Problems in diagnosis and delineation of inherited disorders in highly inbred populations

Two families were chosen as examples of the problems that may arise in the identification of inherited disorders in populations in which the rate of consanguineous marriages is high. In the first family, mentally retarded children of both sexes were born to 4 sisters married to close relative, and the possibility of an autosomal recessive disease was raised. The diagnosis of an X-linked disease, Martin Bell Syndrome, was made after the results of the chromosome analysis were at hand. In inbred communities, individuals affected with X-linked diseases are often born to parents who are related. In the second family two different autosomal recessive disorders were diagnosed among the children of a couple originating from a very inbred community. One of the children was affected with both disorders. The finding of two sibs with different symptoms may suggest that they have the same syndrome, and the differences in manifestations represent variability. The possibility that there may be more than one common abnormal gene in very inbred communities must be kept in mind, in particular when one is dealing with syndromes in which the diagnosis is based on clinical symptoms only. Another problem is that when the child has a complex unknown syndrome, the possibility that the child is affected simultaneously with 2 different genetic disorders should be raised.