Structural Chromosome Abnormalities

This category of abnormalities includes several subclasses that will be discussed under separate headings. Again, as previously stated, all chromosomes involved in abnormalities are designated in numerical order, except for the X and Y, which are listed first.

When designating an abnormality that is limited to a single chromosome, the abbreviation for that abnormality is used, followed by the chromosome number in parentheses [e.g., r(X), del(2), ins(4), dup(5)]. If two or more chromosomes are involved in a rearrangement, as with translocations, a semicolon (;) is used to separate chromosome numbers within parentheses [e.g., t(3;4), t(2;5;10;) or t(15;17)]. Again, chromosomes are listed in numerical order unless a sex chromosome is involved [e.g., t(X;1) or t(Y;15)]. If, in the same cell, a specific chromosome is involved in both a numerical and a structural rearrangement, the numerical abnormality is designated first [e.g., +13,t(13;14)].

For ease of reference, the abnormalities covered will be presented in alphabetical order. For a thorough description of the mechanisms and clinical significance of structural chromosome abnormalities, see Chapter 9.

Additional Material, Origin Unknown (add)

When a chromosome has additional material attached to it, the origin of this material might not be identifiable with conventional banding methods. This is especially likely if the abnormality is subtle and originated de novo or is acquired. The abbreviation "add" (from the Latin additio) is used.

Additional material of unknown origin is attached to chromosome 17 at band p13. 46,XX,add(9)(q22)

Additional material of unknown origin attached to chromosome 9 at band q22. The region 9q22 ^ qter is missing and has been replaced by this material.

Deletions (del)

A deletion is an aberration in which a part of a chromosome is lost. Deletions can be either terminal, where all chromosomal material from the breakpoint on is lost, or interstitial, in which an internal section of one arm is missing. To introduce the reader to the long form of the nomenclature, a few of the following abnormalities will be presented using both the short and long forms.

Terminal Deletions

This karyotype describes a terminal deletion involving the long arm of chromosome 1. The colon present in the long form indicates a break at band 1q32 and deletion of the region distal to it. The rest of the chromosome, from 1pter to 1q32, is present.

Interstitial Deletions

Breakage and reunion are represented in the long form by a double colon (::). Here, this occurred involving bands 1p21 and 1p32. The segment between them has been deleted.

Derivative and Recombinant chromosomes

Derivative Chromosomes (der)

A structurally rearranged chromosome generated by events involving two or more chromosomes or the result of multiple events within a single chromosome is a derivative chromosome. Thus, each unbalanced product of a translocation event is a derivative chromosome. The identity of a derivative chromosome is determined by its centromere. Examples are as follows:

The derivative chromosome 3 in this example is the result of a translocation between the short arm of chromosome 3 at band p21 and the long arm of chromosome 6 at band q23. The der(3) replaces one normal chromosome 3, and both chromosomes 6 are normal. This unbalanced karyotype results in monosomy (loss) of region 3p21 ^ pter and trisomy (gain) of 6q23 ^ qter. This karyotype is the product of adjacent-1 segregation (see Chapter 9). 45,XY,der(3)t(3;6)(p21;q23),-6

The der(3) is same as in the above example and again replaces one of the normal chromosomes 3. However, there is only one normal chromosome 6 in the case, resulting in monosomy for both 3p21 ^ pter and 6pter ^ q23. This is the result of 3:1 segregation (see Chapter 9).

The der(3) is the same as in the above examples. A 3:1 segregation in the mother resulted in a normal 3 and the derivative 3 to be retained in the ovum. The father contributed a normal 3 as well. The patient is, therefore, trisomic for both3p21 ^ qter and 6q23 ^ qter.

Recombinant Chromosomes (rec)

Recombinant chromosomes are also structurally rearranged chromosomes. They arise de novo from meiotic crossing-over between homologous chromosomes when one is structurally abnormal, often, in an inversion heterozygote.

Take, for example, an individual with the karyotype 46,XY,inv(3)(p21q27). As described below, this man has one chromosome 3 with a pericentric inversion involving the segment between bands p21 and q27. During meiosis, crossing-over within the inverted segment could result in two recombinant chromosomes, each of which has a duplication of one part of the chromosome and deletion of another part; this is described in detail in Chapter 9:

One normal chromosome 3 has been replaced by a recombinant chromosome 3. The segment 3p21 ^ pter is duplicated, and the segment from 3q27 ^ qter is deleted. The key to interpreting this karyotype is "dup(3p)"; dup indicates a duplication (see Table 3).

