DFNX1 Nonsyndromic Hearing Loss and Deafness – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: DFNX1 nonsyndromic hearing loss and deafness is part of the spectrum of PRPS1-related disorders. Hearing loss in hemizygous males is bilateral, sensorineural, and moderate to profound; prelingual or postlingual in onset; and progressive or non-progressive. The audiogram shape is variable. Hearing in female carriers can be normal or abnormal.

Diagnosis/testing: Diagnosis relies on the presence of characteristic hearing loss in males and detection of a hemizygous PRPS1 pathogenic variant.

Management: Treatment of manifestations: Routine management of sensorineural hearing loss. Cochlear implantation can improve auditory and oral communication skills in affected males.

Surveillance: Regular audiologic evaluation to assess hearing status and progression of hearing loss.

Evaluation of relatives at risk: Evaluate at-risk males at birth with detailed audiometry to assure early diagnosis and treatment of hearing loss.

Genetic counseling: DFNX1 is inherited in an X-linked manner. The father of an affected male will not have the disorder nor will he be a carrier of the pathogenic variant. If the mother of an affected male has a pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the variant will be affected; females who inherit the variant will be carriers and may have hearing loss. Carrier testing for at-risk female relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible if the PRPS1 pathogenic variant in the family has been identified.