Noonan-like phenotype in monozygotic twins with a duplication-deficiency of the long arm of chromosome 18 resulting from a maternal paracentric inversion

Abstract

We report on newborn monozygotic twins with a Noonan-like phenotype, and multiple congenital anomalies due to a monocentric recombinant chromosome 18. The mother carried a paracentric inversion of the long arm of chromosome 18, inv(18)(q21.1q22.3). Cytogenetic, fluorescent in situ hybridization, comparative genomic hybridization and DNA marker analyses allowed the delineation of the deleted (18q22.3-qter) and duplicated (18q12.1-q21.1) chromosomal regions in the recombinant chromosome 18, and suggest that this duplication-deletion chromosome 18 resulted from breakage of a dicentric recombinant chromosome 18 with subsequent reconstitution of telomeric sequences on the long arm. Marked variability is observed in the phenotypic expression of the same chromosomal anomaly in these monozygotic twins. The clinical findings of these patients are compared with those reported in proximal 18q-duplication and distal 18q-deletion patients. The clinical features of both infants are compatible with Noonan syndrome, suggesting that a locus for this syndrome may be located on the long arm of chromosome 18.

Sperm studies in heterozygote inversion carriers: a review

“…Nevertheless, some cases of recombinant offspring from these carriers have been described (reviewed by Pettenati et al, 1995;Yang et al, 1997;Courtens et al, 1998;Whiteford et al, 2000;Lefort et al, 2002).…”

U-type exchange is the most frequent mechanism for inverted duplication with terminal deletion rearrangements

“…Since then, the application of molecular cytogenetic methods such as fluorescence in situ hybridisation (FISH) and array comparative genomic hybridisation (array CGH) has allowed for a significantly higher level of resolution for detecting and characterising chromosome abnormalities. As a result, the mechanisms responsible for this class of cytogenetic rearrangements have been better elucidated, and inverted duplication with concomitant terminal deletion has since been identified for a number of other chromosomes including 1p2 3 and 1q,4 2p,5 2q,6 3p,7 8 4p,9 10 11 and 4q,12 5p,13 14 7q,15 16 8p,17 18 19 20 9p21 and 9q,22 10p15 and 10q,15 11p,23 14q,8 24 25 15q,26 17p,27 18q,28 21q29 and Xp30 31 and in a variety of ring chromosomes 25 32…”

Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

“…In 2008 Cyril Gitiaux et al described the case of 2 sisters with autistic features, mental retardation, and hypotony, in whom the phenotypic features were not confirmed in genotype – ADSL (Adenylosuccinate lyase) deficiency [2,7]. …”