Here, the other possible recombinant chromosome is present, resulting in duplication of the segment 3q27 ^ qter and loss of the segment 3p21 ^ pter. In this case, note "dup(3q)."

Fragile Sites

As discussed in Chapters 14 and 18, fragile sites exist in many areas of the human karyotype. Although the fragile site responsible for fragile X syndrome is no longer diagnosed via cytogenetic analysis, the nomenclature occasionally can still be seen. A male would be described as 46,Y,fra(X)(q27.3), and a female would be 46,X,fra(X)(q27.3). Other fragile sites are described in the same way [e.g., 46,XY,fra(12)(q13.1)].

Insertions (ins)

An insertion is a structural rearrangement in which a part of a chromosome is typically intersti-tially repositioned into a different area of the karyotype. Insertions can occur within a chromosome or between two chromosomes. They can also be direct, in which the inserted segment retains its orientation relative to the centromere, or inverted, where the inserted segment has been "flipped over." Although the symbols "dir" and "inv" can be used to distinguish between the two, they are optional, as the orientation of the inserted material is typically evident from the nomenclature.

Insertion Within a Chromosome

In these cases, only one chromosome need be described. The first band listed is the break at the point of insertion, followed by the breakpoints that define the inserted segment itself. No punctuation is used:


This represents a direct insertion. The long-arm segment between bands 3q27 and 3q32 has broken away and has been inserted into the short arm of the same chromosome at band p21. The orientation of the inverted segment has not changed (i.e., band q27 is still proximal to the centromere relative to band q32).


In this case, the inserted segment is inverted; band q32 is now closer to the centromere than band q27.

Insertion Between Two Chromosomes

Here, both chromosomes are listed, with the recipient chromosome presented first, irrespective of numerical order. As with other rearrangements, a semicolon separates the chromosome numbers.

The long-arm segment between bands 9q12 and 9q13 has been inserted, in its original orientation, into the long arm of chromosome 4 at band q31.

Inversions (inv)

A chromosomal aberration in which a segment of a chromosome is reversed in orientation but not relocated is called an inversion. There are two types of inversion. Paracentric inversions involve only one arm of a chromosome, whereas pericentric inversions involve both arms of a chromosome and, therefore, include the centromere. The type of inversion does not have to be specified, as this will be evident from the breakpoints.

Paracentric Inversions 46,XY,inv(3)(q21q27)

Break and reunion occurred at bands q21 and q27 in the long arm of chromosome 3. The segment lying between these breakpoints has been reattached with its bands in reverse (inverted) order.

Pericentric Inversions 46,XY,inv(2)(p21q31)

Break and reunion occurred at bands p21 (short arm) and q31 (long arm) of chromosome 2. The segment between these bands, including the centromere, was reattached with its bands in inverted order.

Isochromosomes (i)

An abnormal chromosome in which one arm is duplicated (and the other lost) is an isochromosome, abbreviated as "i" in the nomenclature. The breakpoint in an isochromosome is assigned to the centromere, at band p10 or q10, depending on which arm is duplicated:

This describes an isochromosome for the short arm of chromosome 18, as evident by assigning the breakpoint to band p10.

This describes an isochromosome for the long arm of a chromosome 18; the breakpoint is assigned to q10.

Isodicentric Chromosomes (idic)

Unlike isochromosomes, isodicentric chromosomes contain two copies of the same centromere. One of the two centromeres might be inactive, in which case the chromosome is pseudodicentric (psu dic). The breakpoints in isodicentric chromosomes are usually on the band adjacent to the centromere on the opposite arm:

Here, we have an isodicentric chromosome comprised of two copies of the entire short arm of chromosome 18, two copies of the centromere, and two copies of the small portion of the long arm between the centromere and band qll.2.

Marker Chromosomes (mar)

Marker chromosomes (mar) are supernumerary, structurally abnormal chromosomes of which no part can be identified. If any part of such a chromosome is identifiable, it is not a marker but a derivative chromosome. The presence of a "mar" in a karyotype is always recorded by a plus (+) sign:


This is a male karyotype with a marker chromosome.


