Megalocornea, Ectopia Lentis, and Spherophakia
Defective Genes
Clinical Characteristics
Ocular Features
Patients have megalocornea and mobile lenses. Corneal diameters are at least 13 mm in diameter. Some lenses are spherophakic (refractive errors may be in the +11-12 diopter range) and sometimes displace into the anterior chamber or cause pupillary block glaucoma. The clinical picture often resembles congenital glaucoma in young children but the elevated pressure is usually secondary to hypermobility of the lens and/or its spherical shape. Haab striae are not present but cloudy corneas have been reported in a few patients.
Many patients develop phthisis or have severe reductions in vision.
Systemic Features
Some but not all patients have several physical features of the Marfan syndrome (154700) such as high arched palate, tall stature, and narrow face but those tested do not have mutations in the FBN1 gene.
Genetics
Inheritance
This is an autosomal recessive disorder. Parental consanguinity is common. Homozygous mutations in the LTBP2 gene (14q24.3) are found in affected individuals.
LTBP2 competes with LTBP1 (ADAMTSL2) for binding to the gene product of FBN1 in which mutations are associated with the Marfan syndrome (154700) and may account for the variable skeletal signs sometimes found in patients with this megalocornea syndrome. Both gene products are important to the structure of the extracellular matrix proteins of the ciliary processes, lens capsule, and lens epithelial layer. The different modes of inheritance and the unique mutations, of course, argue for separateness of the two disorders.
Mutations in LTBP2 have also been found in a family with microspherophakia and ectopia lentis but corneal diameters were described as normal suggesting clinical heterogeneity.
This is a unique disorder which previously has been classified as Glaucoma, Congenital Primary D (613086). The usual occurrence of ectopia lentis, the sometimes spherophakic nature of the lenses, the congenital presence of megalocornea without corneal edema in the absence of elevated intraocular pressure, and the lack of breaks in the Descemet membrane strongly suggest that this is not a primary congenital glaucoma.
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.