“New” Autosomal-Dominant Infantile Sensorineural Non-Progressive High-Frequency Hearing Loss: Report on a Brazilian Family Sthella Zanchetta, 1,2 Kouzaburo Ohara, 1 Patricia T. Rodrigues, 1,2 Ester L.L. Carvalho, 2 and Antonio Richieri-Costa 1,3 * 1 Faculdade de Medicina, Universidade de Marı ´lia, Marı ´lia, Sa ˜ o Paulo, Brazil 2 Faculdade de Cie ˆncias da Sau ´ de, Universidade de Marı ´lia, Marı ´lia, Sa ˜ o Paulo, Brazil 3 Departamento de Gene ´tica Clı´nica, Hospital de Reabilitac ¸a ˜ o de Anomalias Craniofaciais, Universidade de Sa ˜o Paulo, Bauru, Sa ˜ o Paulo, Brazil We report on a three-generation Brazilian family with seven patients affected with non-progressive high-frequency sensori- neural hearing loss with no associated anomalies first noted in early infancy. To our knowledge this is the first report on this autosomal-dominant condition. Clinical, au- diological, and genetic aspects are dis- cussed. Am. J. Med. Genet. 95:13–16, 2000. © 2000 Wiley-Liss, Inc. KEY WORDS: autosomal-dominant inheri- tance; high-frequency senso- rineural hearing loss; non- progressive deafness INTRODUCTION Sensorineural hearing loss is part of the clinical pic- ture of hundreds of environmental, chromosomal, and inherited conditions [Gorlin et al., 1995]. Autosomal- recessive inheritance is the mode of transmission re- sponsible for 80% of genetic childhood deafness, whereas only 15% are due to dominant genes [Van Laer et al., 1999]. Most of the autosomal-recessive prelin- gual deafness (20%) are related with mutations in Con- exin 26 [Kimberling, 1999; Cohn and Kelley, 1999]. “Nearly all genes that have been localized for autoso- mal dominantly inherited hearing impairment are characterized by post-lingual hearing loss that is pro- gressive in nature” [Van Laer et al., 1999]. To date 22 loci have been mapped for autosomal-dominant low, mid-, and high-frequency hearing loss (DFNA1 to DFNA22 ), and excluding DFNA3, DFNA8, and DFNA12, all DNFA genes are responsible for progres- sive post-lingual deafness [Van Laer et al., 1999]. Here we report on a Brazilian family with seven affected patients in three generations with an autosomal- dominant post-lingual non-progressive high-frequency sensorineural hearing loss. To our knowledge this is the first report on this condition since up to now all mapped genes responsible for non-progressive sensori- neural deafness (DFNA3, DFNA8, and DFNA12) in- volves all frequencies and are congenital (prelingual) in nature [Van Laer et al., 1999]. CLINICAL REPORTS Patient III-5 (Fig. 1) was born in 1988 to a G2P2 healthy, 27-year-old mother and her non-consanguineous 37-year-old husband. There was information about other relatives with hearing problems. Pregnancy was normal with no exposure to toxins, infections, trau- matic incidents, or radiation. Delivery was normal at term. Birth weight, length, and OFC were not re- corded. He was first seen at age 7 years for speech problems and vague reference of hearing problems. Brainstem audiometry at this time showed hearing loss ranging from 25 to 30 db loss at 1,500 Hz to 60 to 80 db at 8,000 Hz (Fig. 2). No other anomalies were found in ear, ophthalmological, and clinical evaluation. Results of laboratory blood tests and G-banded chro- mosomes were normal. Patient III-4, the older sister of patient 1, was born in 1987. She had also speech and hearing problems that affected her academic performance. Brainstem audi- ometry showed bilateral sensorineural hearing loss similar to that of her brother (Fig. 3). Computed tomog- raphy scan was normal. Patient II-3, father of patients 1 and 2, is 47 years old. He has referred to himself as “hard of hearing” since infancy, especially in a noisy environment. Brain- stem audiometry showed bilateral sensorineural hear- ing loss to high frequencies. Patient III-6, is a 15-year-old first cousin of patients 1 and 2. He had no objective hearing difficulties, but he was referred at school as an “awareness” student. Brainstem audiometry showed bilateral sensorineural hearing loss to high frequencies. *Correspondence to: A. Richieri-Costa, Department of Clinical Genetics, HRAC-USP, Caixa Postal 620, 17043-900 Bauru, SP, Brasil. Received 20 October 1999; Accepted 11 May 2000 American Journal of Medical Genetics 95:13–16 (2000) © 2000 Wiley-Liss, Inc.