Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

Refractory bleeding from a giant de-differentiated liposarcoma of the chest wall: An indication for neoadjuvant chemotherapy and palliative resection? - A case report.

INTRODUCTION: Dedifferentiated liposarcoma (DDLPS) is a heterogenous neoplasm of variable histological grade. DDLPS uncommonly arises from the chest wall. There are limited data available about the tumor's response to chemotherapy and accessible reports indicate minimal benefits. Surgery is thus the cornerstone of management. Here, we demonstrate an uncommon situation where chemotherapy was used to arrest bleeding from a giant DDLPS that was refractory to all available hemostatic agents. This case also presents an uncommon indication for palliative chest wall resection and reconstruction (CWRR). PRESENTATION OF CASE: A 55-year old woman presented with refractory bleeding from an ulcerated and foul-smelling mass on the anterior chest wall, confirmed histologically to be DDLPS. Chemotherapy with Doxorubicin and Ifosfamide was used to control the bleeding. She subsequently had CWRR to improve her quality of life. The patient made an uneventful recovery but later died from pulmonary embolism. DISCUSSION: The dedifferentiated component of DDLPS is vascular and may account for why we were able to exhibit a hemostatic response to chemotherapy. CWRR was then employed to improve the quality of life in an advanced, ulcerated and infected tumor of the chest wall. CONCLUSION: We were able to demonstrate a hemostatic response of DDLPS to neoadjuvant chemotherapy and anticipate that this report may serve as a reference for further studies. Furthermore, we believe that palliative resection may be carried out to improve a patient's quality of life even in the face of advanced disease.

Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts.

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits. METHODS: We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. RESULTS: We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome. CONCLUSION: Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.

Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

OBJECTIVE: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. PATIENTS AND METHOD: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. RESULTS: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. CONCLUSION: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

Malignant skin lesions in Oshogbo, Nigeria.

INTRODUCTION: The aim of this study is to retrospectively assess the prevalence of some of skin malignancies in our environment and to provide a data base for creating awareness for prevention and early detection of the diseases in order to reduce morbidity and mortality associated with these skin lesions in our environment. METHODS: This is a retrospective study of all histologically diagnosed malignant skin lesions which presented at Ladoke Akintola University of Technology Teaching Hospital Osogbo Osun State between January 2006 and December 2010. RESULTS: Ninety- eight patients presented with skin cancers out of which 60 (61.2%)were males and 38 (38.8%) were females. Malignant melanoma ranked highest followed by squamous cell carcinoma, dermatofibrosarcoma and basal cell carcinoma in that order. Malignant melanoma affects male more than female and it commonly affects lower limbs. CONCLUSION: Skin malignancies pose a burden to the economy of the country. Efforts should be directed toward prevention, early diagnosis and management in order to abolish or reduce morbidity, as well as mortality associated with late presentation of people in the developing countries.

Awareness and attitude of healthcare workers to cosmetic surgery in osogbo, Nigeria.

This study aimed at understanding the level of awareness and elucidates the attitude and disposition of healthcare workers to cosmetic surgery in Osogbo, Nigeria. A questionnaire-based survey was done at LAUTECH Teaching Hospital, Osogbo, in 2012. Questionnaires were administered to 213 workers and students in the hospital. These were then analysed using SPSS version 16.0 with frequencies, means, and so forth. Respondents were 33 doctors, 32 nurses, 79 medical students, 60 nursing students, 4 administrative staff, 1 pharmacist, and 4 ward maids. There is fair awareness about cosmetic surgery generally with 94.5% and its availability in Nigeria with 67.0%. A fewer proportion of the respondents (44.5%) were aware of the facility for cosmetic surgery in their locality. A large percentage (86.5%) favorably considers facilities outside Nigeria when making choice of facility to have cosmetic surgery done. 85.5% considered the information about cosmetic surgery reliable while 19.0% objected going for cosmetic surgery of their choice even if done free. Only 34.0% consider cosmetic surgery socially acceptable. Although the awareness of health workers about cosmetic surgery is high, their disposition to it is low. There is a need to increase the awareness in order to increase cosmetic surgery practice in Nigeria.

Knowledge, attitude and practice of prophylactic mastectomy among patients and relations attending a surgical outpatient clinic.

