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Microphthalmia, Syndromic 5

OMIM ID:

autosomal dominant

Microphthalmia, Syndromic 5

Alternate Names

MCOPS5

Defective Genes

OTX2

Clinical Characteristics

Ocular Features

One or both eyes may be small, sometimes resembling clinical anophthalmia. Other ocular anomalies such as coloboma, microcornea, cataracts, and hypoplasia or agenesis of the optic nerve have been reported.

A pigmentary retinopathy has been described.  The retinal vessels are often attenuated and sometimes sparse.  The optic nerves and chiasm are frequently absent or hypoplastic as seen on the MRI.  ERG and VEP responses are inconsistent but are generally abnormal indicating photoreceptor malfunction.  

Systemic Features

Patients have a variety of systemic abnormalities including pituitary dysfunction, joint laxity, hypotonia, agenesis of the corpus callosum, and seizures.  Hypothyroidism and deficiencies of growth hormone, gonadotropins, and cortisol are present in some patients.  Developmental delay and cognitive impairment are frequently present but mental functioning is normal in some patients.  The genitalia of males are often underdeveloped.  Patients are often short in stature.

Genetics

Inheritance

This is an autosomal dominant condition secondary to heterozygous mutations in the OTX2 gene (14q22.3).  A variety of point mutations as well as microdeletions involving the OTX2 gene have been reported.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

There is no treatment for the syndrome but surgical and/or endocrinological treatment may be used to correct individual features.  Special education and low vision aids may be helpful in selected patients.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction

PubMedID: 19956411

Heterozygous Mutations of OTX2 Cause Severe Ocular Malformations

PubMedID: 15846561