Investigación en fisuras faciales: quo vadis España? / Investigation in facial fissures: quo vadis Spain?

Las fisuras orofaciales representan un grupo heterogéneo de malformaciones congénitas que afectan a distintas estructuras de la cavidad oral y de la cara. Globalmente, los bebés con estos trastornos presentan una mayor morbilidad y mortalidad a lo largo de su vida en comparación con individuos no afectados. Por ello, los avances en la investigación biomédica resultan ineludibles. Así, el objetivo general de este trabajo fue llevar a cabo una revisión bibliográfica para analizar narrativamente los 10 principales estudios primarios sobre fisuras orofaciales llevados a cabo en España, publicados del 2018 hasta la actualidad. Según esto, a nivel institucional, destaca la Universidad Complutense de Madrid (UCM) con cuatro artículos publicados por el grupo de investigación UCM 920202. También sobresale la Universidad Rey Juan Carlos de Madrid, con tres artículos relacionados con diferentes aspectos de la personalidad y la calidad de vida de los pacientes fisurados, así como otras muchas variables cognitivo-emocionales. En relación con la Universidad de Valencia, encontramos dos artículos llevados a cabo en amplias muestras de pacientes con fisuras. Por último, en Barcelona resulta destacable un estudio observacional sobre problemas otorrinolaringológicos en pacientes operados de fisura palatina. En conclusión, si bien en los últimos años se han publicado varios artículos sobre distintos aspectos relacionados con las fisuras, aún queda mucho trabajo por hacer. España debería seguir potenciando proyectos con líneas de trabajo centradas en estas alteraciones del desarrollo craneofacial. Se necesitan estudios amplios, multicéntricos y colaborativos, para ahondar en los mecanismos etiológicos y, en última instancia, en las posibles herramientas para su prevención. Del mismo modo, se necesitan ayudas para dilucidar mejor las cuestiones relacionadas con los tratamientos en todas las dimensiones de la salud, preferentemente a partir de ensayos clínicos controlados aleatorizados, que faciliten la traslación de conocimientos y su accesibilidad universal dentro del sistema sanitario público español.

SUMMARY: Orofacial clefts represent a heterogeneous group of congenital malformations affecting different structures of the oral cavity and face. Overall, infants with these disorders have a higher lifetime morbidity and mortality compared to unaffected individuals. Therefore, advances in biomedical research are unavoidable. Thus, the overall objective of this work was to conduct a literature review to narratively analyse the 10 main primary studies on orofacial clefts carried out in Spain, published from 2018 to date. According to this review, at an institutional level, the Complutense University of Madrid (UCM) is notable with 4 articles published by the UCM 920202 research group. The Rey Juan Carlos University of Madrid also stands out, with three papers related to different aspects of the personality and quality of life of cleft patients, as well as many other cognitive-emotional variables. In relation to the University of Valencia, we found two studies carried out on large samples of cleft patients. Finally, in Barcelona, an observational study on otorhinolaryngological problems in cleft palate patients is noteworthy. In conclusion, although several studies have been published in recent years on different aspects related to clefts, there is still much work to be done. Spain should craniofacial development. Large, multicenter and collaborative studies are needed to delve deeper into the aetiological mechanisms and, ultimately, into the possible tools for their prevention. Similarly, support is needed to better elucidate questions related to treatments in all dimensions of health, preferably randomised controlled clinical trials, which facilitate the transfer of knowledge and its universal accessibility within the Spanish public health system.

Transverse Facial Cleft, Tessier number 7: Case Report of a Rare Congenital Anomaly

@#Transverse facial cleft (TFC), Tessier number 7, is a rare congenital anomaly commonly associated with other anomalies of the first and second branchial arch with varying severity. Risk factors such as alcohol abuse, folic acid deficiency, and ingestion of herbal concoctions in pregnancy have been implicated in this deformity. We report a case of a bilateral transverse facial cleft in a newborn and review the existing literature on the condition to increase awareness and knowledge.

