IllnessWolfram syndrome 1 + 2; differential diagnosis

NGS+

Wolfram syndrome (WFS) spectrum represents progressive neurodegenerative diseases characterized by onset of diabetes mellitus and optic atrophy before age 16, typically associated with other endocrine abnormalities, sensorineural hearing loss, progressive neurologic abnormalities (cerebellar ataxia, peripheral neuropathy, dementia etc.). Sensorineural hearing impairment ranges from congenital deafness to milder, sometimes progressive, hearing impairment. Like WFS1 (acronym DIDMOAD), WFS2 is an AR disorder caused by pathogenic variants in CISD2. WFS2 is a continuum of clinical features (juvenile-onset diabetes mellitus, optic atrophy, high-frequency sensorineural hearing impairment, urinary tract dilatation, impaired renal function, hypogonadism, severe gastrointestinal ulcer, bleeding). The diagnostic yield for WFS is less than 100% but not precisely quantified. In addition, there are rare, dominant, severe types of WFS.

(Basic diagnostic genes: WFS1, CISD2; additional genes: -).

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK4144/

• Sympt.: Diabetes Insipidus + Diabetes mellitus + Optic Atrophy + Deafness [DIDMOAD]
• Alias: Arginine vasopressin deficiency-diabetes mellitus-optic atrophy-deafness syndrome
• Alias: Diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome
• Alias: Diabetes insipidus-diabetes mellitus-optic atrophy-hearing loss syndrome
• Allelic: Charcot-Marie-Tooth disease, XLR, 5 (PRPS1)
• Allelic: Deafness, XL 1 (PRPS1)Gout, PRPS-related (PRPS1)
• Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
• Allelic: Optic atrophy 1 (OPA1)
• Allelic: Retinitis pigmentosa 51 (TTC8)
• Alstrom syndrome (ALMS1)
• Arts syndrome (PRPS1)
• Bardet-Biedl syndrome (BBS1, -2, -4, -7, -9, -10, -12)
• Bardet-Biedl syndrome 13 (MKS1)
• Bardet-Biedl syndrome 6 (MKKS)
• Bardet-Biedl syndrome 8 (TTC8)
• Behr syndrome (OPA1)
• Cataract 41 (WFS1)
• Deafness, AD 6/14/38 (WFS1)
• Friedreich ataxia (FXN)
• Friedreich ataxia with retained reflexes (FXN)
• Joubert syndrome 28 (MKS1)
• McKusick-Kaufman syndrome (MKKS)
• Meckel syndrome 1 (MKS1)
• Mitochondrial DNA depletion syndrome 14, encephalocardiomyopathic type (OPA1)
• Mohr-Tranebjaerg syndrome (TIMM8A)
• Myotonic dystrophy 1 (DMPK)
• Optic atrophy plus syndrome (OPA1)
• Phosphoribosylpyrophosphate synthetase superactivity (PRPS1)
• Thiamine-responsive megaloblastic anemia syndrome (SLC19A2)
• Wolfram syndrome 1(WFS1)
• Wolfram syndrome 2 (CISD2)
• Wolfram-like syndrome, AD (WFS1)