Abstract for presentation at 11th International Congress of Human Genetics

Phelan-McDermid syndrome is a microdeletion syndrome associated with loss of the distal long arm segment 22q13.3. We have studied the segregation of a translocation between the long arm of chromosome 19 and the long arm of chromosome 22 through six generations of a family. The chromosome breakpoints were 19q13.4 and 22q13.3. G-banded chromosome analysis was performed on eleven individuals in four generations. FISH was performed using commercially available probes for ARSA and/or the subtelomeric regions of chromosomes 19 and 22 to confirm the cytogenetic findings. Individuals who were not available for chromosomes studies were considered as obligate balanced translocation carriers based on the birth of offspring who tested positive for balanced or unbalanced rearrangements. Results showed that fourteen individuals from generations I through V were balanced translocation carriers. Three individuals in generations V and VI tested positive for the unbalanced translocation and had typical features of Phelan-McDermid syndrome including neonatal hypotonia, moderate to profound developmental delay, absent or severely delayed speech, and minor dysmorphic features. Seven additional family members from generations II through IV were suspected of having the unbalanced translocation based on phenotypic features. The majority of individuals with Phelan-McDermid syndrome have simple deletions of chromosome 22. The remaining deletions are due to unbalanced translocations, ring chromosomes, or rare cases of recombinants of chromosome 22. About 80% unbalanced translocations associated with deletion 22q13.3 result from mal-segregation of parental translocations. This is the first study demonstrating segregation of a balanced translocation in several generations resulting in the birth of multiple offspring affected with Phelan-McDermid syndrome.