The Ultimate Host

Dokan Mountain, Dokan Temple.

Dark refused to believe that his master was dead. Fuma showed him the proper way of the deathly ninja. The reason they called Dark because he was blind. He could"t see anything. Both of his eyes were white. He was born blind. He was born with LCA. (For those who don't know what LCA is.)

Leber congenital amaurosis (LCA) is a rare genetic eye disorder. Affected infants are often blind at birth. Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or a cone shape to the front of the eye (keratoconus). LCA is usually inherited as an autosomal recessive genetic condition.

Signs & Symptoms

Children born with LCA have light-gathering cells (rods and cones) of the retina that do not function properly. Absence or reduction of the electrical activity of the retina is always observed and is necessary for the diagnosis of LCA.

A decrease in visual responsiveness at birth is the first sign of the disease. Often the child will poke, press and rub the eyes to stimulate the retina to produce light (Franceschetti's oculo-digital sign). This activity may cause the eyes to become sunken or deep-set (enophthalmos).

Other symptoms may include strabismus; nystagmus; photophobia; cataracts; and/or keratoconus. In addition, some infants may exhibit hearing loss, intellectual disability, and/or developmental delay.

Specific types of LCA have been defined based on the causative gene. Some types are associated with little change in vision over time (stationary disease) while others become more severe over time (progressive disease).

Causes

LCA is a monogenic disease and at least 27 genes are implicated. Changes (mutations) in these genes can account for about 80-90% of diagnosed cases of LCA. The genes responsible for the remaining 10-20% of diagnoses are not known. LCA is usually inherited as an autosomal recessive genetic condition. Twenty-four of the genes associated with LCA cause only recessive disease. Two genes (IMPDH1 and OTX2) are known to cause a dominant disease. One gene (CRX) is known to cause either dominant or recessive disease, depending on the specific mutation.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

There are about 20,000 different genes in a human and all individuals carry one copy of several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

In rare cases, LCA is inherited as an autosomal dominant genetic disorder. Mutations in three genes, CRX, IMPDH1, and OTX2 are currently known to be associated with this type of LCA.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

Affected Populations

The prevalence of LCA has been estimated to be 1-2/100,000 births. This disorder affects males and females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to those of Leber congenital amaurosis. Comparisons may be useful for a differential diagnosis:

Loken-Senior syndrome is a rare autosomal recessive genetic disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. (For more information on this disorder, choose "Loken-Senior" as your search term in the Rare Disease Database.)

Joubert syndrome is an autosomal recessive genetic disorder that affects the area of the brain that controls balance and coordination. This condition is characterized by a specific finding on an MRI called a "molar tooth sign" in which the cerebellar vermis of the brain is absent or underdeveloped and the brain stem is abnormal. The most common features of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements, and low muscle tone.

Dark wished for sight. He wanted to kill the one who killed his master. However, he would have to keep the clan in check.