OMIM ID:
Lowe Oculocerebrorenal Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Lens development is abnormal from the beginning secondary to abnormal migration of lens epithelium which has been described in fetuses by 20-24 weeks of gestation. This leads to some degree of opacification in 100% of affected males. The lens opacities may be polar or nuclear in location but complete opacification also occurs. Leukocoria, miosis, microphthalmos and a shallow anterior chamber has been noted in neonates. The cataractous lenses may be small and abnormally formed. Glaucoma is present in more than half of affected males with onset by the age of 6 years and may be difficult to control. Conjunctival and corneal keloids are found in about one-fourth of patients.
Adult female carriers characteristically have peripheral cortical opacities, appearing in a radial configuration. These ‘snowflake’ opacities seldom cause visual symptoms. It has been proposed that slit lamp examinations for such opacities can accurately determine the carrier status of females.
Systemic Features
Mental retardation, hypotonia, short stature, and developmental delays are common. Seizures and behavior problems are seen in older children. The renal defect secondary to defective phosphatidylinositol 4, 5-biphosphate 5- phosphatase results in a Fanconi-type aminoaciduria beginning late in the first year of life. The phosphaturia leads to hypophosphatemia and eventually renal rickets. Proteinuria, polyuria, as well as bicarbonate, sodium and potassium wasting with tubular acidosis are all part of the urinary profile. Some patients have dental cysts and/or defective dentin.
Genetics
Inheritance
The mutation causing this X-linked disorder is in the OCRL gene located at Xq26.1. New mutations have been found among nearly one-third of affected males.
Another X-linked disorder with similar but less severe kidney disease, Dent disease 2 (300555), has been found to have mutations in the same gene. However, none of the ocular features are present.
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.