Syndromic microphthalmia

(Redirected from MMEP syndrome)

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.

Syndromic microphthalmia
SymptomsAbnormally small eyeball(s)
Usual onsetBirth[1]
DurationLifelong[1]
CausesGenetic or environmental factors[1]
Frequency1 in 10,000 individuals[1]

Classification

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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:

MCOPS classification
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]

Syndromes causing microphthalmia
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

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  1. ^ a b AD: autosomal dominant; AR: autosomal recessive; XL: X-linked; XLD: X-linked dominant; XLR: X-linked recessive

References

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  1. ^ a b c d "Microphthalmia". MedlinePlus. US National Library of Medicine. Retrieved 2021-11-04.
  2. ^ a b c d e f g h i j k l m 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. PMC 7171178. PMID 31896778.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ 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. PMC 7310839. PMID 32032630.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Ng D, Thakker N, Corcoran CM, Donnai D, Perveen R, Schneider A; et al. (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. S2CID 23628891.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Blackburn PR, Zepeda-Mendoza CJ, Kruisselbrink TM, Schimmenti LA, García-Miñaur S, Palomares M; et al. (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. PMC 6777538. PMID 31053785.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ van Rahden VA, Fernandez-Vizarra E, Alawi M, Brand K, Fellmann F, Horn D; et al. (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. PMC 4385192. PMID 25772934.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Vervoort VS, Viljoen D, Smart R, Suthers G, DuPont BR, Abbott A; et al. (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. PMC 1757218. PMID 12471201.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Casey J, Kawaguchi R, Morrissey M, Sun H, McGettigan P, Nielsen JE; et al. (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. PMC 3918001. PMID 21901792.{{cite journal}}: CS1 maint: multiple names: authors list (link)