Perinatal findings and molecular cytogenetic analysis of trisomy 16q and 22q13.3 deletion

Abstract

Objectives: To present the perinatal findings and molecular cytogenetic analysis of a case with concomitant trisomy 16q and 22q13.3 deletion of paternal origin.

Case and methods: A 24-year-old pregnant woman was referred at 30 weeks' gestation for suspected fetal abnormalities. Sonographic examination revealed decreased fetal movement, dolicocephaly, an asymmetric skull, and intrauterine growth restriction. Prenatal karyotyping was suggested but was declined. A female baby was delivered vaginally at 39 weeks' gestation with a body weight of 2180 g. The neonate presented generalized hypotonia with frequent apneic episodes and died at 1.5 months of age. Additional physical abnormalities included epicanthal folds, ptosis, frontal bossing with an enlarged metopic suture, bitemporal narrowing, hypertelorism, epicanthal folds, a pointed chin, micrognathia, prominent ears with preauricular pits, and clinodactyly. The karyotype from peripheral blood lymphocytes was 46,XX,der(22)t(16;22)(q12.1;q13.3)pat. The microdeletion at 22q13.3 was investigated by fluorescent in situ hybridization (FISH) analysis using the LSI DiGeorge/VCFS region/ARSA dual color DNA probe and the 22q telomeric probe, of which only the latter was able to detect the subtle deletion. Molecular analysis using polymorphic microsatellite markers indicated that the breakpoint at 22q13.31 was located between loci D22S1171 (present) and D22S1168 (absent).

Conclusion: The use of LSI DiGeorge/VCFS region/ARSA dual color DNA probes to examine distal 22q would miss some subtle terminal deletions of 22q13. However, the use of 22q telomeric probes would detect these minute deletions. Fetuses having trisomy 16q and 22q13.3 deletion may prenatally manifest decreased fetal movement, dolicocephaly, an asymmetric skull, and intrauterine growth restriction and postnatally present generalized hypotonia with frequent apneic episodes.