Predicting Syndromic Status Based on Longitudinal Data from Parental Reports of the Presence of Additional Structural and Functional Anomalies in Children Born with an Orofacial Cleft.

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.