Cleft Lip Repair and Primary and Intermediate Cleft Rhinoplasties.

The cleft lip is one of the most common craniofacial abnormalities seen worldwide. The lip and primary rhinoplasty repairs are performed together in a single surgery for patients aged 3 to 6 months. The intermediate rhinoplasty has fallen out of favor due to more advanced approaches at primary rhinoplasty. However, it still plays a role in addressing severe nasal airway obstruction or correcting anatomic differences causing emotional distress from social ridicule. The article reviews the incidence of cleft lip, discusses its development and variant anatomy, and examines the approaches to surgical repair of the cleft clip, primary and intermediate rhinoplasties.

Defining the Treatment Gap in Nasoalveolar Molding: Factors Affecting the Utilization of NAM in an Urban Cleft Center.

BACKGROUND: Many cleft centers incorporate NasoAlveolar Molding (NAM) into their presurgical treatment protocols. However, there are limited data on eligible patients who do not receive or complete NAM. This study characterizes the demographics associated with non-utilization or completion of NAM. METHODS: A single-institution retrospective review was performed of all patients with cleft lip and alveolus undergoing primary unilateral and bilateral cleft lip repair from 2012-2020. Patients were grouped based on utilization or non-utilization of NAM. Demographic and treatment data were collected, including documented reasons for not pursuing or completing NAM. RESULTS: Of 230 eligible patients, 61 patients (27%) did not undergo or complete NAM (no-NAM). In this group, 37 (60.7%) received no presurgical intervention, 12 (19.7%) received presurgical nostril retainers, 3 (4.9%) received lip taping, 1 (1.6%) received a combination of taping/nostril retainers, and 8 (13.1%) discontinued NAM. The most common reasons for not receiving NAM were sufficiently aligned cleft alveolus (21.3%), medical complexity (16.4%), late presentation (16.4%), and alveolar notching (18%). Compared to the NAM group, the no-NAM group had significantly lower rates of prenatal cleft diagnosis/consult, and significantly higher proportion of non-married and non-English speaking caregivers. Multivariable analysis controlling for insurance type, primary language, prenatal consult, marital status, and age at first appointment found that age at first appointment is the only statistically significant predictor of NAM utilization (P < .001). CONCLUSIONS: Common reasons for non-utilization of NAM include well-aligned cleft alveolus, medical complexity, and late presentation. Early presentation is an important modifiable factor affecting rates of NAM utilization.

Association between gestational exposure and risk of orofacial clefts: a systematic review and meta-analysis.

BACKGROUND: The occurrence of orofacial Clefts (OFCs) is a congenital disease caused by many factors. According to recent studies, air pollution has a strong correlation with the occurrence of OFCs. However, there are still some controversies about the current research results, and there is no relevant research to review the latest results in recent years. OBJECTIVE: In this paper, the authors conducted a systematic review and meta-analysis to explore the correlation between ambient air pollution and the occurrence of neonatal OFCs deformity. METHODS: We searched Pubmed, Web of science, and Embase databases from the establishment of the database to May 2023. We included observational studies on the relationship between prenatal exposure to fine particulate matter 2.5 (PM2.5), fine particulate matter 10 (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO) and the risk of cleft lip (CL), cleft palate (CP), cleft lip with or without palate (CL/P). the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the literature. Funnel plot and Egger's regression were used to verify the publication bias. Random effect model or fixed effect model was used to estimate the combined relative risk (RR) and 95% confidence interval (95%CI). RESULTS: A total of eleven studies were included in this study, including four cohort studies and seven case-control studies, including 22,453 cases of OFCs. Ten studies had low risk of bias and only one study had high risk of bias. Three studies reported that PM2.5 was positively correlated with CL and CP, with a combined RR and 95%CI of 1.287(1.174,1.411) and 1.267 (1.105,1.454). Two studies reported a positive correlation between O3 and CL, with a combined RR and 95%CI of 1.132(1.047,1.225). Two studies reported a positive correlation between PM10 and CL, with a combined RR and 95%CI of 1.108 (1.017,1.206). No association was found between SO2, CO, NO2 exposure during pregnancy and the risk of OFCs. CONCLUSION: The results of this study showed that there was a significant statistical correlation between exposure to PM10, PM2.5, O3 and the risk of OFCs in the second month of pregnancy. Exposure assessment, research methods and mechanisms need to be further explored.

