Syndromic microphthalmia


Syndromic microphthalmia is a class of rare congenital anomalies characterized by microphthalmia along with other non-ocular malformations. Syndromic microphthalmia accounts for 60 to 80% of all cases of microphthalmia. 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. There are 14 numbered syndromic microphthalmies primarily defined by their ocular manifestations:
TypeCausative gene/locusInheritance Synonyms
MCOPS1NAA10XLLenz microphthalmia syndrome
MCOPS2BCORXLRLenz microphthalmia syndrome
MCOPS2BCORXLDoculofaciocardiodental syndrome
MCOPS3SOX2ADSOX2 anophthalmia syndrome, anophthalmia/microphthalmia-esophageal atresia syndrome
MCOPS4Xq27-q28XLRmicrophthalmia-ankyloblepharon-intellectual disability syndrome
MCOPS5OTX2ADOTX2-related eye disorders
MCOPS6BMP4ADBakrania-Ragge syndrome, microphthalmia with brain and digit anomalies
MCOPS7HCCS, COX7B, NDUFB11XLDMIDAS syndrome, microphthalmia with linear skin defects syndrome
MCOPS8SNX3ADmicrocephaly-microphthalmia ectrodactyly of lower limbs and prognathism syndrome, Viljoen–Smart syndrome
MCOPS9STRA6ARanophthalmia/microphthalmia and pulmonary hypoplasia, Spear syndrome, Matthew–Wood syndrome
MCOPS10unknownmicrophthalmia and brain atrophy syndrome
MCOPS11VAX1ARN/A
MCOPS12RARBAD, ARmicrophthalmia with or without pulmonary hypoplasia, diaphragmatic hernia, and/or cardiac defects
MCOPS13HMGB3XLcolobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation, Maine microphthalmos
MCOPS14MAB21L2AD, ARcolobomatous 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: