3.2.1 Stargardt et al

There are several frequently encountered hereditary eye diseases. Most of them are autosomal recessive, i.e., both parents are carriers. They include Stargardt's Disease, Usher Syndrome, and Leber's Congenital Amaurosis (LCA), among others. Still another common occurrence is retinoblastoma, caused by a deletion of the tumor suppressor gene Rb. Rb codes for a protein crucial in the regulation of the cell cycle.

These diseases each affects a different tissue of the eye:

Stargardt's disease can be regarded as juvenile macular degeneration. Similar to AMD, the end result is a dense central scotoma. And the gene culprit is abca4. The starting age of Stargardt's is usually around adolescence. Fortunately, these patients will never lose vision entirely. Their central vision may decrease to around 20/100 - 20/400, the peripheral vision is still quite normal. So proper optical aids can be of tremendous help to these children.

Usher Syndrome involves a form of retinitis pigmentosa, together with deafness. There are three types from the most severe USH1, to less severe USH2, and more moderate USH3. So far 12 loci are known to cause Usher Syndrome and seven of them and their proteins also have been identified. For your info: Genes for USH1 are MY07A, USH1C, CDH23, PCDH15, and SANS; for USH2: USH2A; and for USH3: USH3A. It is important to differentiate the types for counseling purposes. For example, USH1 patients with profound deafness will need to learn Braille prior to age 10 before their vision totally deteriorates.

Another of the worst possible cases is LCA, in which, there is no detectable photoreceptor activity at all. And the disease usually starts at birth or during early infancy. There are now 11 types identified, each associated with a mutation. And 14 genes are now known to be involved. There is a bright side: More recently, clinical trials of gene therapy for LCA caused by mutations in the RPE65 have begun. This is based on previous successful animal studies (dogs with the same RPE65 mutations) and should be very promising. This may pave the way for future treatment of genetic eye diseases. We shall find out soon enough.

And retinoblastoma is a cancer of the pediatric eye caused by deletions or mutation of Rb in the q14 band of chromosome 13. There are two types, the first is the familial retinoblastoma, in which both copies of defective Rb are present (i.e., one from each parent). There is another, unilateral retinoblastoma which is non-hereditary and not as severe; although no less cancerous. The treatment of retinoblastoma is similar to other cancers. Often the eyes must be removed to preserve life.

Here, I should point out that the practice of pediatric eyecare carries an enormous responsibility. Indeed, in all cases, accurate diagnosis is absolutely essential.

At present, not all clinics have access to PCR machines and the tests are quite costly as well. So genetic analysis is still not as widely available as it should. We hope this situation changes in the future. For now, by studying family history and examining symptoms, and signs, the latter through ophthalmoscopic observation, fundus photography, visual fields, etc, in conjunction with electrophysiological testing, such as ERG and VER, we can still draw very accurate road maps. Furthermore, in almost all cases with residual sights, the children can also be managed successfully through low-vision care.