Chromosomal duplications involve the formation of additional copies of a specific
chromosomal region, resulting in varying gene copy numbers within that region.
Duplications can impact the phenotype by altering gene dosage, as the amount of protein
synthesized is often proportional to the number of gene copies. Consequently, extra
genes can lead to an excess of proteins
1.
While full trisomies of chromosomes 13, 18, and 21 are the most commonly observed autosomal duplications at birth, other trisomies such as mosaic trisomy 8, trisomy 15q, and trisomy 17p have also been identified and are compatible with life.
Among these, mosaic trisomy 8 (T8MS), also known as Warkany Syndrome, is a rare chromosomal disorder characterized by the presence of an extra chromosome 8 in some cells. It exhibits distinct clinical features and an estimated incidence of 1 in 30,000 live births, stands out as a well-known syndrome associated with a range of developmental abnormalities. To date, approximately 121 cases have been reported in the literature, with a male-to-female ratio of 5:1. Most infants with T8MS have a normal life expectancy and birth weight. T8MS occurs due to postzygotic mitotic dissociation and manifests as a clinically heterogeneous syndrome 2,3. Common features associated with T8MS include dysmorphism, developmental delay, intellectual disability, cardiac and renal anomalies, agenesis of the corpus callosum, spinal deformity, scoliosis, hemivertebrae, contractures of the fingers and toes, and moderate mental retardation 4,5.
Duplication of chromosome 15q (dup15q), also known as trisomy 15q, is another rare chromosomal disorder that typically arises from unbalanced translocations resulting in 15q duplication. It was first described in 1974 by Fujimoto et al. 6, and at least 50 cases have been reported to date 7. Although the breakpoints in 15q duplications may vary, the general phenotype remains similar. Dup15q is characterized by craniofacial malformations, such as an elongated face, down slanting palpebral fissures, micrognathia, a long philtrum, a broad nasal bridge, a high-arched palate, short neck, malformations of the fingers and toes, skeletal malformations, genital abnormalities, and, in some cases, cardiac defects. Additional abnormalities typically include post- and pre-natal overgrowth, mild to profound intellectual disability, hypotonia, and motor delays 8,9. The severity of symptoms varies depending on the location and length of the duplicated portion of chromosome 15q 10.
Duplication of chromosome 17p is a rare chromosomal abnormality resulting in distinct clinical features, such as dysmorphic facial appearances (ptosis, malformed ears, and abnormality of the iris micrognathia, high-arched palate), prenatal and postnatal growth retardation, developmental delay, hypotonia, digital abnormalities, behavioral difficulties such as hyperactivity and autistic features, speech and language delay, intellectual disability, feeding difficulties, and congenital heart defects. Duplication 17p syndromes are classified into four groups based on the duplicated region 11: Group 1 involves an extra copy of short armband 17p11.2 and is known as Potocki-Lupski syndrome (PTLS). Group 2 involves duplication of band 17p11.2 and/or 17p12, usually showing features of PTLS with additional features 12,13. Group 3 involves an extra copy of short armband 17p13 and is known as 17p13 microduplication syndrome 14. Finally, group 4, known as trisomy 17p, involves a complete duplication of the short arm of 17p and is extremely rare 11.
This study aims to characterize the clinical and cytogenetic spectrum of four patients with rare chromosomal duplications involving mosaic trisomy 8, partial trisomy 15q, and partial trisomy 17p. By integrating conventional karyotyping with high-resolution molecular techniques, we seek to expand the known phenotypic spectrum and highlight the diagnostic challenges associated with these rare anomalies.
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