Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification

Background/Aim: Orofacial clefts are the most common birth defect of the head. Clefts arise due to a lack of tissue fusion during prenatal development. Various factors can cause the absence of fusion of these structures during 6-8th week of embryonic development. It is proven that the cause of non-s...

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Main Authors: Puškar Nataša, Jakovljević Aleksandar, Simić Radoje, Nikolić Nađa, Miljanović Milica, Arsić Ivan, Petrović Đorđe, Đerlek Amar, Nedeljković Nenad
Format: Article
Language:English
Published: Balkan Stomatological Society 2025-01-01
Series:Balkan Journal of Dental Medicine
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Online Access:https://scindeks-clanci.ceon.rs/data/pdf/2335-0245/2025/2335-02452502081P.pdf
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author Puškar Nataša
Jakovljević Aleksandar
Simić Radoje
Nikolić Nađa
Miljanović Milica
Arsić Ivan
Petrović Đorđe
Đerlek Amar
Nedeljković Nenad
author_facet Puškar Nataša
Jakovljević Aleksandar
Simić Radoje
Nikolić Nađa
Miljanović Milica
Arsić Ivan
Petrović Đorđe
Đerlek Amar
Nedeljković Nenad
author_sort Puškar Nataša
collection DOAJ
description Background/Aim: Orofacial clefts are the most common birth defect of the head. Clefts arise due to a lack of tissue fusion during prenatal development. Various factors can cause the absence of fusion of these structures during 6-8th week of embryonic development. It is proven that the cause of non-syndromic orofacial clefts (NSOFCs) has multifactorial etiology. This review aims to provide a comprehensive summary on etiology and classification of NSOFCs. Material and Methods: Online bibliographic databases were utilized in order to find as many as possible available studies that showed a connection between any environmental factor and genes and NSCL/P, also available studies and books which represented any NSOFC classification system. Results: From the 35 articles and books reviewed, key etiological factors and numerous classification systems that developed over time have been identified. While the multifactorial nature is well-established and proven, specific percentage contributions of individual factors, either environmental or genetic, remain inconclusive. No single classification system is considered perfect, underscoring the need for continued research. Conclusions: Existing classification systems for NSOFCs all have advantages and disadvantages, lacking universal ease of use and comprehensiveness. However, they reflected the evolving understanding of NSOFCs, progressing from anatomical to embryological and developmental perspectives. While several potential etiological factors have been identified, the precise etiology of NSOFCs remain unclear due to complex interplay of factors involved in their occurrence. A definitive cause has not yet been identified.
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spelling doaj-art-74bce28faad141ef8801a979be6445382025-08-20T03:43:20ZengBalkan Stomatological SocietyBalkan Journal of Dental Medicine2335-02452025-01-01292818910.5937/bjdm2502081P2335-02452502081PUnraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classificationPuškar Nataša0Jakovljević Aleksandar1https://orcid.org/0000-0001-6512-4934Simić Radoje2https://orcid.org/0009-0008-0824-951XNikolić Nađa3https://orcid.org/0000-0002-8513-9313Miljanović Milica4Arsić Ivan5https://orcid.org/0009-0001-4966-9288Petrović Đorđe6Đerlek Amar7Nedeljković Nenad8https://orcid.org/0000-0002-4523-9504University of Novi Sad, Faculty of Medicine, Clinic of Dentistry of Vojvodina, Department of Jaw Orthopedics, SerbiaUniversity of Belgrade, School of Dental Medicine, Department of Pathophysiology, Belgrade, SerbiaInstitute for Mother and Child Health Care of Serbia, Department of Plastic and Reconstructive Surgery, New Belgrade, SerbiaUniversity of Belgrade, School of Dental Medicine, Laboratory for Basic Science, Belgrade, SerbiaUniversity of Novi Sad, Faculty of Medicine, Clinic of Dentistry of Vojvodina, Department of Oral Surgery, SerbiaUniversity of Belgrade, School of Dental Medicine, Department of Orthodontics and Dentofacial Orthopedics, SerbiaUniversity of Novi Sad, Faculty of Medicine, Clinic of Dentistry of Vojvodina, Department of Jaw Orthopedics, SerbiaUniversity of Belgrade, School of Dental Medicine, Department of Orthodontics and Dentofacial Orthopedics, SerbiaUniversity of Belgrade, School of Dental Medicine, Department of Orthodontics and Dentofacial Orthopedics, SerbiaBackground/Aim: Orofacial clefts are the most common birth defect of the head. Clefts arise due to a lack of tissue fusion during prenatal development. Various factors can cause the absence of fusion of these structures during 6-8th week of embryonic development. It is proven that the cause of non-syndromic orofacial clefts (NSOFCs) has multifactorial etiology. This review aims to provide a comprehensive summary on etiology and classification of NSOFCs. Material and Methods: Online bibliographic databases were utilized in order to find as many as possible available studies that showed a connection between any environmental factor and genes and NSCL/P, also available studies and books which represented any NSOFC classification system. Results: From the 35 articles and books reviewed, key etiological factors and numerous classification systems that developed over time have been identified. While the multifactorial nature is well-established and proven, specific percentage contributions of individual factors, either environmental or genetic, remain inconclusive. No single classification system is considered perfect, underscoring the need for continued research. Conclusions: Existing classification systems for NSOFCs all have advantages and disadvantages, lacking universal ease of use and comprehensiveness. However, they reflected the evolving understanding of NSOFCs, progressing from anatomical to embryological and developmental perspectives. While several potential etiological factors have been identified, the precise etiology of NSOFCs remain unclear due to complex interplay of factors involved in their occurrence. A definitive cause has not yet been identified.https://scindeks-clanci.ceon.rs/data/pdf/2335-0245/2025/2335-02452502081P.pdforofacial cleftcleft lipcleft palatecleft lip and palateetiologyclassification
spellingShingle Puškar Nataša
Jakovljević Aleksandar
Simić Radoje
Nikolić Nađa
Miljanović Milica
Arsić Ivan
Petrović Đorđe
Đerlek Amar
Nedeljković Nenad
Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification
Balkan Journal of Dental Medicine
orofacial cleft
cleft lip
cleft palate
cleft lip and palate
etiology
classification
title Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification
title_full Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification
title_fullStr Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification
title_full_unstemmed Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification
title_short Unraveling the cleft: A historical and comparative review of non-syndromic orofacial cleft etiology and classification
title_sort unraveling the cleft a historical and comparative review of non syndromic orofacial cleft etiology and classification
topic orofacial cleft
cleft lip
cleft palate
cleft lip and palate
etiology
classification
url https://scindeks-clanci.ceon.rs/data/pdf/2335-0245/2025/2335-02452502081P.pdf
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