Clinical Characteristics
Ocular Features
Three X-linked forms of progressive cone-rod dystrophies each with mutations in different genes have been identified. Central vision is often lost in the second or third decades of life but photophobia is usually noted before vision loss. Cones are primarily involved but rod degeneration occurs over time. The ERG reveals defective photopic responses early followed by a decrease in rod responses. All three types are rare disorders affecting primarily males with symptoms of decreased acuity, photophobia, loss of color vision, and myopia. The color vision defect early is incomplete but progressive cone degeneration eventually leads to achromatopsia. Peripheral visual fields are usually full until late in the disease when constriction and nightblindness are evident. The retina may have a tapetal-like sheen. RPE changes in the macula often give it a granular appearance and there may be a bull’s-eye configuration. Fine nystagmus may be present as well. The optic nerve often has some pallor beginning temporally. Carrier females can have some diminished acuity, myopia, RPE changes, and even photophobia but normal color vision and ERG responses at least among younger individuals.
There is considerable variation in the clinical signs and symptoms in the X-linked cone-rod dystrophies among both affected males and heterozygous females. Visual acuity varies widely and is to some extent age dependent. Vision can be normal into the fourth and fifth decades but may reach the count fingers level after that.
Systemic Features
None.
Genetics
Inheritance
Mutations in at least 3 genes on the X chromosome cause X-linked cone-rod dystrophy.
CORDX1 (304020) is caused by mutations in an alternative exon 15 (ORG15) of the RPGR gene (Xp11.4) which is also mutant in several forms of X-linked retinitis pigmentosa (300455, 300029). These disorders are sometimes considered examples of X-linked ocular disease resulting from a primary ciliary dyskinesia (244400).
CORDX2 (300085) is caused by mutations in an unidentified gene at Xq27. A single family has been reported.
CORDX3 (300476) results from mutations in CACNA1F. Mutations in the same gene also cause a form of congenital stationary night blindness, CSNB2A (300071). The latter, however, is a stationary disorder with significant nightblindness and mild dyschromatopsia, often with an adult onset, and is associated with high myopia. Aland Island Eye Disease (300600) is another allelic disorder.
Pedigree
X-linked dominant, father affected
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or renders him unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or at least renders them unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
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.