INTRODUCTION: Prophylactic mastectomy (PM) is uncommon in our practice. This study documents the knowledge and attitude of patients and relation to prophylactic mastectomy. METHODS: Adults attending surgical outpatient unit were interviewed. Biodata, awareness of breast cancer, and attitude towards prophylactic mastectomy were inquired about and documented. RESULTS: Two hundred and forty eight (99 men and 149 women) were involved. Most, 75.6%, were age bracket 20-29 years and 77.2% had tertiary education. Only 26 (10.4%) of the respondents had previous history of breast diseases. 96.4% were aware of cancer of the breast while 113 (45.2%) of them were aware that breast cancer gene can be inherited from parents and 60 (24.2%) believe cancer of the breast can affect women with strong positive family history. Only 64 (25.6%) of them would agree to prophylactic mastectomy if found necessary. Reasons given for possible refusal to consent to PM include effect on beauty, (40%), psychological effect, (22.8%), non-curing of disease, (18%), possible surgical complications, (7.2%), and financial cost, (1.2%). Presence of unilateral breast cancer and high risk status constituted about 71% of suggested possible indications for PM while presence of any breast disease was suggested by only 7.3% of respondents. The profession or education of respondents did not have significance on their acceptance or rejection of PM. CONCLUSION: Awareness of prophylactic mastectomy is low among patients in this study. Education about breast cancer and methods of prevention need to be improved.

Clinical photography among African cleft caregivers.

OBJECTIVE: The aim of this paper is to document the practice of photography among clinicians whose daily work depends and is influenced so much by medical photography. MATERIALS AND METHODS: Questionnaires documenting the bio data, place of practice, and experience of cleft caregivers with clinical photography were distributed. Knowledge of rules guiding clinical photography and adherence to them were also asked. Types of camera used were documented and knowledge of the value of clinical photographs were also inquired. RESULTS: Plastic surgeons constitute the highest proportion of 27 (38.6%), followed by Oral and Maxillofacial surgeons with 14 (20.0%). Twenty one (30.0%) of the respondents always, 21 (30.0%) often, 12 (17.1%) frequently, while 9 respondents sometimes took photographs of their patients. Suggested uses of clinical photographs included training, 52 (74.3%), education, 51 (72.9%), medicolegal, 44 (62.9%) and advertisement, 44 (62.9%) among others. Twenty two (31.4%) did not know that there were standard guidelines for taking clinical photographs. Twenty three (32.9%) of them did not seek the consent of the patients before taking clinical photographs. CONCLUSION: While the practice of clinical photography is high among African cleft caregivers, there is a need for further education on the issues of standard rules and obtaining consent from patients.

Burden of prostate cancer in southwestern Nigeria.

OBJECTIVES: To determine the pattern of presentation, prevalent age, hospital incidence, and outcome of management of prostate cancer in our environment. METHOD: Patients with histopathology evidence of prostate cancer managed between January 1991 and December 2007 were studied. Information entered into a pro-forma sheet and analyzed included the age of patients, clinical features, investigations, histopathology diagnosis, outcome of management, and duration of follow-up. RESULTS: During the period, 189 patients aged 46-99 years (mean, 68.0; 9.8 SD) confirmed and managed for prostate cancer were studied. The average hospital incidence (2002-2004) was 182.5 per 10(5) male admissions with 15.1-month mean duration of symptoms. Most 178 (94.2%) patients presented with advanced diseases, with 1 or multiple complications in 172 (91.0%), obstructive lower urinary tract symptoms 156 (82.5%), distant metastasis 97 (51.3%), lower back pain 95 (50.3%), weight loss 95 (50.3%), hematuria 86 (45.5%), anemia 77 (40.7%), renal failure 74 (39.2%), and inability to walk 42 (22.2%). Eighty-nine (47.0%) patients were farmers, 111 (58.7%) indulged in alcohol, and 46 (24.3%) smoked cigarettes. Mean prostate-specific antigen results available in 53 patients was 106.0 ng/mL (187.2SD) and digital rectal examination was valuable in diagnosis. Adenocarcinoma (186 [98.4%]) was the main histopathology type and most patients 136 (71.9%) had bilateral orchidectomy with or without antiandrogens. Mean duration of follow-up was 83.7 weeks. CONCLUSIONS: The burden of prostate cancer in our developing community is worrisome. It is prevalent between 46 and 99 years in our community. Presentation is late, often with urinary retention and other complications. In our setting, treatment is still essentially palliative with orchidectomy, which we found to be beneficial, acceptable, and the most affordable to our patients.