This is a male karyotype with two marker chromosomes.

This describes a male karyotype with a translocation involving chromosomes 5 and 12, an extra chromosome 21, and a marker chromosome.

Ring Chromosomes (r)

A structurally abnormal chromosome with two breaks, one on the short arm and one on the long arm, in which the broken ends are attached to form a circular configuration is a ring chromosome. The net result is deletion of at least the terminal ends of both arms, and potentially more (or most) of either or both arms:

This is a female karyotype with only one normal X chromosome and a ring X chromosome with no information on breakpoints.

This describes a female karyotype with one normal X chromosome and a ring X chromosome with break and reunion at bands p22 and q24. The material distal to both breakpoints is lost.

Translocations (t)

The interchange or transfer of chromosomal segments between two nonhomologous chromosomes is defined as a translocation.

Reciprocal Translocations

If the translocation involves mutual exchange of segments between two chromosomes, it is referred to as a reciprocal translocation. To describe a reciprocal translocation, the abbreviation "rcp" can be substituted for the "t," but this is generally not done, as all translocations are, in one sense, theoretically reciprocal, even if this is not readily apparent visually. As always, sex chromosomes are listed first, with autosomes presented in numerical order. If a translocation involves three or more chromosomes, the same rule applies to the first chromosome listed; however, in these rearrangements, the second chromosome specified will be the one that received the segment from the first and so on:

Break and reunion occurred at bands 7q22 and 10q24. The segments distal to these bands were interchanged. The translocation event has not altered the total DNA content of this cell. Therefore, the translocation is microscopically (cytogenetically) balanced.

Break and reunion occurred at bands Xp21 and 1q32. The segments distal to these bands were interchanged. The translocation is balanced. Note that the X chromosome is specified first.

Break and reunion occurred at subbands Yq11.23 and 15q21.2. The segments distal to these bands were interchanged. This translocation is cytogenetically balanced. Here, again, the sex chromosome is specified first.

Break and reunion has occurred at bands 9q34 and 22q11.2. The segments distal to these bands have been interchanged. This represents the typical "Philadelphia" rearrangement associated with CML and also seen in ALL and AML.

This is an example of a complex translocation involving three chromosomes. The segment on chromosome 1 distal to band q32 has been translocated onto chromosome 7 at band p15, the segment on chromosome 7 distal to band p15 has been translocated onto chromosome 4 at band q21, and the segment on chromosome 4 distal to band q21 has been translocated onto chromosome 1 at band q32. The translocation is cytogenetically balanced.

These same general principles also apply to describing translocations involving more than three chromosomes.

Whole-Arm Translocations

Whole-arm translocations are a type of reciprocal translocation in which the entire arms of two nonacrocentric chromosomes are interchanged. Such rearrangements are described by assigning the breakpoints to the arbitrary centromeric regions designated as p10 or q10, as the actual ultimate composition of the centromeres is not known. If both chromosomes have exchanged the same arms, so that the resultant rearranged chromosomes are still comprised of one short arm and one long arm, the breakpoint p10 is assigned to the chromosome with the lowest number (or a sex chromosome, if applicable). Consequently, the other chromosome will have the breakpoint at q10:

This represents a balanced whole-arm translocation between chromosomes 3 and 8. In this example, the short arm of chromosome 3 and the long arm of chromosome 8 have been fused. Reciprocally, the long arm of chromosome 3 has fused with the short arm of chromosome 8, but only one combination need be written. The composition of the resultant centromeres is not known.

This is a balanced whole-arm translocation in which the short arms of chromosomes 3 and 8 have been fused, as have both long arms of these chromosomes. Note that the breakpoints designate the short arms of both chromosomes. Here, again, the reciprocal product [t(3;8)(q10;q10)] need not be written, as its presence is obvious from the chromosome number of 46.

Whole-arm translocations are not always balanced, as in the following examples:

Here, we have a derivative chromosome consisting of the short arm of an X and the long arm of chromosome 3. The reciprocal product consisting of the long arm of the X and the short arm of 3 is missing. Note: The total chromosome number is 45, indicating the loss of the reciprocal product; no (-) sign is used. The net result is monosomy for both the long arm of X and short arm of 3.

