Rho GTPase-activating protein regulating key cellular processes.
- OPHN1 variants are linked to structural brain malformations, with evolving neuroimaging descriptions.
- Previous studies noted nonspecific and specific brain abnormalities in OPHN1-related disorders.
Purpose of the Study:
- To systematically characterize the detailed MRI phenotype in patients with confirmed OPHN1 variants.
- To identify a consistent constellation of structural brain abnormalities associated with OPHN1 gene mutations.
Main Methods:
- Systematic, detailed MRI phenotyping was applied to patients with confirmed OPHN1 variants.
- Diffusion Tensor Imaging (DTI) was used to assess white matter tracts and axonal guidance.
- Comprehensive analysis of supratentorial, infratentorial, and brainstem structures was performed.
Main Results:
- A consistent pattern of abnormalities was identified, including cerebellar vermian/hemispheric hypoplasia with dysfoliation.
- Brainstem malformations included aberrant tracts like anterior mesencephalic cap dysplasia and abnormal transverse pontine fibers.
- Supratentorial findings comprised caudate hypoplasia, frontal ventriculomegaly, and commissural anomalies, alongside other developmental variations.
Conclusions:
- The study defines a characteristic MRI phenotype for OPHN1-related brain malformations.
- Findings suggest a pathogenic mechanism involving disrupted regional development, cerebrocerebellar connectivity, and axonal guidance.
- Detailed phenotyping expands the understanding of OPHN1-associated neurodevelopmental disorders.
