Trisomy is a chromosomal abnormality defined by the presence of an extra copy of one chromosome, resulting in three copies instead of the typical two. Trisomy 7 is a relatively rare genetic condition where the body’s cells contain three copies of chromosome 7. This deviation disrupts the precise genetic balance required for typical development. Because chromosome 7 carries hundreds of genes, this extra genetic material often leads to severe developmental consequences.
The Genetic Basis of Trisomy 7
Human life relies on 23 pairs of chromosomes, with one set inherited from each parent. Chromosome 7 is a large non-sex chromosome (autosome), spanning approximately 160 million base pairs of DNA and containing an estimated 800 to 1,000 protein-coding genes. Trisomy 7 means an individual has three copies of this chromosome, leading to an over-expression of all its genes.
This extra chromosome copy arises from an error in cell division known as nondisjunction. Nondisjunction is the failure of chromosomes to properly separate during meiosis (formation of egg and sperm cells) or during mitosis (division of body cells after conception). If the error occurs during gamete formation, the fertilized egg carries the extra chromosome from the beginning. Errors happening later, during cell division in the early embryo, lead to a different and highly variable presentation of the condition.
Distinguishing Full and Mosaic Trisomy 7
The timing of the nondisjunction event determines whether an individual has Full Trisomy 7 or Mosaic Trisomy 7. Full Trisomy 7 is the most severe form, occurring very early in development so that every cell contains the extra chromosome 7. This comprehensive genetic imbalance is generally incompatible with life and almost always results in spontaneous miscarriage during early pregnancy.
Mosaic Trisomy 7 occurs later, during the post-fertilization mitotic divisions of the early embryo. This results in two distinct cell lines: one with the typical two copies of chromosome 7, and another with three copies. The outcome depends heavily on the percentage of trisomic cells and which specific tissues and organs are affected by the abnormal cell line.
The variable distribution of trisomic cells means that clinical outcomes can range dramatically, from severe health issues to largely unaffected cases. The condition can also manifest as confined placental mosaicism, where trisomic cells are isolated to the placenta but not present in the developing fetus. In these cases, the fetus may be genetically normal but still experience complications like intrauterine growth restriction due to placental dysfunction.
Clinical Manifestations and Prognosis
The clinical consequences of Trisomy 7 are directly linked to the proportion and location of the trisomic cells. Since Full Trisomy 7 is almost uniformly lethal early in development, the clinical focus centers on the highly variable manifestations of Mosaic Trisomy 7. The prognosis is guarded and requires careful monitoring.
Reported cases of Mosaic Trisomy 7 involve a wide spectrum of physical and developmental issues. These include prenatal and postnatal growth restriction, developmental delays, and intellectual disability. Severity correlates to the level of mosaicism in the nervous system.
Physical features can involve facial anomalies, such as frontal bossing and micrognathia, and unique skin pigmentary disorders that follow the lines of Blaschko on the body. Internal organ systems can also be affected, with cardiac defects and kidney abnormalities frequently observed.
In some instances, “trisomic rescue” occurs, where the embryo attempts to correct the trisomy by losing the extra chromosome 7. This can lead to maternal uniparental disomy 7, resulting in the inheritance of both copies of chromosome 7 from only the mother. This condition can lead to a phenotype resembling Silver-Russell syndrome, characterized by severe growth retardation.
Detection Methods and Diagnostic Screening
The initial detection of potential Trisomy 7 typically begins with Non-Invasive Prenatal Testing (NIPT). NIPT analyzes cell-free DNA from the placenta circulating in the mother’s blood. While effective for common trisomies, a positive result for a rare autosomal trisomy like Trisomy 7 requires further diagnostic confirmation. This screening result often reflects confined placental mosaicism rather than true fetal trisomy, necessitating follow-up testing.
To definitively diagnose the condition, invasive prenatal procedures like Chorionic Villus Sampling (CVS) or amniocentesis are necessary to obtain fetal or placental cells for genetic analysis. These samples are analyzed using karyotyping, which visually assesses chromosome number and structure, and Fluorescence In Situ Hybridization (FISH), which uses fluorescent probes to count chromosome 7 copies. Chromosomal microarray analysis (CMA) is also used to detect extra chromosomal material and is useful for identifying low-level mosaicism.