Ultrasound measurements of fetal facial profile markers and their associations with congenital malformations during early pregnancy.

BACKGROUND: Fetal facial profile could be measured during the early pregnancy. Its abnormalities might be associated with certain congenital malformations. We aimed to study the associations between fetal facial profile measurements with crown-rump length and congenital malformations (cleft lip and palate, micrognathia, and open spina bifida) during early pregnancy. METHODS: We performed a prospective cross-sectional study between June 2019 and April 2022. Pregnant women at a gestational age between 11-13+ 6 weeks were enrolled. Two sonographers performed fetal facial profile measurements independently. The associations between these measurements with crown-rump length and congenital malformations were evaluated. RESULTS: There were 406 and 25 fetuses without or with congenital malformations, respectively. Two sonographers showed satisfactory inter- and intra-observer agreements and reproducibility. The maxillary gap was only observed in 7.6% of normal fetuses, whereas all cleft lip and palate fetuses had a maxillary gap ≥ 0.8 mm. The crown-rump length was negatively correlated with frontomaxillary facial angle, inferior facial angle, and profile line distance but positively correlated with maxilla-nasion-mandible angle, facial maxillary angle, frontal space distance, and palatine maxillary diameter. These measurements showed various significant changes with different congenital malformations. CONCLUSIONS: Measurements of fetal facial profile in early pregnancy were feasible with satisfactory reproducibility. These measurements correlated with crown-rump length and showed significant differences with certain fetal congenital malformations.

Utilization of images and three-dimensional custom-made nostril retainer fabricate for patients with cleft lip and cleft lip nose deformities at Siriraj Hospital: preliminary phase.

A prospective study utilizing image analysis to assess nostril openings in post-operative patients with cleft lip and cleft lip nose deformities. This preliminary study seeks to employ two-dimensional (2D) images to fabricate a custom-made nostril retainer. This study was performed at Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand. This study included 30 healthy volunteers and 15 patients with cleft lip and cleft lip nose deformities. The nostril opening width and height for all participants were measured, and photographs were taken. An image analysis application was used to fabricate a three-dimensional (3D) custom-made nostril retainer. The mean differences between the direct measurements of the nostril aperture and the measurements obtained through the program did not exceed 2 mm in terms of nostril height, width, or columella. Two-dimensional photographs can be used to create a custom-made, three-dimensional nostril retainer. This retainer allows post-operative patients to maintain their nares without needing to visit the hospital, thereby reducing the cost of care.

Factors affecting the relapse of maxilla and soft tissues of nose, upper lip and velopharyngeal structures after maxillary advancement in cleft patients.

The objectives of this study were to find the factors affecting the relapses after maxillary advancement in cleft patients. This retrospective study included 25 cleft patients. The serial lateral cephalograms were used for the evaluation of the maxilla and the soft tissue relapses in 1-year post-operative period. The skeletal relapse rate correlated with the amount of skeletal movement only in horizontal direction (r = 0.483, p = 0.015). The patients with significant skeletal relapse did not have different amount of soft tissue relapses when compared to the patients without significant skeletal relapse, except for the A' point. Relapses of the soft tissue parameters of the upper lip and nose were correlated with the upper incisor tip position horizontally and vertically. When comparing the patients who underwent maxillary distraction (DO) with the patients who underwent conventional orthognathic surgery (CO), the DO group had greater NLA relapse and increase of pharyngeal depth than the CO group.

[Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome]. / Ectrodactylia, ectodermalis dysplasia, ajak- és szájpadhasadék szindróma.

The ectrodactyly-ectodermal dysplasia-clefting syndrome is an extremely rare genetic disorder that is inherited as an autosomal dominant trait, but can also occur sporadically. It is characterized by the triad of ectrodactyly (absence of fingers), ectodermal dysplasia and cleft lip and palate along with variable involvement of other organs. Both the ectodermal and mesodermal tissues may be affected resulting in a spectrum of phenotypes. Early diagnosis and treatment signify a unique challenge for those involved in the clinical management, while enable counseling and preparation of parents for the tasks ahead of them. In our report, we describe the case of a patient with sporadic EEC syndrome. In addition to the presentation of the complex phenotype along with the medical interventions, we summarize the most important characteristics of the disease, the diagnostic and therapeutic possibilities as well as the clinical significance of the accurate genetic verification. Using whole exome sequencing, we identified in the 3q28 chromosomal region a pathogenic mutation within the TP63 gene previously linked to the EEC3 phenotypes. The knowledge of pathogenic mutation provides the means to prenatal diagnostics or in vitro fertilization methods that allows us to minimize the possibility of inheriting the syndrome in the patient's offspring. By presenting our case, we aim to draw attention to this rare and disabling disease that requires the high quality works of a multidisciplinary team capable of ensuring good quality of life for the patient. Orv Hetil. 2023; 164(46): 1831-1837.

