Table 1.
Overview of disease associated with non-syndromic and syndromic anophthalmia/severe microphthalmia
| Name of disease | Alternative names | OMIM# of the disease | Cytogenetic location | Associated gene(s) | OMIM# of associated gene(s) | Inheritance |
|---|---|---|---|---|---|---|
| Aniridia 1 (AN1) | Cataract, congenital, with late-onset corneal dystrophy | 106210 | 11p13 | PAX6 | 607108 | Autosomal dominant |
| Bosma arhinia microphthalmia syndrome (BAMS) | Arhinia, choanal atresia, microphthalmia and hypogonadotropic hypogonadism | 603457 | 18p11.32 | SMCHD1 | 614982 | Autosomal dominant |
| Branchiooculofacial syndrome |
BOF syndrome Branchial clefts with characteristic facies, growth retardation, imperforate, nasolacrimal duct and premature aging Hemangiomatous brancial clefts lip pseudocleft syndrome Lip pseudocleft hemangiomatous branchial cyst syndrome |
113620 | 6p24.3 | TFAP2A | 107580 | Autosomal dominant |
| Cerebrooculonasal syndrome | – | 605627 | Unknown | – | Unknown | Unknown |
| Chromosome 1q41-q42 deletion syndrome | Holoprosencephaly 10 (HPE10) | 612530 | 1q41-q42 | – | – | Isolated cases |
| COMMAD syndrome | Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness | 617306 | 3p13 | MITF | 156845 | Autosomal recessive |
| Dextrocardia with unusual facies and microphthalmia | – | 221950 | Unknown | – | – | Unknown |
| Focal dermal hypoplasia (FDH) |
FODH DHOF Goltz syndrome Goltz-gorlin syndrome |
305600 | Xp11.23 | PORCN | 300651 | X-linked dominant |
| Fraser syndrome 1 (FRASRS1) |
Fraser syndrome Cryptophtalmos with other malformations Cryptophthalmos- syndactyly syndrome |
219000 | 4q21.21 | FRAS1 | 607830 | Autosomal recessive |
| Fryns microphthalmia syndrome |
Microphthalmia with facial clefting Anophthalmia-plus syndrome |
600776 | Unknown | – | – | Autosomal recessive |
| Fryns syndrome (FRNS) | Diaphragmatic hernia, abnormal face, and distil limb anomalies | 229850 | Unknown | – | – | Unknown |
| Holoprosencephaly 9 (HPE9) |
Pituitary anomalies with holoprosencephaly-like features Holosproencephaly with microphthalmia and first branchial arch anomalies |
610829 | 2q14.2 | GLI2 | 165230 | Autosomal dominant |
| Joubert syndrome 21 | – | 615636 | 8q13.1-q13.2 | CSPP1 | 611654 | Autosomal recessive |
| Kapur-toriello syndrome | Long columella with cleft lip/palate and eye, heart and intestinal anomalies | 244300 | Unknown | – | – | Unknown |
| Linear skin defects with multiple congenital anomalies 1 (LSDMCA1) |
Microphthalmia, syndromic 7 (MCOPS7) Microphthalmia with linear skin defects (MLS) Microphthalmia, dermal aplasia, and sclerocornea Midas syndrome |
309801 | Xp22.2 | HCCS | 300056 | X-linked dominant |
| Manitoba oculotrichoanal syndrome (MOTA) | Marles syndrome | 248450 | 9q22.3 | FREM1 | 608944 | Autosomal recessive |
| Meckel syndrome, type 8 (MKS8) | – | 613885 | 12q24.31 | TCTN2 | 613846 | Autosomal recessive |
| Microphthalmia with limb anomalies (MLA) |
Waardenburg anophthalmia syndrome Anophthalmia- syndactyly Ophthalmoacromelic syndrome (OAS) |
206920 | 14q24.2 |
SMOC1 FNBP4 |
Autosomal recessive | |
| Microphthalmia, isolated 1 (MCOP1) |
MCOP Anophthalmia, clinical, isolated Microphthalmos, autosomal recessive |
251600 | 14q32 | – | – | Autosomal recessive |
| Microphthalmia, isolated 2 (MCOP2) | Anophthalmia, clinical, isolated | 610093 | 14q24.3 | VSX2 | 142993 | Autosomal recessive |
| Microphthalmia, isolated 3 (MCOP3) | – | 611038 | 18q21.32 | RAX | 601881 | Autosomal recessive |
| Microphthalmia, isolated 4 (MCOP4) | – | 613094 | 8q22.1 | GDF6 | 601147 | Autosomal dominant |
