Clinical, cytogenetic, and molecular characterization of a girl with some clinical features of Down syndrome resulting from a pure partial trisomy 21q22.11-qter due to a de novo intrachromosomal duplication.

We report a girl with a de novo pure partial trisomy 21 with some clinical features of Down syndrome. The girl patient presented a flat broad face, brachycephaly, and a flat nasal bridge. She also had upwardly slanted palpebral fissures, epicanthal folds, blepharitis, brushfield spots, and strabismus. Her mouth was wide with downturned corners, prominent lower lip, narrow and furrowed tongue, and short palate. G-banded chromosomal analysis of metaphases in cells from both skin and blood showed a 46,XX karyotype with additional chromosomal material on the distal short arm of one chromosome 21. Parental chromosomes were normal. Molecular analyses with the short-tandem-repeat (STR) marker D21S2039 (interferon-alpha/beta receptor [IFNAR]) (21q22.1) showed a triallelic pattern. Subtelomeric fluorescent in situ hybridization (FISH) analyses, LSI 13 (retinoblastoma 1 [RB1])/LSI 21(21q22.13-q22.2), and whole chromosome painting probes specific for chromosome 21 showed trisomy for the segment 21q22.13-21q22.2 due to a de novo intrachromosomal duplication. A 500K SNP microarray analysis was then performed and revealed a 13-Mb duplication of 21q22.11-qter. This duplicated material had been translocated onto the end of the "p" arm of one of the chromosome 21s. The karyotype was provisionally defined as 46,XX,add(21)(p12).ish der (21)t(21;21)(p12;q22.11)(WCP21q+,PCP21q++,D215259/D21S341/D21S342++)dn. At the age of 4 years and 10 months, a comprehensive psychological examination was performed and the diagnostic criteria for mental retardation were not fulfilled. In comparison with previously published cases of pure partial trisomy 21, this is a rare finding. Additional studies of such rare patients should aid in the study of the pathogenesis of Down syndrome.

A 14-year follow-up of a case detected prenatally of partial trisomy 13q21.32-qter and monosomy 18q22.3-qter as a result of a maternal complex chromosome rearrangement involving chromosomes 6, 13, and 18.

A balanced complex chromosome rearrangement (CCR) involving three chromosomes is rare and may lead to different types of aneuploid germ cells. We report here a 14-year follow-up of a boy with a karyotype defined as 46,XY,der(18)t(6;13;18)(q21;q21.32;q22.3).ish der(18)(13qter+,18qter-) characterized by multiple congenital abnormalities, including distinctive minor facial anomalies, short neck, abnormalities of the extremities, anogenital abnormalities, flexion contractures, especially at extremities, and severe mental and growth retardation. Chromosome analysis in the mother showed a CCR involving chromosomes 6, 13, and 18. This CCR was the result of a three-break rearrangement, and the derivative chromosome 13 consisted of parts of chromosomes 18 and 13. The karyotype of the child was not balanced, and resulted in partial trisomy for 13q and partial monosomy for 18q detected prenatally by conventional and molecular cytogenetics. Although such a karyotype and its phenotype have not previously been reported, we have compared the clinical and cytogenetic data from our patient with previously described cases of partial trisomy 13q and monosomy 18q despite different break points. We are presenting a new CCR in a woman with normal phenotype with a history of four early abortions and a long follow-up of her malformed newborn with partial 13q trisomy and 18q monosomy.