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Key Points

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  • Disease summary:

    • Usher syndrome is characterized by sensorineural hearing loss and retinitis pigmentosa (RP) with or without vestibular dysfunction.

    • Pendred syndrome is characterized by nonsyndromic hearing loss with enlarged vestibular aqueducts (EVA) and/or Mondini dysplasia (incomplete partition or common cavity malformation of the inner ear) in combination with euthyroid goiter or thyroid dysfunction. DFNB4 hearing loss is characterized by the same features of Pendred syndrome without thyroid abnormalities.

  • Hereditary basis:

    • Usher syndrome is inherited in an autosomal recessive manner.

    • Pendred syndrome or DFNB4 hearing loss is inherited in an autosomal recessive manner. However, there are rare reports of possible digenic inheritance involving the FOXI1 and KCNJ10 genes.

  • Differential diagnosis:

    • Usher syndrome

      • Nonsyndromic hearing loss or nonsyndromic RP

      • Deafness-dystonia-optic neuronopathy (DDON)

      • Mitochondrial disorders

      • Diabetic neuropathy

      • Viral infections

      • Alstrom syndrome

      • Bardet-Biedl syndrome

  • Pendred syndrome

    • Branchiootorenal syndrome (BOR)

    • Brachiooto syndrome (BO)

    • Waardenburg syndrome

    • Deafness associated with the recessive form of distal renal tubular acidosis

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Table Graphic Jump Location
Table 152-1Genetic Differential Diagnosis
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Diagnostic Criteria and Clinical Characteristics

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Diagnostic Criteria

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A clinical diagnosis of Usher syndrome can be made based on the following features:

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  • Sensorineural hearing loss with typical presentations as follows

    • Congenital severe to profound for type 1

    • Congenital moderate-to-severe sloping for type 2

    • Variable age of onset and severity for type 3, often progressive

  • RP

  • Vestibular dysfunction for type 1, which may also occur in type 3

  • Family history suggestive of autosomal recessive inheritance (though many cases are singletons)

  • Absence of other physical abnormalities such as dystonia/ataxia (DDON), obesity/cardiomyopathy/insulin resistance (Alstrom syndrome), obesity/postaxial polydactyly/cognitive impairment/genital abnormalities/renal abnormalities (Bardet-Biedl syndrome), or features suggestive of a mitochondrial disorder.

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A genetic diagnosis of Usher syndrome can also be made based on the presence of two pathogenic variants in a ...

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