Monosomy is a type of chromosomal aneuploidy characterized by the absence of one chromosome from a diploid pair, resulting in a total of 45 chromosomes in human cells instead of the typical 46.[1] This numerical abnormality disrupts the balanced genetic complement essential for normal development and function, often leading to severe developmental issues or embryonic lethality.[2]Monosomy typically arises from nondisjunction, a process where homologous chromosomes or sister chromatids fail to separate properly during meiosis I, meiosis II, or mitosis, producing gametes or cells with an abnormal chromosome number.[3] In humans, such errors occur sporadically in parental germ cells, with maternal nondisjunction being more common due to age-related declines in meiotic fidelity, though paternal contributions also play a role.[3] The resulting zygote inherits an unpaired chromosome, manifesting as monosomy across all or mosaic portions of the body.[4]Full monosomies are exceedingly rare in live births because they are generally incompatible with life, causing profound gene dosage imbalances that halt embryonic development early.[3] The only known viable full monosomy in humans is Turner syndrome (45,X), which affects approximately 1 in 2,000 to 2,500 female births and results from the loss of one X chromosome, leading to characteristic features such as short stature, ovarian dysgenesis, and cardiovascular anomalies.[5] Partial monosomies, involving deletions of chromosome segments, can also occur and are survivable in some cases, exemplified by cri-du-chat syndrome due to partial monosomy of the short arm of chromosome 5 (5p-), which presents with intellectual disability, microcephaly, and a distinctive cat-like cry.[3] These conditions highlight monosomy's role in a spectrum of genetic disorders, with diagnosis often relying on karyotyping or advanced genomic techniques.[2]
Fundamentals
Definition
Monosomy is a type of chromosomal abnormality classified under aneuploidy, characterized by the absence of one chromosome from a homologous pair in diploid organisms, leading to a total chromosome count of 2n-1 rather than the typical 2n.[6] This condition disrupts the normal genomic balance, as cells possess only a single copy of genes on the affected chromosome instead of the usual two.[1]Aneuploidy encompasses deviations in chromosome number, including both monosomy and trisomy.[7]Monosomy can be complete, involving the loss of an entire chromosome, or partial, where only a segment of the chromosome is deleted, leaving one full chromosome plus a portion of the second.[1] Complete monosomy results in the total absence of genetic material from that chromosome pair, whereas partial monosomy retains some but not all of the expected material, often due to deletions.[8]The concept of monosomy emerged in the early 20th century through foundational cytogenetic studies examining chromosome structures and numbers in various organisms.[9] In human genetics, it gained formal recognition following the 1959 identification of the chromosomal basis for Turner syndrome, which confirmed monosomy X as a viable condition in live births.[10] This breakthrough, building on earlier clinical descriptions from 1938, established monosomy as a key factor in genetic disorders.[11]In karyotype notation, monosomy is typically represented by indicating the reduced chromosome number and specifying the missing chromosome, such as 45,X for complete monosomy of the X chromosome in humans.[5] This standard nomenclature, part of the International System for Human Cytogenomic Nomenclature, facilitates precise communication of chromosomal configurations.[12]
Types
Monosomy is classified based on the chromosomes affected and the extent of the genetic material loss, distinguishing between autosomal and