| Microphthalmia, isolated 8 (MCOP8) | – | 615113 | 15q26.3 | ALDH1A3 | 600463 | Autosomal recessive |
| Microphthalmia, isolated, with coloboma 3 (MCOPCB3) | Microphthalmia, cataracts and iris abnormalities | 610092 | 14q24.3 | VSX2 | 142993 | Autosomal recessive |
| Microphthalmia, isolated with coloboma 4 (MCOPCB4) | – | 251505 | Unknown | – | – | Unknown |
| Microphthalmia, isolated, with coloboma 10 (MCOPCB10) | – | 616428 | 10q23.33 | RBP4 | 180250 | Autosomal dominant |
| Microphthalmia, syndromic 1 (MCOPS1) |
Lenz microphthalmia syndrome Lenz dysplasia MAA |
309800 | Xq28 | NAA10 | 300013 | X-linked dominant and recessive |
| Microphthalmia, syndromic 2 (MCOPS2) |
Oculofaciocardiodental syndrome OFCD syndrome Microphthalmia, cataracts, radiculomegaly and septal heart defects ANOP2 MAA2 Lenz microphthalmia syndrome |
300166 | Xp11 | BCOR | 300485 | X-linked dominant and recessive |
| Microphthalmia, syndromic 3 (MCOPS3) |
Microphthalmia and esophageal atresia syndrome Clinical anophthalmia with assosicated anomalies Anophthalmia-esophageal genital syndrome AEG syndrome |
206900 | 3q26.33 | SOX2 | 184429 | Autosomal dominant |
| Microphthalmia, syndromic 4 (MCOPS4) |
Microphthalmia with ankyloblepharon and mental retardation Microphthalmia-ankyloblepharon-intellectual disability syndrome ANOP1 |
301590 | Xq27-q28 | – | – | X-linked recessive |
| Microphthalmia, syndromic 5 (MCOPS5) | Retinal dystrophy, early-onset, with or without pituitary dysfunction | 610125 | 14q22.3 | OTX2 | 600037 | Autosomal dominant |
| Microphthalmia, syndromic 6 (MCOPS6) |
Microphthlamia and pituitary anomalies Microphthalmia with brain and digit developmental anomalies Anophthalmia, clinical, with micrognathia, malformed ears, digital anomalies, and abnormal external genitalia |
607932 | 14q22.2 | BMP4 | 112262 | Autosomal dominant |
| 14q23.1 | SIX6 | 606326 | Autosomal recessive | |||
| Microphthalmia, syndromic 9 (MCOPS9) |
Anophthalmia, clinical, with mild facial dysmorphism and variable malformations of the lung, heart and diaphragm Anophthalmia/microphthalmia and pulmonary hypoplasia Pulmonary hypoplasia- diaphragmatic hernia- anophthalmia-cardiac defect (PDAC) Spear syndrome Matthew-wood syndrome Pulmonary agenesis, microphthalmia and diaphragmatic defect (PMD) Microphthalmia isolated with coloboma 8 (MCOPCB8) |
601186 | 15q24.1 | STRA6 | 610745 | Autosomal recessive |
| Microphthalmia, syndromic 11 (MCOPS11) | – | 614402 | 10q25.3 | VAX1 | 604294 | Autosomal recessive |
| Microphthalmia, syndromic 12 (MCOPS12) |
Microphthalmia with or without pulmonary hypoplasia diaphragmatic hernia and/or cardiac defects Matthew-wood syndrome |
615524 | 3p24.2 | RARB | 180220 | Autosomal dominant and recessive |
| Microphthalmia/coloboma and skeletal dysplasia syndrome (MCSKS) |
Microphthalmia or coloboma with or without rhizomelic skeletal dysplasia Microphthalmia, syndromic 14 (MCOPS14) |
615877 | 4q31.3 | MAB21L2 | 604357 | Autosomal dominant and recessive |
| Oculocerebrocutaneous syndrome (OCCS) |
Orbital cyst with cerebral and focal dermal malformations Delleman syndrome |
164180 | Unknown | – | – | Unknown |
| Sakoda complex |
Sphenoethmoidal encephalomeningocele agenesis of the corpus callosum and cleft lip/palate Sakoda spectrum |
610871 | Unknown | – | – | Unknown |
| Short-rib thoracic dysplasia 12 (SRTD12) |
Short rib-polydactyly syndrome, type IV (SRPS4) Beemer-langer syndrome Short rib syndrome, beemer type |
269860 | Unknown | – | – | Unknown |
| Thoracoabdominal syndrome (THAS) |
Midline defects, X-linked Pentalogy of cantrell |
313850 | Xq25-q26.1 | – | – | X-linked |