Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry.

BACKGROUND: Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been made in understanding OFCs, due to advances in sequencing and genotyping technologies. Despite these advances, very little is known about the genetic interplay in the Malagasy population. METHODS: Here, we performed high-resolution whole-exome sequencing (WES) on non-syndromic cleft lip with or without palate (nCL/P) trios in the Malagasy population (78 individuals from 26 families (trios)). To integrate the impact of genetic ancestry admixture, we computed both global and local ancestries. RESULTS: Participants demonstrated a high percentage of both African and Asian admixture. We identified damaging variants in primary cilium-mediated pathway genes WNT5B (one family), GPC4 (one family), co-occurrence in MSX1 (five families), WDR11 (one family), and tubulin stabilizer SEPTIN9 (one family). Furthermore, we identified an autosomal homozygous damaging variant in PHGDH (one family) gene that may impact metabiotic activity. Lastly, all variants were predicted to reside on local Asian genetic ancestry admixed alleles. CONCLUSION: Our results from examining the Malagasy genome provide limited support for the hypothesis that germline variants in primary cilia may be risk factors for nCL/P, and outline the importance of integrating local ancestry components better to understand the multi-ethnic impact on nCL/P.

Long-Term Impact of a Mission-Based Surgical Training Rotation on Plastic Surgery Capacity Building in Rwanda.

OBJECTIVE: Short-term, high-volume surgical training experiences can lead to successful skills transfer and be an effective method of training surgical providers in low-resource settings. However, immediate skills acquisition does not guarantee long-term performance of surgical procedures by trainees. This study aims to determine the long-term impact of a short-term plastic surgery training rotation (STR) on general surgeon contribution to plastic surgery capacity building in Rwanda. DESIGN: A retrospective survey study was conducted. Surveys were distributed to credentialed general surgeons who previously participated in the Operation Smile STR in Rwanda. Questions focused on exposure to procedures during the rotation and current practice demographics. The percentage of current practice volumes dedicated to plastic surgery was mapped to demonstrate participant contribution to plastic surgery capacity in the country. SETTING: Surveys were distributed remotely. Surgeon respondents previously participated in the STR at the Rwinkwavu District Hospital, a primary level hospital in eastern Rwanda. PARTICIPANTS: All 8 prior participants of the STR who completed residency and are currently practicing as general surgeons in Rwanda were included. RESULTS: Six out of 8 prior participants completed the survey (75.0%). All respondents work as general surgeons in governmental hospitals around the country. Up to 75% of surgeon caseloads are dedicated to plastic surgery procedures. Half of respondents work in regions without a credentialed plastic surgeon. Exposure to cleft and congenital hand surgery during the rotation did not lead to durable performance in practice. All participants felt the rotation improved their performance in multiple core competencies. CONCLUSION: Participation in a short-term plastic surgery training experience in Rwanda was associated with increased long-term surgical capacity in the country through a task-sharing model. A mission-based rotation may provide sufficient exposure for basic plastic surgery procedures, but does not provide enough volume or time to durably teach more complicated surgeries such as cleft repair. Further studies are needed to determine how longer durations of training exposure impacts long-term performance of plastic surgery procedures.