Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome

KBG syndrome (OMIM 148050) is a very rare genetic disorder characterized by macrodontia, distinctive craniofacial abnormalities, short stature, intellectual disability, skeletal, and neurologic involvement. Approximately 60 patients have been reported since it was first described in 1975. Recently mutations in ANKRD11 have been documented in patients with KBG syndrome, and it has been proposed that haploinsufficiency of ANKRD11 is the cause of this syndrome. In addition, copy number variation in the 16q24.3 region that includes ANKRD11 results in a variable phenotype that overlaps with KBG syndrome and also includes autism spectrum disorders and other dysmorphic facial features. In this report we present a 2½‐year‐old African American male with features highly suggestive of KBG syndrome. Genomic microarray identified an intragenic 154 kb deletion at 16q24.3 within ANKRD11. This child's mother was mosaic for the same deletion (present in approximately 38% of cells) and exhibited a milder phenotype including macrodontia, short stature and brachydactyly. This family provides additional evidence that ANKRD11 causes KBG syndrome, and the mild phenotype in the mosaic form suggests that KBG phenotypes might be dose dependent, differentiating it from the more variable 16q24.3 microdeletion syndrome. This family has additional features that might expand the phenotype of KBG syndrome. © 2013 Wiley Periodicals, Inc.     

Retrospective analysis of survival outcomes and the role of cisplatin-based chemotherapy in patients with urethral carcinomas referred to medical oncologists

ObjectivesPrimary carcinomas of the urethra (PCU) are rare and often advanced when diagnosed. Treatment standards are lacking. We studied treatment response and survival in a cohort of patients with PCU, with emphasis on modern platinum-containing chemotherapy regimens plus surgery for advanced disease.Materials and methodsThis was a retrospective chart review of consecutive patients with PCU seen by medical oncologists at our institution over a recent 5-year period. Outcome was measured as best response to chemotherapy. Kaplan-Meier estimates were generated for survival and Cox proportional hazard was used for prognostic factors for survival.ResultsThe 44 patients (64% women) included had a median age at diagnosis of 66.5 years. The most prevalent histologic subtypes of PCU were squamous cell carcinoma and adenocarcinoma. At diagnosis, 43% already had lymph node-positive [lymph node (LN)+] disease, and 16% had distant metastases. The entire cohort's overall survival (OS) was 31.7 months. The response rate to platinum-containing neoadjuvant chemotherapy was 72%. Twenty-one patients with locally advanced or LN+ PCU underwent chemotherapy plus surgery. Their median OS from chemotherapy initiation was 25.6 months. Four of 9 patients (44%) with LN+ PCU at diagnosis were alive at our review, with a minimum follow-up of more than 3 years.ConclusionsModern platinum-containing regimens appear to be effective in advanced PCU. Preoperative chemotherapy is associated with prolonged disease-free survival in a subgroup of LN+ cases.     

The Utility and Financial Implications of Obtaining Routine Lead Levels for Child Psychiatric Inpatients

This study attempted to challenge the CDC recommendations regarding routine screening blood lead levels in children. The purpose was to determine the efficacy of obtaining routine lead levels on all patients admitted to a child psychiatric inpatient unit. A retrospective chart review of children admitted to a psychiatric inpatient unit during a 12 month period. The audit determined average lead levels and costs associated with the screening program. 1 of 61 admitted children was found to have an elevated lead level. Number needed to treat was determined to be 98. The cost per case detected was determined to be over $8,600. Routine screening for blood lead levels in all children admitted to a psychiatric inpatient unit does not appear efficacious or cost effective.     

Acculturation and a Potential Relationship with Oral Health Outcomes Among Somali Refugees in Massachusetts

This paper explores the relationship between acculturation and oral health in a study of Somali refugees. This cross-sectional survey included structured surveys and dental examinations of a convenience sample of 439 Somali adults living in Massachusetts. Associations between an acculturation scale and: (1) lifetime history of caries and (2) access to oral health services were calculated. In bivariate analyses, many individual questions in the scale were associated with outcomes. In multivariate analysis, speaking English (OR 0.5, CI 0.28–0.84) was associated with better access to, and utilization of, dental health services while reading American books and newspapers in English was associated with increased lifetime history of dental disease (OR 2.6, CI?1.1–6.0). As specific elements of acculturation have different relationships with oral health among Somali refugees, a summary acculturation scale may have limited utility. Ongoing efforts to remove language barriers may improve oral health.