Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Radiography of scoliosis: Comparative dose levels and image quality between a dynamic flat-panel detector and a slot-scanning device (EOS system).

PURPOSE: To compare radiation dose and image quality between a slot-scanning system (SSS) and a dynamic flat-panel detector (DFD) in assessing scoliosis in children. METHODS: An experimental study was first performed with a phantom to assess the quality of each device. The clinical part included a prospective observational dosimetric and qualitative comparative study with acquisition of whole-spine X-ray: SSS (31 children), DFD (26 children). Institutional review board approval and informed consent were obtained. Dosimetric statistical analysis was performed from dose area product (DAP) and entrance skin dose measured by thermo-luminescent dosimeters localized in the cervical, thoracic and sacral areas. Assessment of the diagnostic quality (phantom and clinical) was realized by independent evaluation by 3 observers, using statistical analysis of quality score and inter-observer reproducibility. RESULTS: DAP was equivalent with the 2 systems. Entrance skin dose was significantly higher with DFD in thoracic and pelvic regions (P<0.05). Image quality scores of the SSS were significantly better than DFD for a majority of criteria, in both phantom and clinical evaluations. CONCLUSION: For scoliosis evaluation, the SSS, compared to the DFD system, offers enhanced image quality while reducing the entrance skin dose in the most radiosensitive areas.

[Neurological manifestations of an osteoid osteoma located on the femoral neck in an 8-year-old boy]. / Présentation neurologique d'un ostéome ostéoïde du col fémoral.

We report the case of an 8-year-old boy, suffering from nocturnal pain localized on the left groin and presenting as a limp over several months. Examination revealed diminished strength of the left leg, atrophy of the thigh and calf, and a diminished deep tendon reflex. The pain could be intense and the patient had found an analgesic position by pushing on his groin or by flexing his thigh on the pelvis. He could no longer run. He was unsuccessfully treated with carbamazepine and gabapentin. His evaluation included a negative abdominal ultrasound study and a normal spine and cerebral MRI. Electromyography was unremarkable. He finally underwent an MRI of the pelvis that revealed a hyperintense T2 signal of the left femoral neck; CT confirmed the diagnosis of osteoid osteoma. Radiofrequency ablation of the lesion was performed. His clinical state dramatically improved after the procedure. His walk is normal, without any limping. Deep tendon reflexes are normal, and he only presents residual pain. Physicians should be aware that osteoid osteoma may take the form of a slowly evolving neuropathy. We review the literature on this underestimated condition.