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

We report on newborn monozygotic twins with a Noonan-like phenotype, and mu ltiple congenital anomalies due to a monocentric recombinant chromosome 18. The mother carried a paracentric inversion of the long arm of chromosome 1 8, inv(18)(q21.1q22.3). Cytogenetic, fluorescent in situ hybridization, com parative genomic hybridization and DNA marker analyses allowed the delineat ion of the deleted (18q22.3-qter) and duplicated (18q12.1-q21.1) chromosoma l regions in the recombinant chromosome 18, and suggest that this duplicati on-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 t he same chromosomal anomaly in these monozygotic twins. The clinical findin gs of these patients are compared with those reported in proximal 18q-dupli cation and distal 18q-deletion patients. The clinical features of both infa nts are compatible with Noonan syndrome, suggesting that a locus for this s yndrome may be located on the long arm of chromosome 18.