综合征型耳聋患者分子遗传学及临床特征分析OA

Objective To report molecular genetics and clinical characteristics in 6 patients with syndromic hearing loss,as well as their pathogenic genes and genetic features.Methods Six patients with sudden sensorineural hearing loss(SHL)who were treated in the Department of Otorhinolaryngology Head and Neck Surgery of Gaozhou People's Hospital from October 2016 to August 2025 were included.Medical history and auxiliary examination results were collected in the 6 patients,including audiology and imaging studies.Potential pathogenic gene variants were screened through whole exome sequencing(WES).Results Final diagnoses included CHARGE syndrome(n=2),Kabuki syndrome(n=1),Treacher Collins syndrome(n=1),Usher syndrome(n=1)and neurofibromatosis type 2(n=1).Except for the patient with Kabuki syndrome who had bilateral mixed hearing loss and the one with Treacher Collins syndrome who had bilateral conductive hearing loss,all other four patients had bilateral profound sensorineural hearing loss,accompanied by ear deformities including partial absence of the auricle,windward ear,microtia,external auditory canal occlusion,enlarged vestibule,underdeveloped cochlea,underdeveloped auditory nerve and underdeveloped middle ear.All 6 patients had typical multiple system malformations,including facial deformities,visual impairments,fundus lesions,eyelid abnormalities,congenital heart diseases and respiratory tract malformations.WES test detected heterozygous mutations as CHD7 c.4393C>T and CHD7 c.2499-2A>C in the 2 cases of CHARGE syndrome,KMT2D c.14216_14217 del in the case of Kabuki syndrome,TCOF1 c.4362,4366.del in the case of Treacher Collins syndrome,USH2A c.2299del in the case of Usher syndrome,and NF2 c.1031_1062del in the case of neurofibromatosis type 2.Conclusions The phenotype of syndromic hearing loss is complex and heterogeneous,and diagnosis requires a comprehensive judgment based on detailed physical examination,imaging and genetic testing.Accurate diagnosis and disease assessment are of important clinical significance in genetic counseling and subsequent surgical intervention.In our cases,the mutation sites in Treacher Collins syndrome and neurofibromatosis type 2 are detected and identified,expanding the mutation spectrum of TCOF1 and NF2.