IRF6 polymorphisms in Brazilian patients with non-syndromic cleft lip with or without palate / Polimorfismos do gene IRF6 em pacientes brasileiros com fenda labial não sindrômica com ou sem fenda palatina

Abstract Introduction: Non-syndromic orofacial clefts have a complex etiology due to the contribution from both genetic and environmental risk factors, as well as the interaction between them. Among the more than 15 susceptibility loci for non-syndromic orofacial clefts with considerable statistical and biological support, the IRF6 is the most validated gene by the majority of studies. Nonetheless, in genetically heterogeneous populations such as Brazilian, the confirmation of association between non-syndromic orofacial clefts and IRF6 common variants is not a consolidated fact and unrecognized IRF6 variants are poorly investigated. Objective: The aim of this study was to investigate the association of IRF6 polymorphisms with non-syndromic orofacial clefts development in a population from northeast Brazil. Methods: Blood samples of 186 non-syndromic orofacial clefts patients and 182 controls from Rio Grande do Norte, Brazil, were obtained to analyze IRF6 polymorphisms (rs2235371, rs642961, rs2236907, rs861019, and rs1044516) by real-time polymerase chain reaction. Non-syndromic orofacial clefts patients were classified in cleft lip and palate, cleft palate only and cleft lip only groups. Results: The genotype and allele frequencies of single nucleotide polymorphism rs2235371 in IRF6 showed significant differences in patients with cleft palate when compared to the controls, whereas no association was shown between rs642961, rs2236907, rs861019, and rs1044516 and non-syndromic orofacial clefts. Conclusion: The association found between rs2235371 and isolated cleft palate should be interpreted with caution due to the low number of individuals investigated, and more studies with larger sample size are needed to confirm these association. In addition, there is a lack of association of the rs642961, rs2236907 and rs861019 polymorphisms with non-syndromic orofacial clefts susceptibility.

Resumo Introdução: As fendas orofaciais não sindrômicas possuem uma etiologia complexa devido à contribuição de fatores de risco genéticos e ambientais, assim como a interação entre eles. Dentre os mais de 15loci de susceptibilidade para as fendas orofaciais não sindrômicas com considerável suporte estatístico e biológico, o IRF6 é o gene mais validado pela maioria dos estudos. Apesar disso, em populações geneticamente heterogêneas como a brasileira, a confirmação da associação entre as fendas orofaciais não sindrômicas e as variantes mais comuns do IRF6 ainda não é um fato consolidado e outras variantes não tão conhecidas IRF6 são pouco investigadas. Objetivo: O objetivo deste estudo foi investigar a associação de variados polimorfismos do IRF6 com o desenvolvimento das fendas orofaciais não sindrômicas em uma população do nordeste do Brasil. Método: Amostras de sangue de 186 pacientes com fendas orofaciais não sindrômicas e 182 controles do estado do Rio Grande do Norte, Brasil, foram obtidas para analisar os polimorfismos do IRF6 (rs2235371, rs642961, rs2236907, rs861019 e rs1044516) por reação em cadeia da polimerase em tempo real. Os pacientes com fendas orofaciais não sindrômicas foram classificados em fenda labiopalatina, fenda palatina isolada e fenda labial isolada. Resultados: As frequências genotípica e alélica do polimorfismo de único nucleotídeo rs2235371 no IRF6 mostraram-se significativamente diferentes em pacientes com fenda palatina isolada quando comparadas às dos controles, enquanto que nenhuma associação foi encontrada entre rs642961, rs2236907, rs861019 e rs1044516 e risco para o desenvolvimento das fendas orofaciais não sindrômicas. Conclusão: A associação encontrada entre rs2235371 e fenda palatina isolada deve ser interpretada com cautela devido ao baixo número de indivíduos investigados, sendo necessários mais estudos com um tamanho amostral maior para confirmar essa associação. Além disso, não foram encontradas associações significativas entre os demais polimorfismos do IRF6 rs642961, rs2236907, rs861019 e rs1044516 e a susceptibilidade às fendas orofaciais não sindrômicas.

