Summary Gli proteins are transcriptional effectors of the Hedgehog (Hh) pathway in both normal development and cancer. We describe a program of multi-site phosphorylation that regulates the conversion of Gli proteins into transcriptional activators. In the absence of Hh ligands, Gli activity is restrained by the direct phosphorylation of six conserved serine residues by protein kinase a (PKA), a master negative regulator of the Hh pathway. Activation of signaling leads to a global remodeling of the Gli phosphorylation landscape: the PKA target sites become dephosphorylated, while a second cluster of sites undergoes phosphorylation. The pattern of Gli phosphorylation can regulate Gli transcriptional activity in a graded fashion, suggesting a phosphorylation based-mechanism for how a gradient of Hh signaling in a morphogenetic field can be converted into a gradient of transcriptional activity.

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Objectives-We hypothesized that: (1) fetal frontal horn (FH) morphology and their proximity to the cavum septi pellucidi (CSP) can assist in suspecting complete agenesis of the corpus callosum (cACC) and partial agenesis of the corpus callosum (pACC) earlier than known indirect ultrasound (US) findings; (2) FHs assist in differentiating a true CSP from a pseudocavum; and (3) magnetic resonance imaging (MRI) is useful in learning FH morphology and pseudocavum etiology. Methods-Thirty-two patients with cACC and 9 with pACC were identified on an Institutional Review Board-approved retrospective review. Of the 41 cases, 40 had prenatal US, and 21 had prenatal MRI; 17 had follow-up neonatal US, and 14 had follow-up neonatal MRI. Variables evaluated retrospectively were the presence of a CSP or a pseudocavum, ventricle size and shape, and FH shape (comma, trident, parallel, golf club, enlarged, or fused). Displacement between the inferior edge of the FH and the midline or cavum/pseudocavum was measured. Results-Fetal FHs had an abnormal shape in 77% ≤20 weeks' gestation, 86% ≤24 weeks, and 90% >24 weeks. Frontal horns were laterally displaced greater than 2 mm in 85% ≤20 weeks, 91% ≤24 weeks, and 95% >24 weeks. The CSP was absent in 100% of cACC cases and 78% of pACC cases, and a pseudocavum was present in 88% of cACC cases and 78% of pACC cases across gestation. Magnetic resonance imaging confirmed US pseudocavums to be focal interhemispheric fluid or an elevated/dilated third ventricle. Conclusions-Frontal horns assist in assessing ACC ≤24 weeks and throughout gestation. Pseudocavums, often simulating CSPs, are common in ACC. Frontal horn lateral displacement and abnormal morphology, recognized by MRI correlations, are helpful in differentiating a pseudocavum from a true CSP. A normal CSP should not be cleared on screening US unless normally shaped FHs are seen directly adjacent to it. Key Words-agenesis of the corpus callosum; cavum septi pellucidi; fetus; frontal horns; ventriculomegaly A genesis of the corpus callosum (ACC) is defined as complete or partial absence of the large commissure that connects the two cerebral hemispheres. Development

Rationale: Spontaneous anterior cervical or mediastinal hemorrhage is a rare presentation of parathyroid adenoma. Patient concerns: A 69-year-old woman presented with neck hematoma and dysphagia and was found to have a soft tissue mass adjacent to her thyroid gland as seen on MRI and neck ultrasound. Diagnosis: Laboratory testing demonstrated elevated calcium and parathyroid hormone supporting diagnosis of parathyroid adenoma. Interventions: She underwent right inferior parathyroidectomy and en bloc right hemithyroidectomy due to significant fibrosis. Outcomes: Pathology confirmed hypercellular parathyroid and normal thyroid tissue. Postoperatively, patient's calcium and parathyroid hormone levels had normalized. Lessons: In conclusion, imaging may not always be specific in identifying the source of neck hematoma and so laboratory studies should be done to rule out parathyroid adenoma as the underlying etiology.

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