Isodicentric 15
Encyclopedia
Isodicentric 15, also called idic(15), partial tetrasomy 15q, or inverted duplication 15 (inv dup 15), is a chromosome abnormality
in which a child is born with extra genetic material from chromosome 15
. People with idic(15) are typically born with 47 chromosomes in their body cells, instead of the normal 46. The extra chromosome is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). Individuals with idic(15) have a total of four copies of this chromosome 15 region instead of the usual two copies (1 copy each on the maternal and paternal chromosomes).
The extra chromosome is rarely found in mosaic
state, i.e. some of the cells carry the marker chromosome. However, mostly because of the marker's instability and tendency to be lost during cell division (mitosis
), some cells are completely normal with 46 chromosomes. Occasionally, cells may have more than one idic(15), resulting in 48 or 49 chromosomes in all or some of their cells. A similar clinical picture albeit to a milder degree could be expected in individuals that have the extra chromosome 15 material as an interstitial duplication; not as a marker chromosome; thus having 46 chromosomes.
), seizures, short stature, and mental retardation
. Distinctive facial features associated with idic(15) may include epicanthal fold
s (skin fold
s at the inner corners of the eyes), a flattened nasal bridge, button nose, and a high arched palate
(roof of the mouth). Some individuals with idic(15) also have features of autism
, such as problems with communication, social interactions, and repetitive and stereotyped behaviors (e.g., lining up toys, playing with a toy in the same manner over and over again, hand flapping, rocking back and forth). These are some mild features but with a severe person there may be more such as inability to talk at all.
; in one member of the family, by chance. In most cases, the abnormal chromosome is generated in the mother's germ cells; oocyte
s. This finding is due to ascertainment bias; i.e. cases with maternally derived idic(15) usually have clinical findings and attract attention but those with paternally derived idic(15) usually do not. Thus, established cases are usually patients with maternally inherited idic (15).
People with idic(15) have extra genetic material that has developed from chromosome 15. The material usually exists as a little extra chromosome 15; which is called marker chromosome
or extra structurally abnormal chromosome (ESAC). The marker usually exists as an isodicentric chromosome; i.e. 2 copies of a specific part of the long arm of chromosome 15 (most commonly, 15q11-q13) that is mirrored and doubled, with 2 centromere
s and 2 DNA satellite
s. The smallest markers appear to be harmless and they may go undetected. However, if they are large enough to contain a number of important genes, they may result in "idic(15) syndrome" which is characterized by mental retardation, autism
and other neurological symptoms. One of the regions responsible for the symptoms of idic(15)syndrome is the critical PWS/AS-region named after the Prader-Willi and/or Angelman syndromes.
) is used to confirm the diagnosis by distinguishing idic(15) from other supernumerary marker chromosomes. Array CGH could be used to determine the gene content and dosage so that clinical picture could be foreseen.
Interstitial duplications of chromosome 15 can be more difficult to detect on a routine chromosome analysis but are clearly identifiable using a 15q FISH study. Families should always discuss the results of chromosome and FISH studies with a genetic counselor or other genetics professionals to ensure accurate interpretation.
. (A chromosome anomaly involves extra or missing chromosomal material, not changes within the genes such as Fragile X syndrome
). It is suggested that the co-occurrence of autism and idic(15) is not by chance. There may be a gene or genes in the 15q11-q13 region that is/are related to the development of autism in some individuals.
Genetic research studies of individuals without chromosome anomalies also support this idea that an autism
-related gene may be present in 15q11-q13. Specifically, research studies found that certain DNA
markers from the 15q11-q13 region were found more often in individuals with autism than in individuals without autism. Although these DNA markers are too small to be genes, they suggest that researchers may be getting close to finding an autism gene in this region.
In terms of medical management of the symptoms associated with dup15q syndrome, families should be aware that individuals with chromosome 15 duplications may tolerate medications differently and may be more sensitive to side effects for some classes of medications, such as the serotonin reuptake inhibitor type medications (SSRI).
