Case Report: Inactivating PTH/PTHrP Signaling Disorder Type 1 Presenting With PTH Resistance.

PTH resistance is characterized by elevated parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia and it is classically associated with GNAS locus genetic or epigenetic defects. Inactivating PTH/PTHrP signaling disorders (iPPSD) define overlapping phenotypes based on their molecular etiology. iPPSD1 is associated with PTH1R variants and variable phenotypes including ossification anomalies and primary failure of tooth eruption but no endocrine disorder. Here we report on a 10-month-old child born from consanguineous parents, who presented with mild neurodevelopmental delay, seizures, enlarged fontanelles, round face, and bilateral clinodactyly. Hand x-rays showed diffuse delayed bone age, osteopenia, short metacarpal bones and cone-shaped distal phalanges. A diagnosis of PTH resistance was made on the basis of severe hypocalcemia, hyperphosphatemia, elevated PTH and normal vitamin D levels on blood sample. The patient was treated with calcium carbonate and alfacalcidol leading to rapid bio-clinical improvement. Follow-up revealed multiple agenesis of primary teeth and delayed teeth eruption, as well as Arnold-Chiari type 1 malformation requiring a ventriculoperitoneal shunt placement. GNAS gene analysis showed no pathogenic variation, but a likely pathogenic homozygous substitution c.723C>G p.(Asp241Glu) in PTH1R gene was found by trio-based whole exome sequencing. We studied the deleterious impact of the variant on the protein conformation with bioinformatics tools. In conclusion, our study reports for the first time PTH resistance in a child with a biallelic PTH1R mutation, extending thereby the clinical spectrum of iPPSD1 phenotypes.

Development of Vitreoretinal Lymphoma in a Patient with Sarcoid Uveitis.

PURPOSE: The purpose of this article is to report the first case of primary vitreoretinal lymphoma in a patient with sarcoid uveitis. MATERIAL AND METHODS: A 63-year-old woman with biopsy-proven sarcoid uveitis diagnosed 7 years ago was presented for a 6-month history of bilateral intermediate uveitis and gait disturbance with cerebral magnetic resonance imaging suggestive of neurosarcoidosis. Because of corticoids resistance, a vitrectomy and a cerebral biopsy were performed. The final diagnosis was primary central nervous system diffuse lymphoma. Patient died despite the chemotherapy with an initial improvement of visual and neurological features. CONCLUSION: Ophthalmologists should know that patient followed up with sarcoid uveitis can develop a primary vitreoretinal diffuse large B-cell lymphoma.

Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: comparison with clinical and radiologic examinations.

BACKGROUND: Neck metastasis is a major prognostic factor of head and neck carcinoma, but its preoperative detection is currently unreliable. Molecular markers of the metastatic potential of a carcinoma would help to avoid unnecessary neck dissection in patients with nonmetastatic cancer. METHODS: The fractions of cancer cells immunostained for proliferating cell nuclear antigen (PCNA) and Ki67 were determined in 80 preoperative biopsy specimens of head and neck carcinomas. The value of both indexes to detect metastasis in the subsequent neck dissection was compared with that of the clinical and radiologic examinations. RESULTS: PCNA and Ki67 indexes correlated with neck metastasis. Cutoff points were determined for both indexes to discriminate metastatic from nonmetastatic carcinomas. By multivariate logistic regression, these indexes were significant predictors of metastases, together with clinical T stage and neck palpation. CONCLUSION: The fraction of cancer cells immunolabeled for PCNA or Ki67 in preoperative biopsy specimens is helpful to predict neck metastasis.