Vermeij-Keers, C.

A systematic review of associated structural and chromosomal defects in oral clefts: When is prenatal genetic analysis indicated? (Article)

2012-08-01T00:00:00Z

Background: Oral clefts-comprising cleft lip (CL), cleft lip with cleft palate (CLP), and cleft palate (CP)-are being diagnosed prenatally more frequently. Consequently, the need for accurate information on the risk of associated anomalies and chromosomal defects to aid in prenatal counselling is rising. This systematic review was conducted to investigate the prenatal and postnatal prevalence of associated anomalies and chromosomal defects related to cleft category, thereby providing a basis for prenatal counselling and prenatal invasive diagnostics. Methods: Online databases were searched for prenatal and postnatal studies on associated anomalies and chromosomal defects in clefts. Data from the literature were complemented with national validated data from the Dutch Oral Cleft Registry. Results: Twenty studies were included: three providing prenatal data, 13 providing postnatal data, and four providing both. Data from prenatal and postnatal studies showed that the prevalence of associated anomalies was lowest in CL (0-20.0% and 7.6-41.4%, respectively). For CLP, higher frequencies were found both prenatally (39.1-66.0%) and postnatally (21.1-61.2%). Although CP was barely detectable by ultrasound, it was the category most frequently associated with accompanying defects in postnatal studies (22.2-78.3%). Chromosomal abnormalities were most frequently seen in association with additional anomalies. In the absence of associated anomalies, chromosomal defects were found prenatally in CLP (3.9%) and postnatally in CL (1.8%, 22q11.2 deletions only), CLP (1.0%) and CP (1.6%). Conclusions: Prenatal counselling regarding prognosis and risk of chromosomal defects should be tailored to cleft category, and more importantly to the presence/ absence of associated anomalies. Irrespective of cleft category, clinicians should advise invasive genetic testing if associated anomalies are seen prenatally. In the absence of associated anomalies, prenatal conventional karyotyping is not recommended in CL, although array comparative genomic hybridisation should be considered. In presumed isolated CLP or CP, prenatal invasive testing, preferably by array based methods, is recommended.

Decreasing prevalence of oral cleft live births in the Netherlands, 1997-2006 (Article)

2011-05-01T00:00:00Z

Objectives: The number of new oral cleft patients has fallen in the Netherlands. This may be explained by two hypotheses: (1) greater prenatal detection of congenital anomalies has led to more pregnancy terminations and (2) increased folic acid use has reduced the oral cleft risk. Both hypotheses would mainly apply to the category cleft lip/alveolus ± cleft palate (CL±P), since, unlike cleft palate only (CP), CL±P can be detected prenatally by two-dimensional (2D) ultrasound and develops during the period recommended for folic acid use. The authors aimed to determine trends in prevalence over 1997-2006 and to evaluate the hypotheses by stratifying trends by cleft category. Methods: This study was a time-trend analysis of infants born alive with oral clefts in the Netherlands during 1997-2006 and registered in the national oral cleft registry. The authors calculated prevalence rates and the estimated annual percentage change (EAPC) for all oral clefts and the two categories. Results: In 1997-2006, 3308 infants out of 1 970 872 live births had oral clefts, an overall prevalence per 10 000 live births of 16.8 (CL±P: 11.3; CP: 5.5). Time-trend analysis showed that the prevalence of all oral clefts decreased (EAPC -1.8%; 95% CI: -3.0% to -0.6%), as did the CL±P prevalence (EAPC -2.3%; 95% CI: -3.8% to -0.9%). No significant trends were found for the CP prevalence. Conclusions: Because the live-birth prevalence of CL±P decreased, that of all oral clefts decreased. These findings are in line with both hypotheses and may therefore have implications for prenatal counselling and folic acid policy.

Ten years recording common oral clefts with a new descriptive system (Article)

2011-03-01T00:00:00Z

Objective: After introducing a new descriptive recording system for congenital craniofacial abnormalities in The Netherlands, common oral clefts are highlighted. Design: Prospective observational study. Setting: Fifteen cleft palate teams, united in the Dutch Association for Cleft Palate and Craniofacial Anomalies, registered patients from 1997 to 2006. Patients: All unoperated patients with a common oral cleft were included. Main Outcome Measures: Detailed information and birth prevalence rates of cleft lip/alveolus, cleft lip/alveolus and palate, and cleft palate were provided, relating referral age, gender, family history, additional congenital abnormalities, and syndrome diagnoses to these three categories. Results: This study included 3512 patients, resulting in an overall prevalence of 16.6 per 10,000 live births. Patients showed a cleft lip/alveolus (28%), a cleft lip/alveolus and palate (39%), or a cleft palate (33%).The three categories exhibited very heterogeneous cleft types.Mean referral age was 5.8 months (median 3 weeks).Birth weight was the lowest in cleft palate patients (3238 g; p < .001 to .009). Cleft palate patients showed less positive family history concerning congenital anomalies (23%, p < .001 to .013), but more syndrome diagnoses were established in this category (24%, p < .001). Ten percent of all cleft patients showed additional abnormalities of the head and neck area, and 13% displayed congenital anomalies of other systems. Conclusions: This new recording method allows adequate description of common oral clefts.Many cleft types exist within these three categories and should be differentiated, because they originate from different time frames and/or cell biological mechanisms during embryogenesis.

Validation of the NVSCA registry for common oral clefts: Study design and first results (Article)

2010-09-01T00:00:00Z

Objective: Since 1997 the Dutch Association for Cleft Palate and Craniofacial Anomalies (NVSCA) has maintained a national registry of congenital craniofacial anomalies. This study validates data on three common oral cleft categories (cleft lip/alveolus = CL/A; cleft lip/alveolus and palate = CL/AP; and cleft palate = CP) and general items. Design: Retrospective observational study. Setting: All 15 Dutch cleft palate teams registered presurgery patients with common oral clefts (n = 2553) from 1997 to 2003. Patients: A random sample of 250 cases was used; 13 cases were excluded. Main Outcome Measures: The corresponding medical data were reviewed; these medical data served to validate the NVSCA registry data. Prevalence comparisons, 2 X 2 tables and validity measures were performed. Results: The cleft categories most accurately recorded were CL/A and CP. Both categories had an observed agreement of 98%, kappa of 0.94, and a sensitivity and specificity of 97%. Cleft lip/alveolus and palate had an observed agreement of 95%, kappa of 0.89, a sensitivity of 90%, and a specificity of 99%. Regarding the general items, observed agreement and kappa were highest for adoption/foster child (99%; 0.76) and lowest for remarks about pregnancy (63%; 0.20). Sensitivity ranged from 25% (consanguinity) to 97% (white mother) and specificity was high for all items (>93%) except for white father and mother (approximately 35%). Conclusions: The NVSCA registry is a valuable tool for quality improvement and research because validity on all three common oral cleft categories is very good. Validity on the general items is reasonable to satisfying and appears to be related to the type of information.

The frontosphenoidal suture: Fetal development and phenotype of its synostosis (Article)

2008-04-01T00:00:00Z

Background: Isolated synostosis of the frontosphenoidal suture is very rare and difficult to diagnose. Little has been reported on the clinical presentation and fetal development of this suture. Objective: To understand the development of the frontosphenoidal suture and the outcome of its synostosis. Materials and methods: We studied the normal fetal development of the frontosphenoidal suture in dry human skulls and the clinical features of four patients with isolated synostosis of the frontosphenoidal suture. Results: The frontosphenoidal suture develops relatively late during the second trimester of pregnancy, which explains the mild phenotype when there is synostosis. This rare craniosynostosis results in a deformity that causes recession of the lateral part of the frontal bone and supraorbital rim, with minimal facial asymmetry. Three-dimensional CT is the best examination to confirm the diagnosis. Conclusion: Isolated frontosphenoidal synostosis should be considered in patients with unilateral flattening of the forehead at birth that does not improve within the first few months of life.