Thus, these should be used with caution and any new medication should be instituted in a controlled setting, with slow titration of levels and with a clear endpoint as to what the expected outcome for treatment is.
but the parents must be karyotyped to make sure it is not inherited, mostly because this will affect the course of genetic counseling
given to the family. If the abnormality is found prenatally and one of the parents harbour the marker, the child has a chance of being normal. Further tests should however be done to prove the marker has not been rearranged while being inherited. This information is also necessary for counseling of future pregnancies. Each family is unique and should therefore be handled individually.
Chromosome abnormalities
A chromosome anomaly, abnormality or aberration reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes. A Karyotype refers to a full set of chromosomes from an individual which can be compared to a "normal" Karyotype for the species via genetic testing. A...
in which a child is born with extra genetic material from chromosome 15
Chromosome 15 (human)
right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
. People with idic(15) are typically born with 47 chromosomes in their body cells, instead of the normal 46. The extra chromosome is made up of a piece of chromosome 15 that has been duplicated end-to-end like a mirror image. It is the presence of this extra genetic material that is thought to account for the symptoms seen in some people with idic(15). Individuals with idic(15) have a total of four copies of this chromosome 15 region instead of the usual two copies (1 copy each on the maternal and paternal chromosomes).
The extra chromosome is rarely found in mosaic
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
state, i.e. some of the cells carry the marker chromosome. However, mostly because of the marker's instability and tendency to be lost during cell division (mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
), some cells are completely normal with 46 chromosomes. Occasionally, cells may have more than one idic(15), resulting in 48 or 49 chromosomes in all or some of their cells. A similar clinical picture albeit to a milder degree could be expected in individuals that have the extra chromosome 15 material as an interstitial duplication; not as a marker chromosome; thus having 46 chromosomes.
Signs and symptoms
Individuals with idic(15) have delays in language development and motor skills such as walking or sitting up. Other traits may include low muscle tone (hypotoniaHypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
), seizures, short stature, and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. Distinctive facial features associated with idic(15) may include epicanthal fold
Epicanthal fold
An epicanthic fold, epicanthal fold, or epicanthus is a skin fold of the upper eyelid, covering the inner corner of the eye....
s (skin fold
Skin fold
Skin folds are areas of skin where it folds. Many skin folds are distinct, heritable anatomical features, and may be used for identification of animal species, while others are non-specific and may be produced either by individual development of an organism or by arbitrary application of force to...
s at the inner corners of the eyes), a flattened nasal bridge, button nose, and a high arched palate
Palate
The palate is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but, in most other tetrapods, the oral and nasal cavities are not truly separate. The palate is divided into two parts, the anterior...
(roof of the mouth). Some individuals with idic(15) also have features of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, such as problems with communication, social interactions, and repetitive and stereotyped behaviors (e.g., lining up toys, playing with a toy in the same manner over and over again, hand flapping, rocking back and forth). These are some mild features but with a severe person there may be more such as inability to talk at all.
Epidemiology
About half of all marker chromosomes are idic(15) but idic (15) in itself is one of the rare chromosome abnormalities. It is estimated that 1 out of 8000 babies are affected. This number includes the children with a large IDIC (15) marker as well as children with a small marker (without negative phenomena). There are organizations for families with idic(15) children that offer extensive information and support.Genetics
Generally, idic(15) is not inherited; it is said to appear de novoDe novo
In general usage, de novo is a Latin expression meaning "from the beginning," "afresh," "anew," "beginning again." It is used in:* De novo transcriptome assembly, the method of creating a transcriptome without a reference genome...
; in one member of the family, by chance. In most cases, the abnormal chromosome is generated in the mother's germ cells; oocyte
Oocyte
An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...
s. This finding is due to ascertainment bias; i.e. cases with maternally derived idic(15) usually have clinical findings and attract attention but those with paternally derived idic(15) usually do not. Thus, established cases are usually patients with maternally inherited idic (15).
People with idic(15) have extra genetic material that has developed from chromosome 15. The material usually exists as a little extra chromosome 15; which is called marker chromosome
Marker chromosome
A marker chromosome is a structurally abnormal chromosome in which no part can be identified. The significance of a marker is very variable as it depends on what material is contained within the marker....
or extra structurally abnormal chromosome (ESAC). The marker usually exists as an isodicentric chromosome; i.e. 2 copies of a specific part of the long arm of chromosome 15 (most commonly, 15q11-q13) that is mirrored and doubled, with 2 centromere
Centromere
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come closest in contact. It is involved in cell division as the point of mitotic spindle attachment...
s and 2 DNA satellite
Satellite DNA
Satellite DNA consists of very large arrays of tandemly repeating, non-coding DNA. Satellite DNA is the main component of functional centromeres, and form the main structural constituent of heterochromatin....
s. The smallest markers appear to be harmless and they may go undetected. However, if they are large enough to contain a number of important genes, they may result in "idic(15) syndrome" which is characterized by mental retardation, autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and other neurological symptoms. One of the regions responsible for the symptoms of idic(15)syndrome is the critical PWS/AS-region named after the Prader-Willi and/or Angelman syndromes.
Diagnosis/Testing
The extra chromosome in people with idic(15) can be easily detected through chromosome analysis (karyotyping). Additional tests are usually required. FISH (Fluorescent in situ hybridizationFluorescent in situ hybridization
FISH is a cytogenetic technique developed by biomedical researchers in the early 1980s that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH uses fluorescent probes that bind to only those parts of the chromosome with which they show a high...
) is used to confirm the diagnosis by distinguishing idic(15) from other supernumerary marker chromosomes. Array CGH could be used to determine the gene content and dosage so that clinical picture could be foreseen.
Interstitial duplications of chromosome 15 can be more difficult to detect on a routine chromosome analysis but are clearly identifiable using a 15q FISH study. Families should always discuss the results of chromosome and FISH studies with a genetic counselor or other genetics professionals to ensure accurate interpretation.
Isodicentric chromosome 15 and autism
For more than 12 years, scientists have noticed that some individuals with autism also have idic(15). In fact, idic(15) is the most frequently identified chromosome problem in individuals with autismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
. (A chromosome anomaly involves extra or missing chromosomal material, not changes within the genes such as Fragile X syndrome
Fragile X syndrome
Fragile X syndrome , Martin–Bell syndrome, or Escalante's syndrome , is a genetic syndrome that is the most commonly known single-gene cause of autism and the most common inherited cause of intellectual disability...
). It is suggested that the co-occurrence of autism and idic(15) is not by chance. There may be a gene or genes in the 15q11-q13 region that is/are related to the development of autism in some individuals.
Genetic research studies of individuals without chromosome anomalies also support this idea that an autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
-related gene may be present in 15q11-q13. Specifically, research studies found that certain DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
markers from the 15q11-q13 region were found more often in individuals with autism than in individuals without autism. Although these DNA markers are too small to be genes, they suggest that researchers may be getting close to finding an autism gene in this region.
Prognosis/Management
At the present time, there is no specific treatment that can undo any chromosomal abnormality, nor the genetic pattern seen in people with idic(15). The extra chromosomal material in those affected was present at or shortly after conception, and its effects on brain development began taking place long before the child was born. Therapies are available to help address many of the symptoms associated with idic(15). Physical, occupational, and speech therapies along with special education techniques can stimulate children with idic(15) to develop to their full potential.In terms of medical management of the symptoms associated with dup15q syndrome, families should be aware that individuals with chromosome 15 duplications may tolerate medications differently and may be more sensitive to side effects for some classes of medications, such as the serotonin reuptake inhibitor type medications (SSRI).
Thus, these should be used with caution and any new medication should be instituted in a controlled setting, with slow titration of levels and with a clear endpoint as to what the expected outcome for treatment is.
Genetic Counseling
In general, idic(15) occurs de novoDe novo
In general usage, de novo is a Latin expression meaning "from the beginning," "afresh," "anew," "beginning again." It is used in:* De novo transcriptome assembly, the method of creating a transcriptome without a reference genome...
but the parents must be karyotyped to make sure it is not inherited, mostly because this will affect the course of genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
given to the family. If the abnormality is found prenatally and one of the parents harbour the marker, the child has a chance of being normal. Further tests should however be done to prove the marker has not been rearranged while being inherited. This information is also necessary for counseling of future pregnancies. Each family is unique and should therefore be handled individually.
External links
- IDEAS is a non-profit organization providing family support and awareness, research and targeted treatments for chromosome 15q duplication syndrome.
- Unique is a UK based source of information and support to families and individuals affected by any rare chromosome disorder and to the professionals who work with them.