Albinism
|
|
|
--%>
Clinical types
|
There are many types:
- Eye involvement only (ocular).
- Eye and skin involvement (oculocutaneous).
- Many syndromes featuring albinism along with other characteristics such as deafness, intestinal problems
(Hermansky-Pudiak type), immune system disorders (Chediak Higashi syndrome) and
other syndromes such as Prader Willi syndrome, etc.
|
Clinical signs
|
The common denominator in most types is the absence of pigment mainly in the fundus
of the eye, which can be seen on examination by an ophthalmologist. In most cases,
reduced pigmentation of the skin and sometimes of the hair is also present. The
majority of cases are in this category, but there is probably genetic heterogeneity
among these too. In other words, a number of different genes can cause albinism
affecting the skin and eyes. For example, one type of albinism features a deficiency
in the enzyme tyrosinase, the level of which can be measured in the patient-s hair,
whereas in another type of albinism the level of this enzyme is normal, etc.
There are rare types of albinism in which there are other features such as red hair,
deafness, etc. In these cases it is important to establish the exact diagnosis in
genetic institutes, after examination by a geneticist.
|
Inheritance pattern
|
In cases in which there are no metabolic effects other than albinism, the inheritance
is Autosomal
recessive. There is a relatively rare type of albinism that is restricted
to the eyes and is associated with deafness - this is transmitted by X-linked inheritance.
|
Penetrance
|
Varies according to type.
|
Associated features that can be demonstrated by imagery
|
Usually there are no defects that can be identified by ultrasound examination during pregnancy.
|
What is the risk of recurrence in a subsequent pregnancy?
|
According to the type of inheritance. The inheritance is autosomal recessive in
most cases, and a couple with one affected child has a 25% risk in each subsequent
pregnancy of having another affected child. With regard to more distant relatives,
the risk of having a child with the same condition is relatively low. Healthy siblings
of patients have a risk of less than 1 in 500 of having an affected child, and the
risk is even lower for more distant relatives.
|
Molecular genetic information
|
The genes for the disease
A number of genes associated with albinism have been found - in this table the different
types of disease have been arranged by gene type:
Genes associated with different types of albinism
|
Type of albinism (clinical term)
|
Name of gene
|
|
OCA1 (OCA1A and OCA1B)
|
Tyrosinase gene - chromosome 11
|
|
OCA2
|
P gene - chromosome 13
|
|
OCA3
|
TRP1 gene - chromosome 9
|
|
Hermansky-Pudlak Syndrome
|
HPS gene - chromosome 10
|
|
Chediak Higashi Syndrome
|
CHS gene - chromosome 11
|
|
X-linked ocular albinism
|
OA1 gene - X chromosome
|
|
Genetic testing
|
Diagnostic testing
|
|
|
If the mutation is not detected in such a test, or the patient is a member of an
ethnic group in which no common characteristic mutation is known, the genetic sequence
of a number of possible genes can be examined. This is an expensive and time-consuming
process that is not routinely performed apart from in special settings at centers
engaged in albinism research. See: Finding the defect
(mutation) by establishing the gene sequence - autosomal recessive diseases.
In all cases it is first necessary to establish a diagnosis with counseling and
testing at a genetic institute.
|
Carrier testing
To identify genes in the patient-s family
If the mutation has been found, other carriers in the extended family can be identified
with relative ease. If the mutation has not been found, the indirect tests specified
below in the section on fetal testing can be used provided that there are enough
affected family members. See: Indirect testing for genetic markers in a family that
has a number of patients - when there are a number of genes that can each cause
the disease - all genes having been located / identified / mapped - autosomal recessive
diseases. However, because of low risk and limited possibility of testing the partners,
these tests are not usually performed.
Carrier testing for partners of carriers in the general population
When a mutation has been found in a gene responsible for albinism in a patient in
a specific family, an attempt can be made to identify the mutations that are common
in that gene in the ethnic groups of the partners of the carriers. If a mutation
is not found in a partner, this does not completely rule out the possibility that
he or she is a carrier. In order to ascertain carrier status in members of the general
population, the sequence of the gene that is responsible for albinism in the affected
family member must be examined. This is a time-consuming and expensive test and
it is not performed routinely at the present time. See: Finding the defect
(mutation) by establishing the gene sequence - autosomal recessive diseases.
Fetal testing
When a couple has had one affected child, a relatively simple genetic test can be
used for prenatal testing of the fetuses in subsequent pregnancies. This is on condition
that the mutation in the albinism gene is found in the affected child and his or
her DNA is retained. If the mutation is not found and there are many affected individuals
in the family, indirect tests can also be employed. See: Indirect testing for genetic
markers in a family that has one or more patients - when there are a number of genes
that can cause the disease - autosomal recessive diseases.
Alternatively, a fetal skin biopsy test can be performed to test for cutaneous albinism
in utero. This test involves a 5% risk for miscarriage due to the procedure itself.
If the patient has another problem apart from albinism or the mutation is not found,
it is necessary to establish the diagnosis within counseling and testing at a genetic
institute.
|