The effect of speech pathology on automatic speaker verification: a large-scale study.

Navigating the challenges of data-driven speech processing, one of the primary hurdles is accessing reliable pathological speech data. While public datasets appear to offer solutions, they come with inherent risks of potential unintended exposure of patient health information via re-identification attacks. Using a comprehensive real-world pathological speech corpus, with over n[Formula: see text]3800 test subjects spanning various age groups and speech disorders, we employed a deep-learning-driven automatic speaker verification (ASV) approach. This resulted in a notable mean equal error rate (EER) of [Formula: see text], outstripping traditional benchmarks. Our comprehensive assessments demonstrate that pathological speech overall faces heightened privacy breach risks compared to healthy speech. Specifically, adults with dysphonia are at heightened re-identification risks, whereas conditions like dysarthria yield results comparable to those of healthy speakers. Crucially, speech intelligibility does not influence the ASV system's performance metrics. In pediatric cases, particularly those with cleft lip and palate, the recording environment plays a decisive role in re-identification. Merging data across pathological types led to a marked EER decrease, suggesting the potential benefits of pathological diversity in ASV, accompanied by a logarithmic boost in ASV effectiveness. In essence, this research sheds light on the dynamics between pathological speech and speaker verification, emphasizing its crucial role in safeguarding patient confidentiality in our increasingly digitized healthcare era.

[Analysis of a Chinese pedigree affected with van der Woude syndrome due to variant of IRF6 gene].

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree affected with van der Woude syndrome (VWS). METHODS: A proband who had visited the Drum Tower Hospital Affiliated to Nanjing University Medical School in May 2020 for "two previous pregnancies with cleft lip and palate" was selected as the study subject. Trio-whole exome sequencing (trio-WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of her pedigree members (8 individuals from four generations) and bioinformatic analysis. Chromosomal microarray analysis (CMA) was used to rule out copy number variations in the fetuses. RESULTS: Trio-WES revealed that the proband and her father had both harbored a heterozygous c.742G>T (p.G248C) missense variant of the IRF6 gene, for which her mother was of the wild type. The variant was located in a region with important functions and has not been reported previously. Prediction with several software suggested that it is likely to have a significant impact on the protein structure/function and is highly correlated with the specific phenotypes in this pedigree. Sanger sequencing confirmed co-segregation of the genotypes and phenotypes in the pedigree. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was rated as likely pathogenic (PM1+PM2_Supporting+PP1+PP3+PP4). Based on the above results, pre-implantation genetic diagnosis was carried out for the proband, which has led to birth of a healthy offspring with normal results for both site testing and CMA. CONCLUSION: The IRF6: c.742G>T (p.G248C) heterozygous variant probably underlay the VWS in this pedigree. Above finding has also enabled reproductive guidance for the proband.

Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.

This study aims to identify potential variants in the TP63-IRF6 pathway and GREM1 for the etiology of non-syndromic orofacial cleft (NSOFC) among the Vietnamese population. By collecting 527 case-parent trios and 527 control samples, we conducted a stratified analysis based on different NSOFC phenotypes, using allelic, dominant, recessive and over-dominant models for case-control analyses, and family-based association tests for case-parent trios. Haplotype and linkage disequilibrium analyses were also conducted. IRF6 rs2235375 showed a significant association with an increased risk for non-syndromic cleft lip and palate (NSCLP) and cleft lip with or without cleft palate (NSCL/P) in the G allele, with pallele values of 0.0018 and 0.0003, respectively. Due to the recessive model (p = 0.0011) for the NSCL/P group, the reduced frequency of the GG genotype of rs2235375 was associated with a protective effect against NSCL/P. Additionally, offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL/P compared to the C allele holders. IRF6 rs846810 and a G-G haplotype at rs2235375-rs846810 of IRF6 impacted NSCL/P, with p-values of 0.0015 and 0.0003, respectively. In conclusion, our study provided additional evidence for the association of IRF6 rs2235375 with NSCLP and NSCL/P. We also identified IRF6 rs846810 as a novel marker associated with NSCL/P, and haplotypes G-G and C-A at rs2235375-rs846810 of IRF6 associated with NSOFC.

