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Open research questions in Cleft Lip and Palate Research

343 gap statements mined from Cleft Lip and Palate Research papers in our 7.9M-paper local library, which holds 3,232 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Feeding difficulties are a major challenge for infants with CLP. Prolonged feeding times and poor weight gain are significant concerns. The study identifies the need for early multidisciplinary support for CLP patients as a challenge.

    Nasoalveolar Molding and Feeding in Infants with Cleft Lip and Palate: An Exploratory Study of Parents’ and Caregivers’ Perceived Experiences · 2026 · DOI

  • There is a need to evaluate the effectiveness of NAM therapy in improving feeding outcomes in CLP patients. The study identifies a gap in understanding the perceptions of parents and caregivers on the potential of NAM to improve feeding.

    Nasoalveolar Molding and Feeding in Infants with Cleft Lip and Palate: An Exploratory Study of Parents’ and Caregivers’ Perceived Experiences · 2026 · DOI

  • The exact mechanism of action of the SARS-CoV-2 virus on the occurrence of these anomalies is unknown. The combination of hypoglossia, micrognathia, and situs inversus totalis is extremely rare.

    Newborn with Hypoglossia and Micrognathia with Situs Inversus Totalis Born to Mothers with SARS-CoV-2 Infection: A Case Report · 2025 · DOI

  • To the best of our knowledge, the SIR following palatal graft harvesting has not been previously investigated.

    Systemic inflammatory acute-phase response following palatal graft harvesting in rats · 2026 · DOI

  • Given their large size, they can have an outsized effect on phenotype, however, the contribution of SVs to the genetic architecture of orofacial clefts (OFCs) is not well understood.

    Characterization of de novo structural variants in trios with orofacial clefts · 2026 · DOI

  • Future studies are required to understand the differences in CL/P mortality rates across various sociodemographic groups.

    Cleft lip and/or palate mortality trends in the USA: a retrospective population-based study · 2024 · DOI

  • The case demonstrates BFP flap success in very advanced age with geriatric constraints such as frailty and limited anesthetic tolerance, but broader clinical evidence from comparative studies across elderly populations is needed.

    Reconstruction of a partial maxillectomy defect using a pedicled buccal fat pad flap in an elderly oral squamous cell carcinoma patient · 2026 · DOI

  • The complex interactions between various cellular and molecular events in palatogenesis are not fully understood. The mechanisms underlying cleft palate development are not fully elucidated.

    Multiscale Convergence of Signaling, Epigenetic, and Environmental Networks in Mammalian Palatogenesis and Cleft Palate Pathogenesis · 2026 · DOI

  • Gaps in standardized mental health assessment and limited integration of psychological services remain evident.

    Mental Health Challenges in Cleft Lip and/or Palate Care: A Narrative Review with an Indian Perspective · 2026 · DOI

  • American Indian and Alaska Native (AI/AN) children are disproportionately affected by orofacial clefts, yet access to comprehensive cleft and craniofacial care has not been systematically quantified.

    Mapping Disparities In Access To Cleft And Craniofacial Care For American Indian And Alaska Native Populations · 2026 · DOI

  • The genetic etiology of OFC subtypes is not well understood. The biological mechanisms differentiating each subtype and syndromic forms are still poorly understood.

    Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease · 2026 · DOI

  • The communication between oral and nasal cavities results in inadequate generation of negative pressure required for suckling. The impression making process can be challenging due to lack of cooperation from the parent, small oral cavity, and undercuts of the defects.

    SINGLE-VISIT FEEDING PLATE REHABILITATION IN AN 8-DAY-OLD INFANT WITH UNILATERAL CLEFT LIP AND PALATE: A CASE REPORT · 2026 · DOI

  • There is a need to understand the frequency of risk factors associated with orofacial malformations and neural tube defects. There is a lack of studies on the prevalence of these malformations in specific populations.

    Factores de riesgo ambientales asociados a malformaciones orofaciales y defectos del tubo neural en recién nacidos · 2026 · DOI

  • Future research should focus on longitudinal studies to assess the progression of middle ear dysfunction in children with cleft palate and evaluate the long-term outcomes of various interventions. Longitudinal studies are warranted to monitor changes over time.

    PREVALENCE OF MIDDLE EAR DYSFUNCTION IN CHILDREN WITH CLEFT PALATE IN LAGOS, NIGERIA · 2026 · DOI

  • Within the limitations of the present study: The TMJ structures of healthy individuals and patients with UCLP were not exactly the same.

