1 - Serviço de Imagiologia, Unidade funcional de Neurorradiologia Diagnóstica, Centro Hospitalar de Vila Nova de Gaia/Espinho
2 - Serviço de Genética médica, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central
3 - Serviço de Neurorradiologia, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central
- XVIII congresso SPNR - 16 a 18 Novembro 2023, Braga
Introduction: Tubulinopathies comprise a wide and overlapping group of genetic diseases caused by pathogenic variants in genes encoding different isotypes of tubulin or microtubule-associated proteins that result in a variety of brain malformations. The recent evolution in genetic research and the knowledge of this kind of disorders has increased its awareness, enabling it’s earlier diagnosis.
Methods: Patients from two pediatric reference centers in Portugal were included. Genetically confirmed tubulinopathy patients were reviewed regarding the main clinical manifestations and genetic characteristics. Neuroradiological features associated with tubulinopathies will be described, including the current background on genetic-phenotypic correlations as well as a pictorial review with emphasis on common patterns that may raise the suspicion of tubulinopathies.
Results: The clinical features of the tubulinopathies include non-specific motor and intellectual disabilities. Individuals with milder clinical expression survive into adulthood, while those with more severe disease may die at a young age. As there is no pathognomonic clinical feature associated with tubulinopathies, imaging studies and respective neuroradiological findings play a crucial role in the diagnosis. Tubulinopathies imaging manifestations include a spectrum of cortical developmental malformations (CDM), commissural anomalies; hypoplasia of the internal capsules, mostly the anterior limbs [absent anterior limb of the internal capsule (ALIC) sign], anomalies of the deep gray nuclei; hippocampal anomalies; hypoplasia of the brainstem, cerebellar hemispheres, and vermis; and corticospinal tracts and cranial nerves hypoplasia.
Conclusions: Tubulinopathies are heterogeneously presenting genetic diseases, with a wide spectrum of clinical and imaging manifestations, with many genes involved in it’s pathophysiology. This review of genetically-proven tubulinopathy patients demonstrates the relevance of a systematic imaging approach of brain MRI evaluation, in such a way that its knowledge and recognition can constitute the first step in suggesting the diagnosis of this complex group of pathologies.
Keywords: Tubulinopathies; brain; MRI