A comparison of maxillofacial growth in Chinese children with isolated cleft palate treated with two different palatoplasty techniques without relaxing incisions: a preliminary study.

OBJECTIVE: To assess the maxillofacial growth of patients with isolated cleft palate following the Sommerlad-Furlow modified technique and compare it with the effect of the Sommerlad technique. STUDY DESIGN: A Retrospective Cohort Study. METHODS: A total of 90 participants, 60 patients with non-syndromic isolated soft and hard cleft palate (ISHCP) underwent primary palatoplasty without relaxing incision (30 patients received the Sommerlad-Furlow modified (S-F) technique and 30 received Sommerlad (S) technique). While the other 30 were healthy noncleft participants with skeletal class I pattern (C group). All participants had lateral cephalometric radiographs at least 5 years old age. All the study variables were measured by using stable landmarks, including 11 linear and 9 angular variants. RESULTS: The means age at collection of cephalograms were 6.03 ± 0.80 (5-7 yrs) in the S group, 5.96 ± 0.76 (5-7 yrs) in the S-F group, and 5.91 ± 0.87 (5-7 yrs) in the C group. Regarding cranial base, the results showed that there were no statistically significant differences between the three groups in S-N and S-N-Ba. The S group had a significantly shortest S-Ba than the S-F & C groups (P = 0.01), but there was no statistically significant difference between S-F and C groups (P = 0.80). Regarding skeletal maxillary growth, the S group had significantly shorter Co-A, S- PM and significantly less SNA angle than the C group (P = < 0.01). While there was no significant difference between S-F & C groups (P = 0.42). The S group had significantly more MP-SN inclination than the C group (P = < 0.01). Regarding skeletal mandibular growth, there were no statistically significant differences in all linear and angular mandibular measurements between the three groups, except Co-Gn of the S group had a significantly shorter length than the C group (P = 0.05). Regarding intermaxillary relation, the S-F group had no significant differences in Co-Gn-Co-A and ANB as compared with the C group. The S group had significantly less ANB angle than S-F & C groups (P = 0.01 & P = < 0.01). In addition, there were no significant differences in all angular occlusal measurements between the three groups. CONCLUSION: As a preliminary report, Sommerlad-Furlow modified technique showed that maxillary positioning in the face tended to be better, and the intermaxillary relationship was more satisfactory than that in Sommerlad technique when compared them in healthy noncleft participants.

A neonatal case report of branchiooculofacial syndrome caused by a novel mutation in the TFAP2A gene and literature review.

RATIONALE: Branchiooculofacial syndrome (BOFS) is a rare autosomal dominant disorder with a diverse clinical phenotype. To summarise the clinical characteristics and genetic variations of neonatal-onset BOFS through a case study and literature review. PATIENT CONCERNS: A preterm neonate with a very low birth weight, born at a gestational age of 29+3 weeks, exhibited cosmetic abnormalities at a postmenstrual age of 34+6 weeks, including microcleft lip, high arched palate, curved upper lip, low ear position, and ocular hypertelorism. Hence, a genetic test on peripheral blood was carried out. DIAGNOSES: The genetic testing showed a heterozygous variant of c.724G > A (p.Glu242Lys) in the exon 4 region of the TFAP2A (transcription factor AP-2-α) gene in the short arm of chromosome 6. BOFS was confirmed based on clinical appearance and the genetic result. INTERVENTIONS: The patient underwent solely cleft lip repair at the age of 6 months with no further intervention. OUTCOMES: The infant shows normal growth and development at 1 year of age and subsequent follow-up. LESSONS: The characteristic facial features, branchial skin defects, and ocular anomalies are the main clinical manifestations of BOFS with neonatal onset, but the diverse clinical phenotype and variable genetic variants pose certain challenges for clinical diagnosis.

Role of lncRNAs and circRNAs in Orofacial Clefts.

Different modes of gene regulation, such as histone modification, transcription factor binding, DNA methylation, and microRNA (miRNA) expression, are critical for the spatiotemporal expression of genes in developing orofacial tissues. Aberrant regulation in any of these modes may contribute to orofacial defects. Noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs), have been shown to alter miRNA expression, and are thus emerging as novel contributors to gene regulation. Some of these appear to function as 'miRNA sponges', thereby diminishing the availability of these miRNAs to inhibit the expression of target genes. Such ncRNAs are also termed competitive endogenous RNAs (ceRNAs). Here, we examine emerging data that shed light on how lncRNAs and circRNAs may alter miRNA regulation, thus affecting orofacial development and potentially contributing to orofacial clefting.

[Caries in cleft patients: aetiology, prevalence, prevention, and treatment]. / Cariës bij schisispatiënten: oorzaak, prevalentie, preventie en behandeling.

The caries prevalence in patients with cleft lip and/or palate is higher in both the deciduous and permanent dentition, compared to non-cleft patients. Inadequate oral hygiene is one of the main causes. Additional, individualized advice concerning diet and oral hygiene, such as the additional advice of the Ivoren Kruis (Dutch association of dental hygienists), is of great importance. During curative treatment, attention should be paid to any dental anxiety and possible reduced compliance.

Advances in Cleft Lip and Palate Surgery.

Cleft lip with or without cleft palate is one of the most common congenital malformations, with an average prevalence of 1 in 1000 live births. Cleft lip and/or palate is incredibly phenotypically diverse, with constant advancements and refinements in how we care for patients. This article presents an in-depth review of the latest advances and current evidence in cleft lip and palate surgery. This includes presurgical infant orthopedics, perioperative practice patterns including use of enhanced recovery after surgery (ERAS) protocols, patient-reported outcome measures, and the latest adjuncts in cheiloplasty and palatoplasty.

Influence of presurgical nasoalveolar molding (PNAM) treatment in maxillary dental arch width and nasolabial symmetry in patients with unilateral complete cleft lip and palate.

Unilateral complete cleft lip and palate (UCCLP) is one of the most severe clinical subphenotypes among nonsyndromic cleft lip and/or palate (NSCL/P), that complicates surgical repair operations. Presurgical nasoalveolar molding (PNAM) is a technique used to reshape the nose, lip and alveolar bone of infants with UCCLP before surgery (the modified Mohler rotation advancement cheiloplasty and two flap palatoplasty), with the potential to facilitate surgical repair. However, the effectiveness of PNAM treatment is still a matter of debate. In this paper, the 3Shape scanning system and 3dMD stereophotography were used to assess the short-term and long-term effects of PNAM treatment on the dental arch morphology and nasolabial features of patients with UCCLP, respectively. The findings indicated that PNAM treatment negatively affects both short-term and long-term dental arch shape compared to the treatment without PNAM, particularly in terms of limiting the transverse width of the maxillary canine-to-midline. Regarding the nasal and labial symmetry, PNAM improves the symmetry of the nasal alae in patients over 7 years old and the symmetry of the lip in patients under 7 years old. Moreover, UCCLP patients who received PNAM treatment exhibited a shorter and wider shape of the nostril on the cleft side compared to those without PNAM treatment. In clinical practice, the multidisciplinary team should carefully consider the advantages and disadvantages of the outcomes of PNAM treatment when treating infants with cleft lip and palate.

Identification of copy neutral loss of heterozygosity on chromosomes 1p, 1q, and 6p among nonsyndromic cleft lip and/or without cleft palate with hypodontia.

BACKGROUND: Nonsyndromic cleft lip and/or without cleft palate (NSCL/P) with or without hypodontia is a common developmental aberration in humans and animals. This study aimed to identify the loss of heterozygosity (LOH) involved in hypodontia and NSCL/P pathogenesis. METHODS: This is a cross-sectional study that conducted genome-wide copy number analysis using CytoScan 750K array on salivary samples from Malay subjects with NSCL/P with or without hypodontia aged 7-13 years. To confirm the significant results, simple logistic regression was employed to conduct statistical data analysis using SPSS software. RESULTS: The results indicated the most common recurrent copy neutral LOH (cnLOH) observed at 1p33-1p32.3, 1q32.2-1q42.13 and 6p12.1-6p11.1 loci in 8 (13%), 4 (7%), and 3 (5%) of the NSCL/P subjects, respectively. The cnLOHs at 1p33-1p32.3 (D1S197), 1q32.2-1q42.13 (D1S160), and 6p12.1-6p11.1 (D1S1661) were identified observed in NSCL/P and noncleft children using microsatellite analysis markers as a validation analysis. The regions affected by the cnLOHs at 1p33-1p32.3, 1q32.2-1q42.13, and 6p12.1-6p11.1 loci contained selected genes, namely FAF1, WNT3A and BMP5, respectively. There was a significant association between the D1S197 (1p33-32.3) markers containing the FAF1 gene among NSCL/P subjects with or without hypodontia compared with the noncleft subjects (p-value = 0.023). CONCLUSION: The results supported the finding that the genetic aberration on 1p33-32.3 significantly contributed to the development of NSCL/P with or without hypodontia. These results have an exciting prospect in the promising field of individualized preventive oral health care.

Alarm Signals to Postpone Feeding Plate Fabrication and Nasoalveolar Molding.

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Lessons Learned from a Single Institution's Eight Years of Experience with Early Cleft Lip Repair.

Background and Objectives: The traditional approach in managing wide cleft lip deformities involves presurgical nasoalveolar molding (NAM) therapy followed by surgical cleft lip repair between three and six months of age. This institution has implemented an early cleft lip repair (ECLR) protocol where infants undergo primary cleft lip repair between two and five weeks of age without NAM. This study aims to present this institution's ECLR repair protocol over the past eight years from 188 consecutive patients with unilateral or bilateral CL/P deformity. Materials and Methods: Retrospective review was conducted at Children's Hospital Los Angeles evaluating patients who underwent ECLR before three months of age and were classified as American Society of Anesthesiologists (ASA) class I or II from 2015-2022. Anthropometric analysis was performed, and pre- and postoperative photographs were evaluated to assess nasal and lip symmetry. Results: The average age at cleft lip repair after correcting for gestational age was 1.0 ± 0.5 months. Mean operative and anesthetic times were 120.3 ± 33.0 min and 189.4 ± 35.4, respectively. Only 2.1% (4/188) of patients had postoperative complications. Lip revision rates were 11.4% (20/175) and 15.4% (2/13) for unilateral and bilateral repairs, respectively, most of which were minor in severity (16/22, 72.7%). Postoperative anthropometric measurements demonstrated significant improvements in nasal and lip symmetry (p < 0.001). Conclusions: This analysis demonstrates the safety and efficacy of ECLR in correcting all unilateral cleft lip and nasal deformities of patients who were ASA classes I or II. At this institution, ECLR has minimized the need for NAM, which is now reserved for patients with bilateral cleft lip, late presentation, or comorbidities that preclude them from early repair. ECLR serves as a valuable option for patients with a wide range of cleft severity while reducing the burden of care.

Pregnancy with Facial Cleft: 20 Years of Experience at a Single Center.

BACKGROUND: Fetal facial clefts are among the most common congenital anomalies detected prenatally. This finding may lead to termination of pregnancy in some cases. OBJECTIVES: To compare a cohort of fetuses with facial clefts in which the pregnancy was terminated to the cohort of cases that were born with facial clefts. To investigate risk factors for facial clefts. METHODS: We conducted a retrospective chart review of all women with prenatal and postnatal diagnosis of facial cleft that were managed in our institute. A telephone questionnaire was conducted regarding a positive family history and/or genetic predisposition for facial clefts abnormalities. RESULTS: The final cohort consisted of two group. One group included 54 cases of termination of pregnancy (TOP) that were performed due to cleft lip (CL) or cleft palate (CLP); 27 women answered the telephone questionnaire. The second group comprised 99 women who delivered children with facial cleft during the same period; 60 answered the questionnaire. Only seven cases were diagnosed prenatal. Among the two groups, no correlation to family history was discovered. Of note, there was one case of three consecutive fetuses with CL in one woman, without any significant genetic findings. CONCLUSIONS: To the best of our knowledge, this is the first study to describe an anatomical malformation posing an ethical dilemma before TOP. Primary prevention with folic acid and early sonographic detection of CL/CLP with multidisciplinary consultation should be considered.