Microdeletions are a group of clinically recognisable genetic disorders characterised by a small deletion of a chromosomal segment spanning multiple disease genes, each potentially contributing to the phenotype independently.
In the 1980’s, the development of in situ hybridation techniques, particularly those utilizing fluorescent markers (FISH), led to the discovery of the first cryptic deletion syndromes. This technique allowed precise localization of specific nucleic acid sequences on chromosomes or in tissues in order to understand the organization, regulation and function of genes. Subsequently, the detection of most microdeletion syndromes resulted from collaborations between clinicians, cytogeneticists and molecular geneticists.
The analysis of a genome can highlight the deletion of some parts of chromosomes. Microdeletions are identified by their genomic positions and their size. These deletions span one or several contiguous genes and can lead to a genetic disorder.
Most microdeletions have no clinical consequences, but some are characterized by a complex clinical and behavioural phenotype. Among the most common: DiGeorge syndrome, Cri Du Chat syndrome and Prader-Willi syndrome.
DiGeorge syndrome also called 22q11.2 deletion syndrome is a disorder caused by a defect in chromosome 22. It results in the poor development of several body systems. Common signs and symptoms include heart abnormalities present from birth (Tetralogy of Fallot), an opening in the roof of the mouth and distinctive facial features.
DiGeorge syndrome affects an estimated 1 in 4000 people. However, the condition may actually be more common than this estimate because doctors and researchers suspect it is underdiagnosed due to its variable features.
The deletion occurs most often as a random event during the formation of reproductive cells or in early fetal development. In about 10% of cases a person with this condition inherits the deletion in chromosome 22 from a parent. In inherited cases, other family members may be affected as well.
Cri Du Chat syndrome also known as 5p-syndrome or cat cry syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Childs with this condition often have a high pitched-cry that sounds like that of a cat, thus the name of the syndrome.
The disorder is characterized by intellectual disability and delayed development, microcephaly, low birth weight and weak muscle tone in infancy. Affected individuals also have distinctive facial features and some children are born with a heart defect.
Most cases of cri-du-chat syndrome are not inherited. The deletion occurs most often during the formation of reproductive cells or in early fetal development. About 10% of people with cri-du-chat syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost.
Cri-du-chat syndrome occurs in an estimated 1 in 20’000 to 50’000 newborns.
Prader-Willi syndrome is a complex genetic condition caused by the loss of function of genes in a particular region of chromosome 15 that affects many parts of the body.
In infancy, this condition is characterized by weak muscle tone, feeding difficulties, poor growth and delayed development. During childhood affected individuals develop an insatiable appetite which leads to chronic overeating and obesity.
People with Prader-Willi syndrome have mild to moderate intellectual impairment and learning disabilities. Behavioural problems are common including temper outbursts, stubbornness and sleep abnormalities can also occur. Puberty is delayed or incomplete and most affected individuals are unable to have children.
About 70% of cases of Prader-Willi syndrome occur when a segment of the paternal chromosome 15 is deleted in each cell. People with this chromosomal change are missing certain critical genes in this region because the genes on the paternal copy have been deleted and the genes on the maternal copy are turned off. In another 25% of cases, a person with Prader-Willi syndrome has 2 copies of chromosome 15 inherited from his or her mother instead of one copy of each parent.
Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. Affected people typically have no history of the disorder in their family.
Subchromosomal abnormalities (microdeletions and duplications) may result in physical and/or intellectual impairments that can be more severe than whole chromosome abnormalities.
Today, thanks to Prenatal cell-free fetal DNA screening, microdeletions and other chromosomal disorders such as Down syndrome are no longer hidden risks. These genetic tests empower doctors and patients with most relevant early actionable genetic information.
Tranquility is Genoma’s prenatal cell free DNA fetal screening test for trisomies and sexual aneuploidies that can also detect the most frequent microdeletions causing recognizable disorders.