A novel pathogenic variant in POLR1D (c.220dup, p.His74ProfsTer8) causes Treacher Collins syndrome type 2 in a Chinese patient: a case report.

introductionTreacher Collins syndrome type 2 (TCS2; OMIM# 613717) is a rare genetic disorder of craniofacial development caused by pathogenic variants in the POLR1D gene. The characteristic clinical features include downward-slanting palpebral fissures, micrognathia, hypoplastic zygomatic arches, lower eyelid coloboma, and malformations of the external and middle ears. CASE PRESENTATION: In this study, we report a 2-year-and-3-month-old male of Miao ethnicity with TCS2 caused by a novel heterozygous pathogenic POLR1D variant (NM_015972.4: c.220dup, p.His74ProfsTer8), inherited from his unaffected father. He presented with downward slanting of bilateral palpebral fissures, low-set ears, and microretrognathia, along with middle ear deformities, both confirmed by CT with 3D reconstruction, accompanied by conductive hearing loss. During the neonatal period, he exhibited severe neonatal airway compromise due to combined tongue-based obstruction and laryngomalacia, necessitating a tracheostomy. Based on the above clinical manifestations and genotype, he met the diagnosis of TCS2. The tracheostomy tube was successfully decannulated at approximately 10 months of age. His prognosis was good.

conclusionThis study expands the mutational spectrum of POLR1D-related TCS2 and underscores the vital role of multidisciplinary airway intervention in severe presentations. As an exceptionally rare disorder, this case provides crucial genotype-phenotype correlations that advance both clinical management strategies and molecular understanding of TCS2 pathogenesis.