ATR-X Syndrome

The mutational status of alpha-thalassemia X-linked intellectual disability (ATRX) is an important indicator for the treatment and prognosis of high-grade gliomas, but reliable ATRX testing currently requires invasive procedures. The objective of this study was to develop a clinical trait-imaging fusion model that combines preoperative magnetic resonance imaging (MRI) radiomics and deep learning (DL) features with clinical variables to predict ATRX status in isocitrate dehydrogenase (IDH)-mutant high-grade astrocytoma.

A total of 234 patients with IDH-mutant high-grade astrocytoma (120 ATRX mutant type, 114 ATRX wild type) from 3 centers were retrospectively analyzed. Radiomics and DL features from different regions (edema, tumor, and the overall lesion) were extracted to construct multiple imaging models by combining different features in different regions for predicting ATRX status. An optimal imaging model was then selected, and its features and linear coefficients were used to calculate an imaging score. Finally, a fusion model was developed by combining the imaging score and clinical variables. The performance and application value of the fusion model were evaluated through the comparison of receiver operating characteristic curves, the construction of a nomogram, calibration curves, decision curves, and clinical application curves.

The overall hybrid model constructed with radiomics and DL features from the overall lesion was identified as the optimal imaging model. The fusion model showed the best prediction performance with an area under curve of 0.969 in the training set, 0.956 in the validation set, and 0.949 in the test set as compared to the optimal imaging model (0.966, 0.916, and 0.936, respectively) and clinical model (0.677, 0.641, 0.772, respectively).

The clinical trait-imaging fusion model based on preoperative MRI could effectively predict the ATRX mutation status of individuals with IDH-mutant high-grade astrocytoma and has the potential to help patients through the development of a more effective treatment strategy before treatment.

To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome.

An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS).

The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother.

The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.

To investigate whether T2-weighted imaging-fluid-attenuated inversion recovery (T2/FLAIR) mismatch, T2∗ dynamic susceptibility contrast (DSC) perfusion, and magnetic resonance spectroscopy (MRS) correlated with the histological diagnosis and grading of IDH (isocitrate dehydrogenase)-mutant, 1p/19q non-co-deleted/ATRX (alpha-thalassemia mental retardation X-linked)-mutant astrocytoma.

Imaging of 101 IDH-mutant diffuse glioma cases of histological grades 2-3 (2019-2021) were analysed retrospectively by two neuroradiologists blinded to the molecular diagnosis. T2/FLAIR mismatch sign is used for radio-phenotyping, and pre-biopsy multiparametric MRI images were assessed for grading purposes. Cut-off values pre-determined for radiologically high-grade lesions were relative cerebral blood volume (rCBV) ≥2, choline/creatine ratio (Cho/Cr) ≥1.5 (30 ms echo time [TE]), Cho/Cr ≥1.8 (135 ms TE).

Sixteen of the 101 cases showed T2/FLAIR mismatch, all of which were histogenetically confirmed IDH-mutant 1p/19q non-co-deleted/ATRX mutant astrocytomas; 50% were grade 3 (8/16) and 50% grade 2 (8/16). None showed contrast enhancement. Nine of the 16 had adequate multiparametric MRI for analysis. Any positive value by combining rCBV ≥2 with Cho/Cr ≥1.5 (30 ms TE) or Cho/Cr ≥1.8 (135 ms TE) predicted grade 3 histology with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%.

The T2/FLAIR mismatch sign detected diffuse astrocytomas with 100% specificity. When combined with high Cho/Cr and raised rCBV, this predicted histological grading with high accuracy. The future direction for imaging should explore a similar integrated layered approach of 2021 classification of central nervous system (CNS) tumours combining radio-phenotyping and grading from structural and multiparametric imaging.