Analysis of phenotypic characteristics and mutation patterns in syndromic craniofacial anomalies: Insights from a tertiary care medical genetics unit in South India

ABSTRACT Context: Craniofacial anomalies (CFAs) are rare congenital anomalies that have a profound impact on social acceptance. Most of the syndromic CFAs are genetic in origin and are the result of alteration in single or multiple genes inherited from parents or de novo . Aims: The main aim of this study was to explore the phenotypic variations and the mutation profiles in the various CFA. Subjects and Methods: This was a retrospective study where records of 20 patients were obtained from electronic medical records for analysis. The numbers provided do not accurately reflect the true prevalence as they only encompass cases referred to our department for testing. Results: The median age in this cohort was 1 year with males 60% and females 40%. Out of 20 cases, 8 cases were classified as CFA-associated craniosynostosis and 12 with orofacial clefts. Disease-causing genes identified were FGFR2, RTTN, ASXL3, IRF6, TP63, POLR1D, TCOF1, KMT2D, KDM6A, LARP1 , and C5orf42 . Most of these craniofacial syndromes were predominantly autosomal dominant, sporadic, and de novo . We had three autosomal recessive cases ( RTTN, LARP1 , and C5orf42 ) and one X-linked dominant case ( KDM6A ). Two novel variants were identified, one for Van der Woude syndrome and another for Crouzon’s syndrome. Conclusions: Although these syndromes are rare in occurrence, the present study provides a detailed phenotypic spectrum and causative mutation in various CFAs in Indian patients. This is crucial for understanding the genetic basis of these conditions and can potentially lead to advancements in diagnosis, treatment, and appropriate genetic counseling.