Medicine:Syndromic microphthalmia
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Short description: Developmental disorder involving the eye
| Syndromic microphthalmia | |
|---|---|
| Symptoms | Abnormally small eyeball(s) |
| Usual onset | Birth[1] |
| Duration | Lifelong[1] |
| Causes | Genetic or environmental factors[1] |
| Frequency | 1 in 10,000 individuals[1] |
Syndromic microphthalmia is a class of rare congenital anomalies characterized by microphthalmia with other non-ocular malformations.[2] Syndromic microphthalmia accounts for 60 to 80% of all cases of microphthalmia.[2] Syndromic microphthalmias are caused by mutations in genes related to embryonic craniofacial development, and they are typically classified by their genetic cause.
Classification
If microphthalmia is present, genetic testing can be done to inform a specific diagnosis of a named syndrome. Twenty to forty percent of anophthalmia and microphthalmia patients are diagnosed with a recognized syndrome.[2] There are 14 numbered syndromic microphthalmies (MCOPS) primarily defined by their ocular manifestations:
| Type | Causative gene/locus | Inheritance [lower-alpha 1] | Synonyms |
|---|---|---|---|
| MCOPS1 | NAA10[3] | XL | Lenz microphthalmia syndrome |
| MCOPS2 | BCOR[4] | XLR | |
| XLD | oculofaciocardiodental syndrome | ||
| MCOPS3 | SOX2[2] | AD | SOX2 anophthalmia syndrome, anophthalmia/microphthalmia-esophageal atresia (AEG) syndrome |
| MCOPS4 | Xq27-q28[2] | XLR | microphthalmia-ankyloblepharon-intellectual disability syndrome |
| MCOPS5 | OTX2[2] | AD | OTX2-related eye disorders |
| MCOPS6 | BMP4[5] | AD | Bakrania-Ragge syndrome, microphthalmia with brain and digit anomalies |
| MCOPS7 | HCCS, COX7B, NDUFB11[2][6] | XLD | MIDAS syndrome, microphthalmia with linear skin defects (MLS) syndrome |
| MCOPS8 | SNX3[7] | AD | microcephaly-microphthalmia ectrodactyly of lower limbs and prognathism (MMEP) syndrome, Viljoen–Smart syndrome |
| MCOPS9 | STRA6[8] | AR | anophthalmia/microphthalmia and pulmonary hypoplasia, Spear syndrome, Matthew–Wood syndrome |
| MCOPS10 | unknown[2] | microphthalmia and brain atrophy (MOBA) syndrome | |
| MCOPS11 | VAX1[2] | AR | N/A |
| MCOPS12 | RARB[2] | AD, AR | microphthalmia with or without pulmonary hypoplasia, diaphragmatic hernia, and/or cardiac defects |
| MCOPS13 | HMGB3[2] | XL | colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation, Maine microphthalmos |
| MCOPS14 | MAB21L2[2] | AD, AR | colobomatous microphthalmia-rhizomelic dysplasia syndrome, microphthalmia-coloboma-rhizomelic skeletal dysplasia |
In addition to MCOPS1–14, there are many genetic syndromes of which microphthalmia is a key feature:[2]
| Causative gene/locus | Inheritance [lower-alpha 1] | Name/synonyms |
|---|---|---|
| unknown | XLD | Aicardi syndrome (AIC), agenesis of corpus callosum with chorioretinal abnormality |
| KIAA1109 | AR | Alkuraya–Kucinskas syndrome (ALKKCUS) |
| MAF | AD | Aymé–Gripp syndrome (AYGRP) |
| ACTB | AD | Fryns-Aftimos syndrome, Baraitser–Winter syndrome 1 (BRWS1) |
| ACTG1 | AD | Baraitser–Winter syndrome 2 (BRWS2) |
| unknown | Biemond syndrome | |
| FOXL2 | AD | Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) |
| SMCHD1 | AD | Bosma arhinia microphthalmia syndrome (BAMS) |
| TFAP2A | AD | Branchio-oculo-facial syndrome (BOFS), hemangiomatous branchial clefts-lip pseudocleft syndrome |
| ERCC6 | AR | Cockayne syndrome type B (CSB), cerebro-oculo-facio-skeletal syndrome 1 (COFS1) |
| CHD7 | AD | CHARGE syndrome |
| HDAC6 | XLD | Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia |
| unknown | Colobomatous microphthalmia-obesity-hypogenitalism-intellectual disability syndrome | |
| YAP1 | AD | Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or intellectual disability (COB1) |
| FAT1 | AR | Colobomatous microphthalmia, ptosis, nephropathy, and syndactyly |
| MITF | AD | Waardenburg syndrome type 2 |
| AR | COMMAD syndrome | |
| SRD5A3 | AR | Congenital disorder of glycosylation type 1q (CDG1q) |
| SMO | unknown | Curry–Jones syndrome (CJS) |
| SALL4 | AR | Duane-radial ray syndrome, Okihiro syndrome |
| FANCA, FANCD2, FANCE, FANCI, FANCL | AR | Fanconi anemia complementation groups A, D2, E, I, L |
| PORCN | XLD | Focal dermal hypoplasia, Goltz-Gorlin syndrome |
| FRAS1 | AR | Fraser syndrome 1 |
| FREM2 | AR | Fraser syndrome 2 |
