Non-syndromic Sensorineural Prelingual Deafness: The Importance of Genetic Counseling in Demystifying Parents’ Beliefs About the Cause of Their Children’s Deafness

Recent advances in molecular genetics have allowed the determination of the genetic cause of some childhood non-syndromic deafness. In Portugal only a small proportion of families are referred to a clinical genetics service in order to clarify the etiology of the deafness and to provide genetic counseling. Consequently, there are no published studies of the prior beliefs of parents about the causes of hereditary deafness of their children and their genetic knowledge after receipt of genetic counseling. In order to evaluate the impact of genetic counseling, 44 parents of 24 children with the diagnosis of non-syndromic sensorineural prelingual deafness due to mutations in the GJB2 (connexin 26), completed surveys before and after genetic counseling. Before counseling 13.6 % of the parents knew the cause of deafness; at a post-counseling setting this percentage was significantly higher, with 84.1 % of the parents accurately identifying the etiology. No significant differences were found between the answers of mothers and fathers either before or after genetic counseling. Parents' level of education was a significant factor in pre-test knowledge. After genetic counseling 95.5 % of the parents stated that the consultation had met their expectations, 70.5 % remembered correctly the inheritance pattern, and 93.2 % correctly recalled the chance of risk of deafness. These results underline the importance of genetic counseling in demystifying parents' beliefs about the etiology of their children's deafness

Use of Panitumumab-IRDye800 to Image Microscopic Head and Neck Cancer in an Orthotopic Surgical Model

BACKGROUND: Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. METHODS: A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting EGFR (panitumumab) or non-specific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96hrs following systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. RESULTS: Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9(Pearl) and 2.3(SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P<0.05). Tissue biopsies (average size=3.7mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n=25/25). Biopsies of non-fluorescent tissue were proven to be negative for malignancy (n=28/28). The SPY was able to detect regional lymph node metastasis (<1.0mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey. CONCLUSIONS: Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology