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Updated: Jun 6, 2025
Quantification of Orofacial Phenotypes in Xenopus
Published on: November 6, 2014
Predicting Syndromic Status Based on Longitudinal Data from Parental Reports of the Presence of Additional Structural
Amy J V Davies1, Yvonne E Wren1,2,3, Mark Hamilton4
1The Cleft Collective, University of Bristol, Bristol BS8 2BN, UK.
Insights
Children with orofacial clefts and multiple anomalies are more likely to have an undiagnosed syndrome. Prioritizing genetic screening for these children can improve diagnosis and care.
Area of Science:
- Medical Genetics
- Craniofacial Biology
- Pediatric Congenital Anomalies
Background:
- Orofacial clefts are common craniofacial birth defects, with about 30% linked to syndromes involving multiple anomalies.
- Many syndromes associated with orofacial clefts remain undiagnosed, despite indicators like co-occurring structural and functional issues.
Purpose of the Study:
- To assess how additional structural and functional anomalies aid in identifying children with undiagnosed syndromes.
- To investigate the predictive value of multiple anomalies for syndromic status in orofacial cleft patients.
Main Methods:
- Secondary data analysis of 1701 children with orofacial clefts from the UK Cleft Collective cohort (2013-2023).
- Descriptive statistics to explore anomaly and syndrome prevalence.
- Logistic regression to evaluate anomalies as predictors of syndromic status.
Main Results:
- Syndromes or sequences were identified in 20.5% of children.
- Children with five or more anomalies had an 81.5% prevalence of diagnosed syndromes.
- 27 of 32 tested anomalies significantly increased the odds of having a syndrome (p < 0.002).
Conclusions:
- Children with orofacial clefts and two or more anomalies have a significantly higher likelihood of an underlying syndrome.
- These children warrant prioritized genetic screening and counseling for timely diagnosis and management.
Abstract:
Background: Orofacial clefts are the most common craniofacial congenital malformation in humans. Approximately 30% of clefts arise as part of a syndrome or sequence, characterised by co-existing structural and functional anomalies. Many syndromes are thought to be undiagnosed, although the presence of multiple anomalies may indicate the presence of a syndrome or sequence. Aim: To determine the extent to which the presence of additional structural and functional anomalies can help to identify those children with an undiagnosed syndrome. Methods: Secondary data analysis was performed using data from 1701 children born with an orofacial cleft, collected as part of a longitudinal cohort study, the Cleft Collective. Data were collected between 2013 and 2023 across the United Kingdom. The prevalence of structural and functional anomalies and syndromes were explored using descriptive statistics. Logistic regression was used to determine the extent to which anomalies can predict syndromic status. Results: A syndrome and/or sequence was reported in 20.5% children. Among children who reported five or more anomalies, the prevalence of a diagnosed syndrome was 81.5%. When adjusting for cleft subtype and sex, in 27 out of 32 anomalies tested, strong evidence was found to suggest increased odds of having a syndrome if the specific anomaly was present compared to if the anomaly was absent (p-values ranged between 1.4 × 10-30 and 0.002). Conclusions: Children born with a cleft who present with two or more anomalies are much more likely to have a syndrome than those with fewer anomalies and should be prioritised for genetic screening and counselling.
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