This karyotype has an extra derivative chromosome consisting of the short arm of an X and the long arm of chromosome 3, the same derivative chromosome as in the previous example. However, in this case, two normal X chromosomes and two normal chromosomes 3 are also present, and so the derivative chromosome is extra (note that the total number of chromosomes is 47). The net result is trisomy for both the short arm of the X and the long arm of chromosome 3.

Robertsonian Translocations

Although long believed to originate through centric fusion of the long arms of acrocentric chromosomes (pairs 13, 14, 15, 21, and 22), recent data suggest this might not always be so (see Chapter 9). They were first described by Robertson, whose name they have been given. The short arms, which all contain redundant copies of ribosomal genes, are lost in these rearrangements; this is of no clinical significance. Because Robertsonian translocations are still treated as a type of whole-arm translocation, they can be adequately described using the same nomenclature:

This describes a Robertsonian translocation between chromosomes 13 and 14. The centromere origin is unknown, and so the breakpoints are designated as 13q10 and 14q10 to indicate that both long arms are involved. This derivative chromosome has replaced one chromosome 13 and one chromosome 14; there is no need to indicate the missing chromosomes. The karyotype now contains one normal 13, one normal 14, and the der(13;14). The short arms of the 13 and 14 are lost, which is why the abbreviation "der" is used instead of "t" to describe the translocation. One can also use "rob" to describe Robertsonian translocations. The loss of these short arms is not clinically significant and, therefore, this description represents a balanced Robertsonian translocation (an individual with this karyotype is referred to as a balanced carrier) even though only 45 chromosomes are present.

The derivative chromosome consists of the long arms of chromosomes 13 and 14, as in the above example. However, in this karyotype, there are two normal 13s and one normal 14, plus the der(13;14). The net result is trisomy for the long arm of chromosome 13, clinically identical to trisomy 13. The additional chromosome 13 is shown by the designation +13. Here, we have an example of both numerical and structural abnormalities that involve the same chromosome number, and so the numerical abnormality is designated first.

Uniparental Disomy (upd)

Representation of both maternally and paternally inherited genes is required in many areas of the genome in order for normal development to occur. This phenomenon is referred to as genomic imprinting and involves selective inactivation of certain genes by methylation. Uniparental disomy is a situation in which both homologs of a specific chromosome pair are inherited from the same parent and, in some cases, is associated with an abnormal phenotype. Uniparental disomy can occur, for example, in an embryo that starts out trisomic for a given chromosome and then loses one copy of this chromosome early enough in development to "rescue" what would have been a pregnancy doomed to abort spontaneously. If, by chance, the two remaining copies were inherited from one parent, the individual is said to have upd for that chromosome. For example, some patients with Prader-Willi/ Angelman syndrome and no deletion of chromosome 15 have been shown to have upd for this chromosome. Inheriting two paternal chromosomes 15 results in Angelman syndrome, whereas receiving two maternal 15s results in Prader-Willi syndrome. See Chapter 19.

Nomenclature examples are follows:


This is a male patient with uniparental disomy for paternally derived chromosomes 15.

This represents a mosaic male karyotype involving one cell line that contains two paternally derived chromosomes 22 and the other with trisomy 22. Here, both cell lines are abnormal and, therefore, the larger clone is recorded first.

46,XX,upd pat

This describes a complete hydatidiform mole with XX sex chromosomes (very rare). All 46 chromosomes are paternally derived.

46,XY,upd pat

This describes a complete hydatidiform mole with XY sex chromosomes. All 46 chromosomes are paternally derived.

46,XX,upd mat

This is an ovarian teratoma. All 46 chromosomes are maternally derived. NEOPLASIA

The basic rules for using the nomenclature apply when describing the karyotypes associated with cancer. However, special situations, requiring additional guidelines, might arise in these cases. Therefore, special ISCN definitions and rules have been devised for use with neoplasia.

A clone is defined as two cells that share the same abnormality or abnormalities, unless the change involves loss of a chromosome, in which case three such cells are required (because of the possibility of coincidental random chromosome loss). During tumor progression, related subclones can evolve; related or unrelated clones are separated by slashes "/" and the number of cells observed for each is given in square brackets "[ ]".

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