Etiological investigation of the oculoauriculofrontonasal syndrome

• Grant number: 23/15095-9
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Roseli Maria Zechi Ceide
• Grantee: Roseli Maria Zechi Ceide
• Host Institution: Hospital de Reabilitação de Anomalias Craniofaciais (HRAC). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated researchers: Cristiano Tonello ; Maria Rita dos Santos e Passos Bueno ; Nancy Mizue Kokitsu Nakata ; SIULAN VENDRAMINI PAULOVICH PITTOLI

Abstract

The oculoauriculofrontonasal syndrome (OAFNS) is an extremely rare condition, with isolated cases and unknown etiology. The OAFNS is characterized by the clinical overlap of two well-described conditions: the frontonasal dysplasia (FND) and craniofacial microsomia (CFM). Main clinical findings include ocular hypertelorism, epibulbar dermoid, broad or bifid nose, rare craniofacial clefts (mainly Tessier number 0-14, 2-12, and 7 cleft), mandibular hypoplasia, ear anomalies, preauricular tags, as well as the ectopic nasal bone, an exclusive radiological finding that reinforces the clinical diagnosis of OAFNS. Up to date, approximately 100 cases have been reported in the literature, although few is known regarding its etiology. Next generation sequencing, performed in few individuals (5 cases), were not conclusive yet, and the negative results for pathogenic variants suggested a complex, or even non-traditional, inheritance model for this condition. On the principle that increasing the number of individuals investigated by next generation sequencing could identify rare variants associated with the phenotype, and given that the HRAC/USP has a significant number of individuals with OAFNS (26 cases) under follow-up, here, we propose to carry out exome sequencing and, when possible, to associate the sequencing of affected tissue and RNA sequencing to contribute to the elucidation of the etiology of OAFNS, as well as to achieve a better understanding of abnormal craniofacial development, especially the occurrence of rare craniofacial clefts and the ectopic nasal bone. (AU)