| GRIP1 | AR | Fraser syndrome 3 |
| ALX3 | AR | Frontonasal dysplasia 1 (FND1) |
| ALX1 | AR | Frontonasal dysplasia 3 (FND3) |
| unknown | AR | Fryns syndrome |
| unknown | GOMBO syndrome (growth retardation, ocular abnormalities, microcephaly, brachydactyly, and oligophrenia) | |
| SLC25A24 | AD | Gorlin–Chaudhry–Moss syndrome |
| FAM111A | AD | Gracile bone dysplasia (GCLEB), Kenny-Caffey syndrome |
| unknown | Hallermann–Streiff syndrome | |
| SMG9 | AR | Heart and brain malformation syndrome (HBMS) |
| 14q32 | AD | Hemifacial microsomia |
| SIX3, SHH, PTCH1, GLI2 | AD | Holoprosencephaly types 1, 2, 3, 7, 9 |
| IKBKG | XLD | Incontinentia pigmenti |
| PDE6D | AR | Joubert syndrome 22 |
| unknown | AR | Kapur–Toriello syndrome |
| KMT2D | AD | Kabuki syndrome |
| KDM6A | XLD | |
| GDF6 | AD | Klippel–Feil syndrome types 1, 3 |
| GDF3 | XLD | |
| unknown | XLD | Macrosomia with lethal microphthalmia |
| FREM1 | AR | Manitoba oculotrichoanal syndrome (MOTA) |
| MKS1, TMEM216, TMEM67, CEP290, RPGRIP1L | AR | Meckel–Gruber syndrome types 1-5 |
| unknown | likely AD | MOMO syndrome |
| ZEB2 | AR | Mowat–Wilson syndrome |
| POMT1 | AD | Muscle–eye–brain disease type A 1-11 |
| POMT2, POMGNT1, FKTN, FKRP, CRPPA, POMGNT2, DAG1, RXYLT1, B3GALNT2 | AR | |
| NHS | XLD | Nance–Horan syndrome |
| RERE | AD | Neurodevelopment disorder with anomalies of the brain, eye, and/or heart (NEDBEH) |
| NPD | XLR | Norrie disease |
| HMX1 | AR | Oculoauricular syndrome |
| GJA1 | AD, AR | Oculodentodigital dysplasia (ODD) |
| CPLANE1 | AR | Orofaciodigital syndrome type VI |
| LRP5 | AR | Osteoporosis-pseudoglioma syndrome |
| PAX2 | AD | Papillorenal syndrome |
| ATOH7 | AR | Persistent fetal vasculature (PFV)/persistent hyperplastic primary vitreous (PHPV) |
| RIPK4 | AR | Popliteal pterygium syndrome (PPS) |
| PQBP1 | XLR | Renpenning's syndrome |
| RBP4 | AR | Retinal dystrophy, iris coloboma and comedogenic acne syndrome (RDCCAS) |
| DLX1, DLX2 | AD | Split-hand/foot malformation type V |
| C12orf57 | AR | Temtamy syndrome |
| WNT3 | AR | Tetra-amelia syndrome |
| SALL1 | AD | Townes–Brocks syndrome |
| PUF60 | AD | Verheij syndrome |
| RAB3GAP1, RAB3GAP2, RAB18, TBC1D20 | AR | Warburg Micro syndrome 1-4 |
Notes
- ↑ 1.0 1.1 AD: autosomal dominant; AR: autosomal recessive; XL: X-linked; XLD: X-linked dominant; XLR: X-linked recessive
References
- ↑ 1.0 1.1 1.2 1.3 "Microphthalmia" (in en). US National Library of Medicine. https://medlineplus.gov/genetics/condition/microphthalmia/.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 Eintracht J, Corton M, FitzPatrick D, Moosajee M (2020). "CUGC for syndromic microphthalmia including next-generation sequencing-based approaches.". Eur J Hum Genet 28 (5): 679–690. doi:10.1038/s41431-019-0565-4. PMID 31896778.
- ↑ George A, Cogliati T, Brooks BP (2020). "Genetics of syndromic ocular coloboma: CHARGE and COACH syndromes.". Exp Eye Res 193: 107940. doi:10.1016/j.exer.2020.107940. PMID 32032630.
- ↑ Ng D, Thakker N, Corcoran CM, Donnai D, Perveen R, Schneider A (2004). "Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR.". Nat Genet 36 (4): 411–6. doi:10.1038/ng1321. PMID 15004558.
- ↑ Blackburn PR, Zepeda-Mendoza CJ, Kruisselbrink TM, Schimmenti LA, García-Miñaur S, Palomares M (2019). "Variable expressivity of syndromic BMP4-related eye, brain, and digital anomalies: A review of the literature and description of three new cases.". Eur J Hum Genet 27 (9): 1379–1388. doi:10.1038/s41431-019-0423-4. PMID 31053785.
- ↑ van Rahden VA, Fernandez-Vizarra E, Alawi M, Brand K, Fellmann F, Horn D (2015). "Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome.". Am J Hum Genet 96 (4): 640–50. doi:10.1016/j.ajhg.2015.02.002. PMID 25772934.
- ↑ Vervoort VS, Viljoen D, Smart R, Suthers G, DuPont BR, Abbott A (2002). "Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation t(6;13)(q21;q12) and microcephaly, microphthalmia, ectrodactyly, prognathism (MMEP) phenotype.". J Med Genet 39 (12): 893–9. doi:10.1136/jmg.39.12.893. PMID 12471201.
- ↑ Casey J, Kawaguchi R, Morrissey M, Sun H, McGettigan P, Nielsen JE (2011). "First implication of STRA6 mutations in isolated anophthalmia, microphthalmia, and coloboma: a new dimension to the STRA6 phenotype.". Hum Mutat 32 (12): 1417–26. doi:10.1002/humu.21590. PMID 21901792.
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