Nanophthalmos Plus Syndrome
Defective Genes
Clinical Characteristics
Ocular Features
This is a recently described type of nanophthalmos with characteristic clinical features plus retinal degeneration and optic disc drusen. Hyperopia is common and, like another recessive form of nanophthalmos (267760), patients have a progressive retinal dystrophy beginning with granular and mottled RPE changes and progressing to a bone spicule pattern resembling retinitis pigmentosa. No synechiae have been reported in this syndrome however. Macular retinoschisis and cystic changes with reduced foveal reflexes are commonly present. The anterior chamber and angles are narrow but no reported cases have had angle closure glaucoma such as frequently occurs in other forms of nanophthalmos (267760, 609549, 600165, 611897). Drusen of the optic nerve head can be demonstrated by ultrasound. Scleral and choroidal thickening are usually present. There is progressive deterioration of photoreceptors beginning with rod dysfunction and eventually involving cones as documented on ERG recordings. Nyctalopia and visual difficulties begin in childhood and the visual field is concentrically constricted. Visual acuity is in the range of 20/100 to 20/200.
Systemic Features
No systemic abnormalities have been reported.
Genetics
Inheritance
This is an autosomal recessive disorder caused by mutations in the membrane frizzled-related protein coding gene MFRP (11q23) expressed in retinal tissue. Both homozygous and compound heterozygous mutations have been described. It seems to be allelic to another nanophthalmos condition without retinal pigmentary degeneration which is caused by different mutations in MFRP (NNO2 609549). However, there is considerable clinical overlap of the several nanophthalmos conditions and it is possible that this is simply clinical heterogeneity within the same disease.
A syndromic form (MCOP5) of autosomal recessive microphthalmia with retinitis pigmentosa (611040) is also caused by mutations in MFRP and may be the same disorder.
For other forms of nanophthalmos see: 267760, 609549, 600165, 611897.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.