1 - Serviço de Genética Médica, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
2 - Serviço de Genética Médica, Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
- Annual Meeting Sociedade Portuguesa de Genética Humana 2023 (Poster)
Treacher Collins syndrome (TCS) is a rare mandibulofacial dysostosis (MFD) caused by pathogenic variants in TCOF1 (#154500); POLR1D (#613717); POLR1C (#248390) or POLR1B (#618939) genes, involved in ribosomal RNA transcription. Clinical features include facial bones hypoplasia, external ear anomalies, hearing loss, downward palpebral fissures, and colobomas. It is associated with incomplete penetrance and variable expression, so misdiagnosis may occur. Some patients remain without a known genetic anomaly.
Objectives and Methods: Retrospective review of clinical and molecular data from 1) patients with clinical suspicion of TCS or 2) diagnosed cases of TCS, in our outpatient Genetic Department, ranging from 2004-2023.
Results:In total, we identified 11 patients. From 1), 9 cases had initial suspicion of TCS. Of these, 4 were diagnosed with TCS (TCOF1-3; POLR1D-1); 1 with Burn-McKeown Syndrome (TXNL4A); 4 remained without molecular diagnosis and did not return for follow-up. From 2), 1 patient was diagnosed due to deafness molecular investigation (POLR1D); a father with milder phenotype was identified after segregation studies (TCOF1). Common features in this case series were malar/zygomatic hypoplasia (9/11); micrognathia (9/11); retrognathia (8/11); conductive hearing loss (8/11); downward palpebral fissures (8/11); lower eyelid coloboma (7/11), partial absence of lower eyelashes (7/11); microtia (6/11); cleft palate (6/11). In patients without molecular diagnosis, all presented malar/zygomatic hypoplasia, micro-retrogathia and 3 had hearing loss. Only 1 case had reported prenatal findings. To the best of our knowledge, we identified 3 new variants: 2 frameshift and 1 splice-site in TCOF1.
Conclusions: Phenotypic findings are consistent with literature,yet common features are not exclusive to TCS. We identified 2 cases with milder characteristics, evidencing phenotypic variation associated with TCS. These findings enhance the importance of genetic diagnosis in MFD, for proper counseling and management. Timely revision of previous undiagnosed cases is advisable. We contributed to expand molecular data, adding 3 new TCOF1 variants not previously reported.
Palavras Chave: Mandibulofacial dysostosis, Treacher-Collins syndrome, phenotype