    Temporomandibular joint morphology in patients with unilateral cleft lip and palate · 2026 · DOI

  • Although the issue has not been clarified in a recent systematic review,17 the inclination of the AE might be a predisposing factor for disc displacement with reduction of TMJ.

    Temporomandibular joint morphology in patients with unilateral cleft lip and palate · 2026 · DOI

  • The current evidence on the effect of postoperative feeding methods in infants with cleft lip and palate is uncertain. There is a need for well-designed clinical trials to determine the true effect of these methods.

    Effect of postoperative feeding methods in patients with cleft lip and palate: A systematic review and meta-analysis · 2026 · DOI

  • Understanding the etiology of NSOC is a challenge requiring a multidisciplinary approach. The exact number of genes related to the etiology of NSOC is currently impossible to determine.

    Relation of the WNT5A gene and non-syndromic orofacial clefts · 2026 · DOI

  • Methionine Synthase (MTR) rs1805087 A2756G and Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase, and Formyltetrahydrofolate Synthetase 1 (MTHFD1) rs2236225 G1958A are two genes suspected of being risk factors for NS CLP and NS CP, but they have not been studied in the Indonesian population.

    Analysis of MTR rs1805087 A2756G in non-syndromic cleft lip and palate and MTHFD1 rs2236225 G1958A in non-syndromic cleft palate among Indonesian Deutero-Malay population · 2026 · DOI

  • To investigate the genetic and environmental risk factors. To develop more effective treatment approaches. To improve outcomes for children with cleft lip and/or palate.

    Cleft Lip and/or Palate: A Comprehensive Review and our Treatment Approach · 2026 · DOI

  • Limited treatment options for adolescents with cleft palate.

    Maxillary protraction effectiveness in adolescents with cleft palate: A systematic review and network meta-analysis · 2026 · DOI

  • Retrospective study, - Limited to two-dimensional assessment, - No quantitative information on baseline cleft severity, - Small sample size of 48…

    Covariation Between Palatal Shape and Craniofacial Morphology in Complete Unilateral Cleft Lip, Alveolus, and Palate: A Geometric Morphometric Study · 2026 · DOI

  • Further longitudinal studies using fully three-dimensional assessment, - Investigation of palate–craniofacial relationships in larger samples, - Examination of the effects of different treatment protocols on palatal and craniofacial…

    Covariation Between Palatal Shape and Craniofacial Morphology in Complete Unilateral Cleft Lip, Alveolus, and Palate: A Geometric Morphometric Study · 2026 · DOI

  • Further investigation of the 309 high-order interactor genes not previously associated with OFC. Exploration of the potential therapeutic applications of the identified genetic drivers.

    Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease · 2026 · DOI

  • Se requieren ensayos clínicos bien diseñados y con tamaños muestrales adecuados, - Es necesario considerar otros factores que podrían influir en los resultados, - Deben realizarse más estudios para determinar el verdadero efecto de los métodos de alimentación…

    Effect of postoperative feeding methods in patients with cleft lip and palate: A systematic review and meta-analysis · 2026 · DOI

Most-cited papers in Cleft Lip and Palate Research

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Open questions raised by papers listed on this page include: (1) There is a need to evaluate the effectiveness of NAM therapy in improving feeding outcomes in CLP patients (“Nasoalveolar Molding and Feeding in Infants with Cleft Lip and Palate: An…”, 2026); (2) Given their large size, they can have an outsized effect on phenotype, however, the contribution of SVs to the genetic architecture of orofacial clefts (OFCs) is not well understood (“Characterization of de novo structural variants in trios with orofacial clefts”, 2026); (3) The case demonstrates BFP flap success in very advanced age with geriatric constraints such as frailty and limited anesthetic tolerance, but broader clinical evidence from comparative studies across elderly populations is needed (“Reconstruction of a partial maxillectomy defect using a pedicled buccal fat pad…”, 2026); (4) The complex interactions between various cellular and molecular events in palatogenesis are not fully understood (“Multiscale Convergence of Signaling, Epigenetic, and Environmental Networks in…”, 2026); (5) The genetic etiology of OFC subtypes is not well understood (“Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios…”, 2026). 343 gap statements have been mined from Cleft Lip and Palate Research papers in our 7.9M-paper local library, which holds 3,232 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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