MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: MFRP

NNO2
Nanophthalmos 2

Extreme hyperopia
Retinal thickening
Angle closure glaucoma
Retinal detachment

Nanophtalmos

Clinical Characteristics

General description (for patients): 

In this condition the eye is far shorter than normal and requires thick magnifying lenses for good vision.  The shortened eyeball increases the risk of glaucoma, especially the acute type known as angle-closure glaucoma requiring urgent surgery to prevent vision loss.

Medical description:  

Nanophthalmos results when the axial length of the eye is shortened from the normal range of 22-23 mm to 14-16 mm.  The extreme hyperopia requires +10 to +19 diopters of correction.  Since the retina and choroid size are normal but the internal scleral surface is decreased, folds often develop in these tissues.  Vascular flow is compromised and subretinal edema can occur, leading to detachment of the retina.  A more common problem is angle closure glaucoma as a result of crowding of anterior segment structures causing obstruction of the normal aqueous outflow through the trabecular meshwork.  Vision can be normal but is usually in the range of 20/40-20/60.

Genetics:

Only the autosomal recessive form of nanophthalmos has been found in Amish-Mennonites, and so far in only one extended family.  The mutation is a frameshift insertion, 1143C, in the MFRP gene on chromosome 11 (11q23.3).

Treatment: 

No treatment is available for the primary global malformation but surgical intervention in angle closure glaucoma and retinal detachment can be vision-saving.

Prognosis:

No associated systemic abnormalities have been found and, except for usually mild reduction in vision, patients lead normal lives.

Ancillary treatments and support:

Visual aids, low vision evaluations.

Specialists and specialty centers:

Ophthalmologist.

References:

Cross, H.E., and Yoder, F.:  Familial nanophthalmos.  Am. J. Ophthal. 81: 300-306.  PubMedID: 1258954

Sundin, O.H., Leppert, G.S., Silva, E.D., Yang, J.-M., Dharmaraj, S., Maumenee, I.H., Santos, L.C., Parsa, C.F., Traboulsi, E.I., Broman, K.W., DiBernardo, C., Sunness, J.S., Tory, J., and Weinberg, E.M.  Extreme hyperopia is the result of null mutations in MFRP, which encodes a frizzled-related protein.  Proc. Nat. Acad. Sci. 102: 9553-9558, 2005. PubMedID: 15976030

Resources:

Glaucoma Research Foundation
Prevent Blindness America