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Joubert syndrome (JS) is an inherited neurodevelopmental ciliopathy with wide clinical and genetic heterogeneity, whose paradigmatic sign is a peculiar cerebellar and brainstem malformation known as the ‘molar tooth sign’. Recessive pathogenic variants in the HYLS1gene are associated with hydrolethalus syndrome (HLS), a severe disorder characterised by multiple developmental defects leading to intrauterine or perinatal death. However, HYLS1biallelic variants were also reported in three individuals with JS.Here, we report a fourth patient with a purely neurological JS carrying two compound heterozygous missense variants in the HYLS1gene. Notably, while all patients with lethal HLS had both variants falling within the highly conserved HYLS-1 Box, the four patients with milder JS phenotype featured at least one variant external to this evolutionary conserved domain, suggesting a possible correlation between the mutation site and the severity of the phenotype.

The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration, following disruption of the neuroependyma and impaired neuronal motility. Growing evidence indicates that the FLNA-dependent actin dynamics and regulation of vesicle formation and trafficking by activation of ADP-ribosylation factors (ARFs) can play an important role in this cortical malformation. We report the first inherited variant of ARF1in a girl with intellectual disability and periventricular nodular heterotopia who inherited the variant from the father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, both patients presented some features suggestive of hypohidrotic ectodermal dysplasia. These clinical features showed similarities to those of three previously reported cases with ARF1missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.

Introduction: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials. This national initiative, here presented, aims to address the following knowledge gap: a) how much does histological diversity translate into clinical manifestation variety? b) are those chemotherapy regimens, recommended for conventional biliary tract cancers, potentially active in rare variants? Therefore, epidemiological, pathological, and clinical characterization of series of rare biliary histotypes/variants, for which therapeutic and follow-up data are available, will be collected.Methods: An Italian task force on rare tumors of the biliary tract (IRaBiCa) has been created, whose initiative is a multicenter retrospective study involving 34 Italian cancer centers. Clinical data from approximately 100 patients will be collected and analyzed. Continuous variables will be presented as median ± standard deviation, while categorical variables will be expressed in terms of frequency. Kaplan-Maier analyses will be used to compare disease free, progression free and overall survival, according to the different histotypes.Conclusions: We expect to gather novel data on rare histotypes of biliary tract cancer that will be useful to support their molecular and immunological characterization.

Common postictal MRI findings include transient cortical T2 hyperintensity, restricted diffusion, and gyral and/or adjacent leptomeningeal contrast enhancement. In certain uncommon pathological conditions, other signal abnormalities can be present, suggesting a different underlying pathogenic mechanism. We report the case of a 66‐year‐old man, recently diagnosed with diabetes mellitus type 2, presenting with new‐onset visual and auditory hallucinations, “absence” seizures, and repeated peaks of hyperglycaemia without hyperketonaemia or increased serum osmolarity. EEG confirmed epileptic discharges in the right temporal region and MRI showed vast subcortical T2 hypointensity in the right temporal lobe, without any cortical hyperintensity, restricted diffusion, or contrast enhancement. Subcortical signal abnormality and EEG discharges resolved after a month of follow‐up, with a small juxtacortical gliotic focus as a sequela. Peaks in hyperglycaemia have been reported to be responsible for T2 hypointense subcortical abnormalities through a proconvulsant mechanism linked to increased ketone body concentrations. Hyperosmolarity and hyperketonaemia were not evident in this case, however, transient accumulation of free radicals that alter the intercellular space can be considered the presumable cause of this finding. In summary, it is important to consider any unusual findings on postictal MRI in order to avoid errors in interpretation.

Meningioma is a common primary brain tumor in adults. The treatment approach depends on its grade, size and symptoms. The case reported here was a repeatedly recurring transitional meningioma, previously treated with several surgical procedures and two sessions of cranial radiosurgery. At the time of last relapse, temozolomide was administered alone and combined with external beam radiation therapy. At the last follow-up after 38 months, the disease was stable. In conclusion, in this case of plurirecurrent meningioma, treatment with temozolomide alone and in combination with radiotherapy was feasible and associated with limited morbidity, providing clinical benefit and long local disease control. We discuss the case comparing our approach with other experiences reported in the literature.

The ventriculus terminalis is an ependymal cystic cavity in the conus medullaris, sometimes found in children. Persistence of the ventriculus terminalis in adults can cause lower back pain or neurological disturbances. However, there are no literature reports of de novo formation of a ventriculus terminalis in the conus medulallaris, as in the case we illustrate here.

Computed tomography of dermoids and epidermoids usually demonstrates areas of variable hypodensity, located most frequently in the sellar region and in the cerebellopontine angle. This report presents two cases of hyperdense dermoids of the craniocervical region which are compared with six other cases described in the literature.

We report on a patient with a multiple congenital abnormalities/mental retardation (MCA/MR) syndrome including facial abnormalities, agenesis of the corpus callosum, heart defect, 1st ray anomalies of the upper limb, and ambiguous genitalia, whose phenotype overlaps a previous description of XK syndrome. The patient has a ring chromosome (13) with deletion 13q32-qter. Molecular analysis demonstrated loss of the region from D13S317 to D13S285 and a paternal origin of the anomaly. Am. J. Med. Genet. 72:319–323, 1997. © 1997 Wiley-Liss, Inc.

The brain CT findings in 54 patients in coma 1–5 (Bozza-Marrubini scale) following craniocerebral trauma are analysed retrospectively. Attention is focused on those of the CT features that constitute indirect signs of brainstem involvement: obliteration of the suprasellar cisterns, distortion of the perimesencephalic and quadrigeminal cisterns, dilatation of the temporal horn and widening of the cerebellopontine angle cistern on the lesion side, considered anatomically and clinically responsible for coma. The patients fell into three groups: 7 with negative CT, 31 with intracranial lesions not affecting the brainstem and 16 with CT evidence of descending transtentorial herniation. The CT signs correlated significantly with coma level and survival. These CT signs can be used alongside the clinical and other instrumental data — EEG, VEP and intracranial pressure — as a further criterion of severity in headinjury coma.