OMIM ID:
Optic Nerve Hypoplasia, Bilateral
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The hallmark of this syndrome is bilateral optic nerve dysplasia including aplasia and hypoplasia. It may occur in isolation or as part of other syndromes, especially in those having abnormalities of the central nervous system. All components of the nerve head are abnormally small including the entire disc area, the cup, and the neuroretinal rim. It has been reported that retinal vein tortuosity is predictive of patients with endocrinopathies. Retinal arteries often appear straight and narrow but this may not be seen in all cases. Visual acuity ranges from 20/50 to NLP but usually 20/200 or better. Many patients have nystagmus and strabismus.
This disorder shares many characteristics with septooptic dysplasia (182230) but the optic nerve anomalies are usually unilateral in the latter disorder and the disc rim often has a double margin. Mutations in different genes are responsible for the two disorders.
Systemic Features
Pituitary dysfunction and endocrinopathy may lead to life-threatening illness caused by adrenal crisis or hypoglycemia. An absent or abnormal septum pellucidum is present in 49% of patients and 64% have a hypothalamic-pituitary axis abnormality. Among those with an abnormal septum pellucidum, 56% have some kind of endocrinopathy. Other midline brain defects and cerebral anomalies have also been reported.
Genetics
Inheritance
Bilateral optic nerve hypoplasia is inherited in an autosomal dominant pattern based on the few families reported. Mutations in the PAX6 (11q13) gene are responsible.
A somewhat similar disease with extensive CNS and endocrinological abnormalities is septooptic dysplasia (182230) caused by mutations in the HESX1 gene.
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).
Autosomal dominant inheritance leads to a vertical pattern of transmission