Demographics and Clinical Profile of Orofacial Cleft in International Islamic University Malaysia from 2009 until 2018

@#Orofacial clefts (OFC) are the most common craniofacial anomalies. There is no published data regarding the demographic of OFC cases seen in International Islamic University Malaysia (IIUM), since the establishment of the IIUM Multi-Disciplinary Cleft Team (IIUM-MDCT). The present study aimed to build a database on demographic profile of OFC cases seen in IIUM from 2009 until 2018. Data from all registered OFC cases were obtained from the medical records. Birth prevalence was tabulated against the population statistics for the period, obtained from the Department of Statistics Malaysia. A total of 20 cases were seen over the period of nine years. The registry recorded about 60% of females and 40% of males. Age distribution was 40% below the age of 10 years old, 40% between 11 to 20 years old and 20% of 21 years old and above. As for race, 90% were Malay, 5% were Chinese and Indian, respectively. Majority of patients (75%) were from Kuantan, 10% from Kemaman and 5% from Pekan, Kuala Terengganu and Kota Bharu, respectively. The most common OFC was cleft lip and palate (80%), followed by cleft palate (15%) and facial cleft (5%). The LAHSHAL classification was recorded with 75% of cases were unilateral, of which 73% affecting the left side. Other health anomalies were recognised in 45% of cases and 20% of them has family history of cleft. The present study could provide a baseline information on the status of OFC patients seen by IIUM-MDCT.

Profile of Cleft Lip and Cleft Palate at a Public Hospital in Southern India

Objective: To analyze the pattern of cleft lip and cleft palate cases and their operativemanagement at a tertiary-care hospital. Methods: Data of all patients (<18 year) with cleft lipand cleft palate operated between 2011 and 2016 were extracted from the records andanalyzed. Results: The final analysis included1643 cases (60.9% males). Mean (SD) age atthe time of surgery was 8.9 (10.17) years. Left-sided cleft clip was more common. Completehard palate type of cleft palate on left was present in 787 (47.90%). Primary Cleft Palaterepair was most common procedure (492, 29.9% children, followed by primary lip noseunilateral in 458 (27.9%) and lip nose revision in 298 (21.1%). Conclusion: Data on age atpresentation and procedures used for correction of cleft lip and cleft palate are presented.

Orofacial dysfunction in cleft and non-cleft patients using nordic orofacial test - a screening study

Abstract Cleft lip, alveolus and palate is a congenital malformation caused by the lack of fusion of the lip and palate embryonic processes, which may disrupt the main functions of the stomatognathic system. Aim: This study aimed to assess the orofacial dysfunction in individuals with cleft lip, alveolus, and palate compared to non-cleft patients. One hundred and twenty individuals between 32 and 65 years of age were selected in the Craniofacial Center and in the School of Dentistry and divided into two groups: non-cleft patients (N-CLAP) and cleft lip, alveolus, and palate patients (CLAP). The two groups were matched by gender. Each individual was interviewed and submitted to a clinical evaluation during which the NOT-S was used to assess orofacial dysfunction. To verify the intra-examiner agreement, the values were compared using the Kappa test. The Mann-Whitney test compared performance on the NOT-S between the groups. The Chi-Square test compared the NOT-S domains between the groups. A comparison of the NOT-S scores between the groups revealed statistically significant differences in gender (p<0.001), but no statistically significant differences in the intragroup gender comparison were found. The assessment of the NOT-S domains between the N-CLAP and CLAP groups exhibited statistically significant differences in domains: breathing (p=0.021), chewing and swallowing (p<0.001), and dryness of the mouth (p=0.002) of the interview and significant differences in all domains of the clinical examination (p<0.001). Individuals with CLAP showed more orofacial dysfunction than non-cleft patients, without gender differences, after being assessed through the NOT-S.

Resumo A fissura de lábio, alvéolo e palato é uma malformação congênita causada pela falta de fusão dos processos embrionários labial e palatino, que podem comprometer as principais funções do sistema estomatognático. Utilizando o Nordic Orofacial Test - Screening (NOT-S), este estudo transversal observacional, objetivou avaliar a presença da disfunção orofacial nos indivíduos com fissura de lábio, alvéolo e palato em relação a indivíduos sem fissura ou anomalia craniofacial. Cento e vinte indivíduos entre 32 e 65 anos de idade foram selecionados e divididos em dois grupos: pacientes sem fissura labiopalatina (N-CLAP) e pacientes com fissura de lábio, alvéolo e palato (CLAP). Os dois grupos foram combinados por gênero. Cada indivíduo foi entrevistado e submetido a uma avaliação clínica durante a qual o NOT-S foi utilizado para avaliar a disfunção orofacial. O teste de Mann-Whitney comparou desempenho no NOT-S entre os grupos. O teste Qui-Square comparou os domínios NOT-S entre os grupos. A concordância intra-examinador foi K=0,75. Uma comparação dos escores de NOT-S entre os grupos revelou diferenças estatisticamente significativas no gênero (p<0,001), mas não foram encontradas diferenças estatisticamente significativas na comparação de gênero intragrupo. A avaliação dos domínios de NOT-S entre os grupos N-CLAP e CLAP apresentou diferenças estatisticamente significativas nos domínios II (p=0,021), IV (p<0,001) e VI (p=0,002) da entrevista e diferenças significativas em todos os domínios do exame clínico (p<0,001). Indivíduos com CLAP apresentaram maior presença de disfunção orofacial do que os indivíduos sem fissura labioapalatina, conforme avaliado pelo NOT-S.

Research progress in environmental factors of nonsyndromic orofacial clefts / 中华整形外科杂志

Nonsyndromic orofacial clefts (NSOC) is a common but complicated congenital malformation, resulted from complex interplay of genetic and environmental factors. In this study, certain environmental factors was demonstrated, including drug, supplementation intake, occupational exposure, environmental pollution and psychosocial factor, to be associated with increasing risk of NSOC.

IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population / Polimorfismo de nucleotídeo único do gene IRF6 rs2235375 está associado com à fenda palatina isolada não sindrômica, mas não com fenda labial com ou sem fenda palatina em população do sul da Índia

Abstract Introduction Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. Objective We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. Methods 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. Results There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p = 0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p = 0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p = 0.005). Conclusion These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.

Resumo Introdução Fatores de transcrição constituem uma família de proteínas muito diversa envolvida na ativação ou repressão da transcrição de um gene, em um determinado momento. Vários estudos usando modelos animais demonstraram o papel dos genes do fator de transcrição no desenvolvimento craniofacial. Objetivo Nosso objetivo foi investigar a associação do polimorfismo IRF6 intron-6 na fenda labial não sindrômica com ou sem fenda palatina em uma população do sul da Índia. Método Um total de 173 pacientes com fenda labial não sindrômica com ou sem fenda palatina e 176 controles sem fendas foram genotipados para a variante IRF6 rs2235375 por amplificação alelo-específica utilizando o sistema KASPar de genotipagem de polimorfismo de nucleotídeo único. A associação entre o polimorfismo de nucleotídeo único Fator 6 Regulatório do Interferon (IRF6) intron-6 dbSNP208032210:g.G>C (rs2235375) e o risco de fenda labial não sindrômica com ou sem fenda palatina foi investigado pelo teste qui-quadrado. Resultados Houve diferenças significativas nas frequências de genótipos ou alelos do rs2235375 SNP entre controles e casos com fenda labial não sindrômica com ou sem fenda palatina. A variante IRF6 rs2235375 foi significativamente associada ao aumento do risco de fenda labial não sindrômica com ou sem fenda palatina em modelos codominantes, dominantes (OR: 1,19; IC 95%: 1,03-2,51; p = 0,034) e alélicos (OR: 1,40; IC 95%: 1,04-1,90; p = 0,028). Quando a análise do subgrupo foi realizada, um risco significativamente aumentado foi observado no grupo Fenda Palatina Isolada (OR dominante: 4,33; IC 95%: 1,44-12,97; p = 0,005). Conclusões Esses resultados sugerem que o polimorfismo de nucleotídeo único IRF6 rs2235375 desempenha um papel importante na patogênese e no risco de desenvolvimento de fenda labial não sindrômica com ou sem fenda palatina.

