Odontogenic tumors in Nigerian children and adolescents- a retrospective study of 92 cases

BACKGROUND: Tumours arising from odontogenic tissues are rare and constitute a heterogenous group of interesting lesions. The aim of this study was to determine the relative frequency of odontogenic tumors (OT) among Nigerian children and adolescents 19 years or younger. PATIENTS AND METHODS: The histopathology records were retrospectively reviewed for all the tumors and tumor-like lesions of the oral cavity and the jaws seen in children and adolescents ≤ 19 years seen between January 1980 and December 2003. Hematoxylin and eosin-stained sections were re-evaluated and the diagnosis in each case was confirmed or modified according to World Health Organization (WHO) classification, 1992; and were subjected to analysis of age, sex, site of tumor and histopathologic type. RESULTS: A total of 477 tumors and tumor-like lesions were seen in patients ≤ 19 years during the period of the study. Of these, 92 (19.3%) were odontogenic tumors. Benign odontogenic tumors constituted 98.9% of the cases seen, while only 1 case (1.1%) of malignant variety was seen during the period. The mean (SD) age of patients was 14.9 (± 3.1) years (range, 4–19 years). Male-to-female ratio was 1:1; and mandible-to-maxilla ratio was 2.7:1. OT's were most frequently seen in patients aged 16–19 years (46.7%) and the least number (2.2%) were found in patients aged 0–5 years. Among nine histologic types of OT seen, ameloblastoma (48.9%), adenomatoid odontogenic tumor (19.6%) and odontogenic myxoma (8.7%) were predominant. Multicystic/solid and unicystic variants of ameloblastoma were diagnosed in 40 (89%) and 5 (11%) cases respectively. CONCLUSIONS: Odontogenic tumors are relatively common in children and adolescents in Nigeria. One out of every 5 children and adolescents with tumors and tumor-like lesions of oral cavity and the jaws seen in this study had a diagnosis of odontogenic tumor

Perceptions and beliefs of community gatekeepers about genomic risk information in African cleft research

BACKGROUND: A fundamental ethical issue in African genomics research is how socio-cultural factors impact perspectives, acceptance, and utility of genomic information, especially in stigmatizing conditions like orofacial clefts (OFCs). Previous research has shown that gatekeepers (e.g., religious, political, family or community leaders) wield considerable influence on the decision-making capabilities of their members, including health issues. Thus, their perspectives can inform the design of engagement strategies and increase exposure to the benefits of genomics testing/research. This is especially important for Africans underrepresented in genomic research. Our study aims to investigate the perspectives of gatekeepers concerning genomic risk information (GRI) in the presence of OFCs in a sub-Saharan African cohort.METHODS: Twenty-five focus group discussions (FGDs) consisting of 214 gatekeepers (religious, community, ethnic leaders, and traditional birth attendants) in Lagos, Nigeria, explored the opinions of participants on genomic risk information (GRI), OFC experience, and the possibility of involvement in collaborative decision-making in Lagos, Nigeria. Transcripts generated from audio recordings were coded and analyzed in NVivo using thematic analysis.RESULTS: Three main themes-knowledge, beliefs, and willingness to act-emerged from exploring the perspective of gatekeepers about GRI in this group. We observed mixed opinions regarding the acceptance of GRI. Many participants believed their role is to guide and support members when they receive results; this is based on the level of trust their members have in them. However, participants felt they would need to be trained by medical experts to do this. Also, religious and cultural beliefs were crucial to determining participants' understanding of OFCs and the acceptance and utilization of GRI.CONCLUSIONS: Incorporating cultural sensitivity into public engagement could help develop appropriate strategies to manage conflicting ideologies surrounding genomic information in African communities. This will allow for more widespread access to the advances in genomics research in underrepresented populations. We also recommend a synergistic relationship between community health specialists/scientists, and community leaders, including spiritual providers to better understand and utilize GRI.</p

Novel <i>IRF6 </i>mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa

Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families

Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts

Abstract Introduction The frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large‐scale population genomic studies. The availability of data from the first whole‐genome sequencing for orofacial clefts in an African population motivated this investigation. Methods In total, 130 case‐parent trios were analyzed for SFs within the ACMG SFv.3.0 list genes. Additionally, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM). Results We identified 246 unique variants in 55 genes; five variants in four genes were classified as pathogenic or likely pathogenic (P/LP). The P/LP variants were seen in 2.3% (9/390) of the subjects, a frequency higher than ~1% reported for diverse ethnicities. On the ACMG list, pathogenic variants were observed in PRKAG (p. Glu183Lys). Variants in the PALB2 (p. Glu159Ter), RYR1 (p. Arg2163Leu) and LDLR (p. Asn564Ser) genes were predicted to be LP. Conclusion This study provides information on the frequency and pathogenicity of SFs in an African cohort. Early risk detection will help reduce disease burden and contribute to efforts to increase knowledge of the distribution and impact of actionable genomic variants in diverse populations

Novel <i>GREM1 </i>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. </jats:sec

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

Effect of age, impaction types and operative time on inflammatory tissue reactions following lower third molar surgery

<p>Abstract</p> <p>Background</p> <p>Postoperative mobidity following third molar surgery is affected by a number of factors. The study of these factors is essential for effective planning and limitation of morbidity. The aim of this study was to determine the effect of age, type of impaction and operative time on immediate postoperative tissue reactions following mandibular third molar surgery.</p> <p>Methods</p> <p>Consecutive patients with impacted mandibular third molar teeth were studied. All the third molars were classified according to Winter's classification. Surgical extraction was performed on all the patients by a single surgeon under local anaesthesia. The operation time was determined by the time lapse between incision and completion of suturing. Postoperative pain, swelling and trismus were evaluated.</p> <p>Results</p> <p>There were 120 patients with an age range of 19-42 years. Patients in the age range of 35-42 years recorded a lower pain score (p = 0.5) on day 1. The mouth opening was much better in the lower age group on day 2 and 5 (p = 0.007 and p = 0.01 respectively). Pain, swelling and trismus increased with increasing operative time. Distoangular impaction was significantly associated with higher VAS score on day 1 and 2 (p = 0.01, 0.0, 04). Distoangular and horizontal impaction are associated with a higher degree of swelling and reduced mouth opening on postoperative review days. Vertical impaction was associated with the least degree of facial swelling and best mouth opening.</p> <p>Conclusions</p> <p>Increasing operating time and advancing age are associated with more postoperative morbidity, likewise distoangular and horizontal impaction types.</p