IllnessCataract, congenital; differential diagnosis

NGS +

Hereditary congenital cataract may occur in isolation (70%), together with other ocular anomalies (15%), some of them complex, or as part of a syndrome (15%) within a broad spectrum of diseases. The latter 15% of cases have systemic features, making thorough perinatal and pediatric care essential to minimize comorbidities. In some metabolic diseases, congenital cataract may be the first sign, so prompt diagnosis is important, especially when treatment options are available. Routine genetic testing is essential for the full clinical management of patients, and analysis of many genes by next generation sequencing has been shown to accelerate the timely diagnosis. Pathogenic variants in genes affect lens-specific proteins or those that regulate eye development, among other associated ocular abnormalities. In most cases of bilateral cataract (≤77%), a causative gene mutation can be identified, with autosomal dominant inheritance being most common in nearly half of cases. However, a negative result of molecular genetic testing does not exclude the ophthalmologic diagnosis.

Reference: Hum Mutat. 2021 Sep;42(9):1173-1183. doi: 10.1002/humu.24240.

• Alias: Cataract, congenital
• Allelic: Adult i phenotype without cataract (GCNT2)
• Allelic: Ayme-Gripp syndrome (MAF)
• Allelic: Branchiootic syndrome 1 (EYA1)
• Allelic: Branchiootorenal syndrome 1, +/- cataracts (EYA1)
• Allelic: Deafness, AD (WFS1)
• Allelic: Isolated paediatric cataract [panelapp] (PGRMC1)
• Allelic: Leukodystrophy, hypomyelinating, 5 (HYCC1)
• Allelic: Nance-Horan syndrome (NHS)
• Allelic: Orofacial cleft 11 (BMP4)
• Allelic: Sengers syndrome (AGK)
• Allelic: Spastic paraplegia 42, AD (SLC33A1)
• Allelic: Wolfram syndrome 1 (WFS1)
• Allelic: Wolfram-like syndrome, AD (WFS1)
• Anterior segment anomalies +/- cataract (EYA1)
• Anterior segment dysgenesis 1, multiple subtypes (PITX3)
• Anterior segment dysgenesis 2, multiple subtypes (FOXE3)
• Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Anterior segment dysgenesis 7, with sclerocornea (PXDN)
• Brain small vessel disease +/- ocular anomalies (COL4A1)
• Cataract 1, multiple types (GJA8)
• Cataract 10, multiple types (CRYBA1)
• Cataract 11, multiple types (PITX3)
• Cataract 11, syndromic, AR (PITX3)
• Cataract 12, multiple types (BFSP2)
• Cataract 13 with adult i phenotype (GCNT2)
• Cataract 14, multiple types (GJA3)
• Cataract 15, multiple types (MIP)
• Cataract 16, multiple types (CRYAB)
• Cataract 17, multiple types (CRYBB1)
• Cataract 18, AR (FYCO1)
• Cataract 19, multiple types (LIM2)
• Cataract 2, multiple types (CRYGC)
• Cataract 20, multiple types (CRYGS)
• Cataract 21, multiple types (MAF)
• Cataract 22 (CRYBB3)
• Cataract 23 (CRYBA4)
• Cataract 3, multiple types (CRYBB2)
• Cataract 30, pulverulent (VIM)
• Cataract 33, multiple types (BFSP1)
• Cataract 34, multiple types (FOXE32)
• Cataract 36 (TDRD7)
• Cataract 38, AR (AGK)
• Cataract 39, multiple types, AD (CRYGB)
• Cataract 4, multiple types (CRYGD)
• Cataract 40, XL (NHS)
• Cataract 41 (WFS1)
• Cataract 48 (DNMBP1)
• Cataract 49 (PANK4)
• Cataract 5, multiple types (HSF4)
• Cataract 6, multiple types (EPHA2)
• Cataract 9, multiple types (CRYAA)
• Cataract [MONDO:0005129, panelapp] (PGRMC1)
• Cataract with late-onset corneal dystrophy (PAX6)
• Cataract, congenital [panelapp] (CDK9)
• Cataracts [panelapp] (NECTIN3)
• Congenital cataracts, facial dysmorphism, neuropathy (CTDP1)
• Congenital cataracts, hearing loss, neurodegeneration (SLC33A1)
• Congenital muscular dystrophy overlapping Marinesco-Sjogren s. + dystroglycanopathy (INPP5K)
• Hemorrhagic destruction of the brain, subependymal calcification + cataracts (JAM3)
• Hyperferritinemia-cataract syndrome (FTL)
• Hypomyelination + congenital cataract [panelapp] (HYCC1)
• Marinesco-Sjogren syndrome (SIL1)
• Microcephaly, congenital cataract, psoriasiform dermatitis (MSMO1)
• Microphthalmia, syndromic 6 (BMP4)
• Muscular dystrophy, congenital, cataracts; intellectual disability (INPP5K)
• Myopathy, mitochondrial progressive, congenital cataract, developmental delay (GFER)