The structure of disease among children department of maxillofacial surgery / Монголын Анагаах Ухаан

Introduction@#The department of Maxillofacial surgery of the National Center for Maternal and Child Health (NCMCH) has a nationwide tertiary medical service on the patients who is with congenital orofacial anomalies, facial injury, nonmalignant tumors of this area, and inflammations of maxillofacial area following dental caries and other reasons as well. For the last years nationwide the number of inpatient of the department has been growing constantly meaning that the necessity of medical care for our countries for children is also growing. Therefore by studying and analyzing the structure of the illness of the department will be able to determine the most frequent orofacial illness among children in our country, to prevent them, define the treatment plan.@*Aim@#To clarify what disease in the Maxillofacial area mainly occurs among Mongolian children. @*Materials and Method@#We included all patients who underwent emergency and planned surgery in the department of Max-illofacial surgery, NCMCH between 2014-2015. </br> We used descriptive and case-control method based on the information of inpatients history record between 2014.01.01-2015.01.01 at the department of Maxillofacial surgery, NCMCH and using our own –designed, pre-screened survey card. </br> Statistical data processing is done using Microsoft Office-2017 and SPSS for windows programs, and the results are shown illustrated method. The survey identified the incidence and frequency of each disease classification, and analyzed the characteristics of the child’s age, sex, and residency.@*Result@#The most of patients, who involved in this study were with the inflammation of maxillofacial area (57%), and the congenital orofacial clefts (24.4%). </br> In total 3300 children from 0-18 years old admitted at the department of Maxillofacial surgery and Infants study for orofacial surgery treatment were involved in this study. </br> Among which were 1803(54.6%) male, 1497(45.4%) female. Considering the residency, 2525(76.5%) children from Ulaanbaatar and 775 (23.5%) children from countryside. The most of patients, who involved in this study, were with the inflammation of maxillofacial area (57%), and the congenital orofacial clefts (24.4%).@*Conclusion@#Based on the result of our study the highest incidence among the participants was inflammation of maxillofacial area with 57% in which odontogenic periostitis was the most frequent with 21.6%. Congenital orofacial clefts and disorders was the 2^nd most frequent with 24.4%. Inflammation of maxillo-facial area was most frequent in 0-2 age group with 33.7%, and mostly in male. Considering there were residency with 83.2% highest in Ulaanbaatar and mostly in Bayanzurkh district with 24.7%.

Prevalence of orofacial clefts in Korean live births

OBJECTIVE: The aim of this study was to investigate the prevalence of orofacial clefts and identify the characteristics of other birth defects associated with orofacial clefts in Korea. METHODS: This study used data from the Congenital Anomaly Survey conducted by the Korea Institute for Health and Social Affairs. The survey was conducted on birth defects documented during 2005 to 2006 in 2,348 medical institutes in Korea. This study was performed using data from medical insurance claims of the National Health Insurance Corporation. The prevalence of orofacial clefts was defined as the number of cases per 10,000 live births. RESULTS: Among the 883,184 live births, 25,335 infants had birth defects, which included 980 infants with orofacial clefts. The prevalence of total orofacial clefts in the total live births was 11.09 per 10,000, accounting for 3.9% of all birth defects. The most common orofacial cleft was cleft palate only (n=492), followed by cleft lip only (n=245) and cleft lip with cleft palate (n=243), with prevalence rates of 5.57, 2.77, 2.75 per 10,000 live births, respectively. While malformations of the circulatory system; digestive system; eyes, ears, face, and neck; and musculoskeletal system were most frequently encountered among infants with a cleft lip with or without a cleft palate, anomalies of most organ systems were notably observed among infants with cleft palate only. CONCLUSION: The prevalence of orofacial clefts in Korea was similar or slightly lower than that of other countries. This study informs present status of orofacial clefts and gives baseline data to lay the foundation stone for Korea's registry system of orofacial clefts.

