Syndromic microphthalmia
Developmental disorder involving the eye
From Wikipedia, the free encyclopedia
Syndromic microphthalmia is a class of rare congenital anomalies characterized by microphthalmia along 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 based on 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 [a] | 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 [a] | 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
- AD: autosomal dominant; AR: autosomal recessive; XL: X-linked; XLD: X-linked dominant; XLR: X-linked recessive