IllnessUsher syndrome type 1 + 2 + 3, differential diagnosis

NGS +

Usher syndrome, USH, is characterized by partial or complete sensorineural hearing loss and retinitis pigmentosa, whereby both neurologic components worsen over time. Loss of night vision sets in first, followed by blind spots that develop in the peripheral visual field. In some cases, the vision is further impaired by cataract. Many people with retinitis pigmentosa retain some central vision throughout their lives. USH has been clinically classified into three types, which are distinguished by the severity of hearing loss, the presence or absence of balance problems and age at onset. These types are sometimes further subdivided into subtypes based on genetic causes. Yet, because USH (and likewise some differential-diagnostically related syndromes) represent a clinical disease continuum, the three USH types are discussed here collectively. Most people with USH1 are born with severe to profound hearing loss. Worsening of visual impairment becomes evident in childhood. USH1 also causes abnormalities of the vestibular system leading to balance problems. USH2 is characterized by hearing loss from birth and progressive vision loss that begins somewhat later in adolescence or adulthood. The hearing loss associated with this form ranges from mild to severe and primarily affects the ability to hear high-frequency sounds. Unlike the other forms, USH2 is not associated with vestibular abnormalities. Patients with USH3 suffer from hearing and visual impairments that begin later in life. USH3 is usually associated with normal hearing at birth. Hearing loss typically begins in late childhood or adolescence, after language development, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. The impaired vision caused by retinitis pigmentosa also develops in late childhood or adolescence. Some affected individuals develop abnormalities of the vestibular organ.

USH can be caused by mutations in a number of different genes. Mutations in at least six genes cause USH1; mutations in MYO7A are most common, followed by mutations in the CDH23 gene. USH2 is caused by mutations in three genes; most cases of are due to pathogenic variants in the USH2A gene. Digenic USH2 is due to mutations in ADGRV1 and PDZD7. USH3 is most commonly caused by mutations in the CLRN1 gene. Virtually all types of USH are inherited in an autosomal recessive manner. The molecular genetic yield in USH is high but incomplete (~90%). Therefore, a negative DNA test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1265/

https://www.ncbi.nlm.nih.gov/books/NBK1341/

• Alias: Retinitis pigmentosa + congenital deafness
• Alias: Retinitis pigmentosa-deafness syndrome
• Allelic: Cataract 41 (WFS1)
• Allelic: Charcot-Marie-Tooth disease, XLR, 5 (PRPS1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2W (HARS1)
• Allelic: Deafness, AD (MYO7A)
• Allelic: Deafness, AR 12 (CDH23)
• Allelic: Deafness, AR 18A (USH1C)
• Allelic: Deafness, AR 2 (MYO7A)
• Allelic: Deafness, AR 31 (WHRN)
• Allelic: Deafness, AR 48 (CIB2)
• Allelic: Deafness, AR 57 (ADGRV1)
• Allelic: Diabetes mellitus, noninsulin-dependent, association with (WFS1)
• Allelic: Febrile seizures, familial, 4 (ADGRV1)
• Allelic: Gout, PRPS-related (PRPS1)
• Allelic: Macular degeneration, XL atrophic (RPGR)
• Allelic: Phosphoribosylpyrophosphate synthetase superactivity (PRPS1)
• Allelic: Pituitary adenoma 5, multiple types (CDH23)
• Allelic: Retinitis pigmentosa 39 (USH2)
• Allelic: Retinitis pigmentosa 61 (CLRN1)
• Alport syndrome 1, XL (COL4A5)
• Alstrom syndrome (ALMS1)
• Arts syndrome (PRPS1)
• Cone-rod dystrophy + hearing loss 2 (CEP250)
• Cone-rod dystrophy and hearing loss (CEP78)
• Cone-rod dystrophy, XL, 1 (RPGR)
• Deafness, AD 6/14/38 (WFS1)
• Deafness, XL 1 (PRPS1)
• Heimler syndrome 1 (PEX1)
• Mohr-Tranebjaerg syndrome (TIMM8A)
• Peroxisome biogenesis disorder 1A, Zellweger, + 1B, NALD/IRD (PEX1)
• Retinal disease in Usher syndrome type 2A, modifier of (ADGRV1)
• Retinitis pigmentosa 3 (RPGR)
• Retinitis pigmentosa, XL, + sinorespiratory infections, +/- deafness (RPGR)
• Usher syndrome, type 1B (MYO7A)
• Usher syndrome, type 1C (USH1C)
• Usher syndrome, type 1D (CDH23)
• Usher syndrome, type 1D/F Dig (CDH23/PCDH15)
• Usher syndrome, type 1F (PCDH15)
• Usher syndrome, type 1G (USH1G)
• Usher syndrome, type 1J (CIB2)
• Usher syndrome, type 2A (USH2A)
• Usher syndrome, type 2C (ADGRV1)
• Usher syndrome, type 2C (ADGRV1/PDZD7 Dig)
• Usher syndrome, type 2D (WHRN)
• Usher syndrome, type 3A (CLRN1)
• Usher syndrome, type 3B (HARS1)
• Wolfram syndrome 1 (WFS1)
• Wolfram syndrome 2 (CISD2)
• Wolfram-like syndrome, AD (WFS1)