Towards mapping phenotypical traits in 18p- syndrome by array-based comparative genomic hybridisation and fluorescent in situ hybridisation.

Molecular karyotyping holds the promise of improving genotype-phenotype correlations for frequent chromosome conditions such as the 18p- syndrome. In spite of more than 150 reported cases with deletions in 18p, no reliable phenotype map for the characteristic clinical findings such as mental retardation, post-natal growth retardation and typical facial features has been established yet. Here, we report on four patients with partial monosomy 18p of different sizes owing to unbalanced translocations that were thoroughly characterised clinically and by molecular karyotyping. One patient had a terminal deletion of 1.6 Mb in 18p and a trisomy of 8q24.23-qter as determined by array-based comparative genomic hybridisation and large insert clone fluorescent in situ hybridisation. In two sibs and a fourth patient, cytogenetic and molecular-cytogenetic analyses showed the terminal deletions in 18p (8.0 and 13.84 Mb, respectively) to be accompanied by partial trisomies of 20p. Literature analyses of typical phenotypic features of 18p-, 8q+ and 20p+ syndromes allowed the attribution of clinical findings in our patients to the respective chromosomal aberration. Based on these data, we propose a phenotype map for several clinical features of the 18p- syndrome: Round face was tentatively mapped to the distal 1.6 Mb of 18p; post-natal growth retardation and seizures to the distal 8 Mb and ptosis and short neck to the proximal half of 18p.