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

• Published in: Human genetics 1998-10, Vol.103 (4), p.497-505
• Main Authors: COURTENS, W, GROSSMAN, D, SPELEMAN, F, VAN ROY, N, MESSIAEN, L, VAMOS, E, TOPPET, V, HAUMONT, D, STREYDIO, C, JAUCH, A, VERMEESCH, J. R
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chromosome Deletion; Chromosome Inversion; Chromosomes, Human, Pair 18; Diseases of the osteoarticular system; Humans; In Situ Hybridization, Fluorescence; Infant, Newborn; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Microsatellite Repeats; Mothers; Noonan Syndrome - genetics; Phenotype; Twins, Monozygotic - genetics
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390050857

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.