Differential Diagnosis of Hearing Loss

Primary Classification by Type

The American College of Medical Genetics and Genomics recommends that the differential diagnosis of hearing loss should be systematically organized into conductive, sensorineural, and mixed categories, with further subdivision into genetic/syndromic, acquired/environmental, and idiopathic causes based on comprehensive history, physical examination, and targeted testing 1

The American Academy of Pediatrics suggests that GJB2 (connexin 26) mutations are the most common genetic cause of congenital hearing loss in the United States and should be tested first in nonsyndromic cases 2, 5, 6
Autosomal recessive nonsyndromic hearing loss is often caused by GJB2 mutations, which account for the majority of cases, and simplex cases can still have a 25% recurrence risk 2, 7
The National Institute on Deafness and Other Communication Disorders states that autosomal dominant nonsyndromic hearing loss is caused by various loci and is often progressive 2, 8

The American College of Medical Genetics and Genomics recommends that physical examination findings suggesting syndromic hearing loss mandate syndrome-specific evaluation and genetic testing to identify life-threatening associated conditions 3, 1
Usher syndrome is characterized by retinitis pigmentosa with hearing loss, and Waardenburg syndrome is characterized by heterochromia irides, dystopia canthorum, and white forelock 6, 3, 7

The Centers for Disease Control and Prevention states that intrauterine and postnatal infections are critical acquired causes requiring specific testing in congenital hearing loss 6, 3, 4
Congenital CMV is the most common infectious cause of hearing loss, and CMV testing should be performed in simplex nonsyndromic cases 2, 5, 6, 4

The American Academy of Pediatrics recommends that a detailed three-to-four generation pedigree is essential to identify inheritance patterns and distinguish genetic from environmental causes 6, 3, 1, 7
Systematic examination for syndromic features is mandatory, as approximately 30% of genetic hearing loss is syndromic 2, 8, 1
The National Institute on Deafness and Other Communication Disorders suggests that comprehensive hearing loss gene panel testing should include genes recommended by the Hearing Loss Gene Curation Expert Panel 1