Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Efficacy Of Microporous Tape In The Prevention Of Abnormal Post-Surgical Scars Among A Black Population.

BACKGROUND: A scar can be defined as a mark or a blemish resulting from a healed wound. All surgical incisions give rise to scars and approximately 15% have excessive scars. Some scars are thin lines which are almost unnoticeable, whereas others become abnormal when the amount of fibrosis is excessive or suboptimal or when it causes functional disability or aesthetic distress to the patient. The conversion of normal scarring to hypertrophic scarring occurs six to eight weeks after surgery as a result of increasing scar tension. Thus, scar support especially with the use of microporous tape is critical during this period. Objectives were to determine the efficacy of microporous tape in the prevention of abnormal post-surgical scars. METHODS: A randomized control study which compared the limb scar outcome between post-surgical patients who underwent scar taping with microporous tape and those who did not. The scars were assessed at six weeks, three months and six months after surgery using the Patient and Observer Scar Assessment Scale. The test group had microporous tape applied to their scars over a period of six months and worn twenty-four hours daily. The tapes were changed every fortnight or whenever they fell off. The data was analyzed using SPSS-22. The categorical variables, the relative scar height, the scar width and the OSAS score were compared using the Chi-square test and the independent t-test respectively. RESULTS: At six weeks, 48.8% of non-taped scars and 97.6% of taped scars were normal; at three months 75.6% of non-taped scars and 2.4% of taped scars were abnormal while at 6 months 80.5% of non-taped scars and none of the taped scars were abnormal. CONCLUSIONS: Microporous tape is an effective modality for preventing abnormal scarring in postsurgical patients.

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.

Surgical Reconstruction of Giant Penoscrotal Lymphedema in Sub-Saharan Africa.

OBJECTIVE: To present management challenges, surgical technique, and outcome associated with penoscrotal reconstruction in patients with giant scrotal lymphedema in sub-Saharan Africa. METHODS: A prospective study of all patients who had penoscrotal reconstruction for giant scrotal lymphedema at our university teaching hospital between January 2003 and December 2012 was carried out. Patients' preoperative clinical evaluation findings, operative technique, and postoperative course were reviewed after obtaining ethical approval and informed consent from the patients. RESULTS: Nineteen patients with giant scrotal lymphedema presented to us during the period of study; out of which, 11 had surgical excision and were studied. Their mean age and median duration of symptoms were 48.5 years and 11.5 years respectively. They all had surgical reconstruction using modified Charles procedure by the same combined team of urologists and plastic surgeons. Scrotal hematoma (27.3%) and superficial surgical site infection (18.2%) were complications encountered postoperatively. One patient (9.1%) had recurrence within 24 months, requiring repeat excision. CONCLUSION: Giant scrotal lymphedema poses severe physical challenge to the sufferer. Surgery remains the only hope to reduce penoscrotal size. Combined effort of urologic and plastic surgeons is essential for reconstruction.

Knowledge and cultural beliefs about the etiology and management of orofacial clefts in Nigeria's major ethnic groups.

OBJECTIVE: To determine the knowledge and cultural beliefs about the etiology and management of orofacial clefts in Nigeria's major ethnic groups. DESIGN: Questionnaires designed to elicit respondents' knowledge and cultural beliefs about the etiology and management of orofacial clefts. SETTING: Northern and southern Nigerian communities where the major ethnic groups reside. PARTICIPANTS: Consenting, randomly selected individuals. RESULTS: There were 650 respondents (350 women and 300 men) from 34 of Nigeria's 36 states; 65.5% were aged 21 to 40 years and 52.5% were married. There were Yoruba (33.7%), Igbo/Bini/Urhobo (40.5%), and Hausa/Fulani (25.8%), with most having attained primary and secondary education. Of those responding, 75% had seen an individual with an orofacial cleft. A significant level of ignorance about the cultural beliefs was found. The Hausa/Fulani considered it mostly an act of God; whereas, the Igbo/Bini/Urhobo and Yoruba groups displayed a greater variety of cultural beliefs. The latter groups implicated witchcraft, evil spirit or devil, the mother, and occasionally the child. Of respondents, 40% knew that surgery was a possible solution, and 22% would recommend a visit to the hospital. Respondents with higher educational attainment produced significantly more scientifically related etiologic factors and accurate treatment options. CONCLUSION: Of respondents, 75% were aware of the existence of orofacial clefts, and a fair knowledge of treatment of orofacial clefts was elicited. Diverse cultural beliefs often may present an obstacle to treatment. Improved awareness about the etiology and management of orofacial clefts is required.