Family care practitioners experience with individuals with orofacial clefts in Brazil / Experiência de profissionais de saúde da família com pessoas com fendas orofaciais no Brasil

INTRODUCTION: Orofacial clefts are among the most prevalent birth defects worldwide. Specialized treatment and surveillance of basic health needs are critical. Few studies have investigated primary care practitioners' experience in caring for individuals with clefts. OBJECTIVE: It was to describe experience and current interest of family care practitioners on the management of individuals with clefts. METHODS: Observational cohort of 104 practitioners from Maceió (AL) e Campinas (SP). Demographic, academic and professional characteristics, didactic experience and desire in continuing education on clefts were assessed using a questionnaire RESULTS:Seventy-four practitioners were located in Maceió and 30 in Campinas. Female gender and low academic qualification were predominant. Physicians and nurses prevailed over dentists, 78 (75%) participants had clinical experience with clefts. Use of protocols was mentioned by 3/104 (2.9%), provision of information on clefts by 58/104 (56%) and referrals to the Brazilian Reference Network by 7/104 (6.7%). Almost 50% reported didactic experience and 94%, desire on continuing education in this field CONCLUSION: Results corroborate the literature and reinforce the need of improving family care practitioners' skills to manage individuals with clefts. Education and strengthen ties between primary level of the health system and specialized teams must be focused. Some strategies are presented in this regard.

INTRODUÇÃO: As fendas orofaciais estão entre os mais prevalentes defeitos congênitos em todo o mundo. Atenção especializada e vigilância de necessidades básicas de saúde são críticas no cuidado aos indivíduos. OBJETIVO: Foi descrever a experiência e o interesse de profissionais da Estratégia Saúde da Família no acompanhamento de indivíduos com fendas orofaciais. MÉTODOS: Coorte observacional com 104 profissionais de Maceió (AL) e Campinas (SP). Características demográficas, acadêmicas e profissionais, bem como a experiência didática e o desejo por educação continuada, foram colhidas por meio de questionário. RESULTADOS: Setenta e quatro profissionais atuavam em Maceió e 30 em Campinas. O gênero feminino e a baixa qualificação acadêmica foram predominantes. Médicos e enfermeiros prevaleceram sobre dentistas, e 78 (75%) participantes tinham experiência clínica com fendas. O uso de protocolos foi mencionado por 3/104 (2,9%), a oferta de informações sobre fendas por 58/104 (56%) e o encaminhamento para unidades especializadas da Rede de Referência por 7/104 (6,7%). Cerca de 50% dos participantes referiram experiência didática e 94%, desejo por educação continuada CONCLUSÃO: Os resultados corroboram a literatura e reforçam a necessidade de melhorar a capacitação de profissionais nesta área. Para tanto, são apresentadas estratégias para promover educação e reforçar laços entre a atenção básica e equipes especializadas.

Lack of mutations in the PVRL3 gene in North American caucasians with non-syndromic cleft lip/palate

Cleft lip with or without cleft palate (CLP) is one of the most common birth defects. In about 70 percent of cases, CLP occurs as an isolated anomaly, denoted non-syndromic CLP (nsCLP). Genetic linkage and association studies have implicated many loci in susceptibility to nsCLP, including some members of the nectin gene family. We performed mutation screening of the PVRL3 gene that encodes nectin-3 in 73 unrelated Caucasian nsCLP patients and 105 unrelated controls from North America. We detected no sequence variants in the PVRL3 gene in either the nsCLP patients or the controls. These data suggest that PVRL3 is not an important susceptibility gene for nsCLP in the North American Caucasian population.

Genetics of cleft lip and palate: A review

Orofacial clefts, particularly non-syndromic cleft lip with or without cleft palate (CL/P) are the most common craniofacial deformities, affecting one in every 700 to 1000 newborns worldwide. Numerous efforts have been made to understand the etiology of CL/P so as to predict its occurrence and to prevent it from occurring in the future. In the recent years, advances in genetics and molecular biology have begun to reveal the basis of craniofacial development. Various genetic approaches, including genome-wide and candidate gene association studies as well as linkage analysis, have been undertaken to identify aetiologic factors, but results have often been inconclusive or contradictory. These results may support the presence of aetiologic heterogeneity among populations and the presence of multiple genes involved in the aetiology of CL/P. Despite these difficulties, several different genes have been implicated in harbouring genes that contribute to the aetiology of CL/P. In conclusion, the genetic basis of CL/P is still controversial because of genetic complexity of clefting.