Prenatal diagnosis of an unexpected interstitial 22q11.2 deletion causing truncus arteriosus and thymic hypoplasia in a ring 22 chromosome derived from a maternally inherited paracentric inversion

Abstract

To present the prenatal diagnosis of an interstitial 22q11.2 deletion involving a ring 22 chromosome associated with truncus arteriosus and a hypoplastic thymus. Following the sonographic diagnosis of a cystic hygroma at 12 weeks of gestation, chromosome analysis revealed a ring 22 chromosome. Ring chromosomes typically result in the deletion of genetic material from the distal long and short arms of the affected chromosome. The presence of an interstitial deletion in a ring chromosome is therefore unusual. FISH analysis revealed an unexpected deletion involving the TUPLE1 gene in the DiGeorge/Velocardiofacial syndrome region in 22q11.2. Maternal chromosome analysis revealed the cause of the apparent interstitial deletion, a paracentric inversion in the long arm of chromosome 22, resulting in the distal long arm of 22q being located adjacent to the centromere and the proximal end being located near the telomere. The fetus was subsequently diagnosed with truncus arteriosus and a hypoplastic thymus, consistent with DiGeorge syndrome. The ring chromosome 22 found in the fetus appears to have been derived from a rearrangement of the mother's inverted 22, resulting in ring formation and loss of the end of the distal long arm of the inverted 22, including the TUPLE1 locus, causing DiGeorge syndrome in the fetus. The apparent interstitial deletion was actually a terminal deletion in a maternally inherited rearranged chromosome 22.