tetrasomy

Tetrasomy is a chromosomal condition in which cells contain four copies of a chromosome or a chromosome segment, instead of the usual two copies. In humans, tetrasomy can occur for autosomes or sex chromosomes and is typically a form of mosaic aneuploidy, arising from nondisjunction events during meiosis or mitosis, sometimes resulting in mosaic distribution across tissues. It is distinct from tetraploidy, where the entire genome is duplicated in all cells.

Examples of tetrasomy include tetrasomy 12p, as seen in Pallister-Killian syndrome, which results from mosaic presence of an isochromosome composed of two extra copies of 12p. Tetrasomy 18p involves an extra isochromosome carrying distal 18p material and can be mosaic or constitutional. Tetrasomy X, a rare sex-chromosome aneuploidy, involves four X chromosomes, typically described as 48,XXXX in affected individuals. Other autosomal tetrasomies or segmental tetrasomies may occur but are less well characterized.

Clinical features are variable and largely depend on which chromosome is involved and the extent of mosaicism. Commonly reported signs include developmental delay or intellectual disability, hypotonia, and congenital anomalies or dysmorphic features in some individuals. Because mosaicism can be tissue-specific, findings may differ between blood, skin, or other tissues.

Diagnosis relies on cytogenetic techniques. Conventional karyotyping can detect tetrasomy in cultured cells, but mosaic cases may require analysis of multiple tissues. Fluorescence in situ hybridization (FISH) and microarray-based methods can help confirm and delineate the duplicated region.

Management is supportive and multidisciplinary, focusing on developmental therapies, management of associated anomalies, and genetic counseling. Prognosis varies with the extent of mosaicism and the specific chromosome involved.