Clinical Characteristics
Ocular Features
The unique status of this type of X-linked cataract is uncertain as the phenotype is highly variable. It is listed separately in this database because some patients do not have the dysmorphic features of Nance-Horan syndrome (302350) which also is caused by mutations in the NHS gene. Lens opacities in males usually occur in the nucleus which may cause severe visual impairment. Heterozygous females have granular opacities along the Y sutures but these may also be seen in males. Microcornea, variable microphthalmia, and congenital glaucoma (usually secondary) have been noted in a few patients.
Systemic Features
Facial dysmorphology, intellectual impairment, and dental anomalies are often found in patients with X-linked cataracts as part of the Nance-Horan syndrome (302350). However, these signs may not always be apparent and therefore were not reported in early publications which adds uncertainty to the classification. That said it is also true that some families in which X-linked cataracts segregate do not have the systemic features in spite of detailed examinations even though they have mutations in NHS.
Genetics
Inheritance
A mutation in the NHS gene (Xp22.13) can be responsible for X-linked cataracts. Mutations in the same gene cause Nance-Horan syndrome (302350). Individuals with typical X-linked cataracts, however, may or may not have systemic malformations.
A variety of alterations in the NHS gene, including copy number variations, intragenic deletions, and duplication/triplication arrangements, have been found and are likely responsible for the clinical heterogeneity and current nosological confusion. Until additional fine genotyping is available for more patients it is not possible to determine if a category of X-linked cataracts without NHS mutations exists.
Pedigree
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.