ISCN Nomenclature

The International System for Human Cytogenomic Nomenclature (ISCN) provides standardized rules for describing chromosomal findings from karyotyping, FISH, and microarray analysis. Mastery of ISCN nomenclature is essential for interpreting cytogenetic reports and communicating findings clearly between laboratories, clinicians, and patients.

Constitutional Karyotype Basics

• Normal karyotypes: 46,XX (female) or 46,XY (male). The total chromosome number is listed first, followed by the sex chromosomes.
• Numerical abnormalities:
  • Trisomy: 47,XX,+21 (female with trisomy 21 / Down syndrome)
  • Monosomy: 45,X (Turner syndrome; note: no second sex chromosome listed)
  • Triploidy: 69,XXX or 69,XXY

Structural Abnormalities

• Translocation, balanced reciprocal: t(breakpoint1;breakpoint2), e.g., 46,XY,t(11;22)(q23;q11.2), a balanced reciprocal translocation between chromosomes 11 and 22
• Robertsonian translocation: rob(chromosome;chromosome) or der(chromosome;chromosome), e.g., 45,XX,rob(13;14)(q10;q10), a Robertsonian translocation between chromosomes 13 and 14. Note the total count is 45.
• Deletion: del(chromosome)(breakpoints), e.g., 46,XX,del(5)(p15.2), terminal deletion of 5p (Cri-du-chat syndrome)
• Duplication: dup(chromosome)(breakpoints), e.g., 46,XY,dup(17)(p11.2p11.2), duplication of 17p11.2
• Inversion:
  • Paracentric (does not include centromere): inv(chromosome)(breakpoints on same arm), e.g., 46,XX,inv(3)(p21p26)
  • Pericentric (includes centromere): inv(chromosome)(breakpoints on different arms), e.g., 46,XY,inv(9)(p12q13); note: inv(9) is a common normal variant
• Derivative chromosome: der(chromosome), a structurally rearranged chromosome, typically the unbalanced product of a translocation. E.g., 47,XX,+der(22)t(11;22)(q23;q11.2) is the supernumerary derivative 22 from a parent carrying the balanced t(11;22), arising by 3:1 malsegregation (Emanuel syndrome)
• Ring chromosome: r(chromosome), e.g., 46,XY,r(20), ring chromosome 20
• Isochromosome: i(chromosome)(arm), e.g., 46,X,i(Xq), isochromosome for the long arm of X (both arms are q; loss of p)
• Marker chromosome: +mar, a small structurally abnormal chromosome of unknown origin. E.g., 47,XX,+mar

Mosaicism

• Mosaic notation: Use a forward slash between cell lines, with the number of cells in brackets. E.g., mos 47,XXX[15]/46,XX[5] indicates 15 cells with triple X and 5 cells with normal female karyotype.
• Constitutional vs acquired mosaicism: Constitutional (present from early development) vs acquired (e.g., somatic mutations in cancer). Cancer karyotypes use different conventions (clonal notation).

FISH Nomenclature

• Interphase FISH: nuc ish prefix, e.g., nuc ish(DXZ1x2), two copies of the X centromere probe (normal female)
• Microdeletion by FISH: ish del(22)(q11.2q11.2)(TUPLE1-) is deletion of the TUPLE1 probe at 22q11.2 (DiGeorge syndrome)
• Amplification: nuc ish(HER2x6), 6 copies of HER2 (amplification in breast cancer)

Array (CMA) Nomenclature

• Format: arr[build] region(coordinates)x copy number
• Deletion example: arr[GRCh38] 7q11.23(72,726,578_74,142,672)x1, single copy (deletion) at 7q11.23 (Williams syndrome)
• Duplication example: arr[GRCh38] 17p11.2(16,757,842_20,222,149)x3, three copies (duplication) at 17p11.2
• Absence of heterozygosity: arr[GRCh38] 15q11.2q13.1(25,051,657_32,445,302)x2 hmz, two copies but homozygous (possible UPD)

• Accurate communication: ISCN nomenclature ensures precise, unambiguous communication of cytogenetic results between laboratories and clinicians
• Report interpretation: Understanding nomenclature is essential for genetic counselors explaining results to patients and ordering appropriate follow-up testing
• Clinical fluency: Reading and translating ISCN strings is a routine, daily skill in cytogenetics practice

• Complexity: ISCN is extensive and updated periodically (most recent edition: ISCN 2024). Keeping current with changes can be challenging.
• Does not convey clinical significance: Nomenclature describes the finding but does not indicate whether it is pathogenic, benign, or of uncertain significance.
• Array nomenclature varies slightly: Different laboratories may use slightly different formatting for array results, though the core structure is standardized.