13q deletion syndrome is inherited in an autosomal dominant manner
13q deletion syndrome is a rare genetic disease caused by the deletion of some or all of the large arm of human chromosome 13. Depending upon the size and location of the deletion on chromosome 13, the physical and mental manifestations will vary. It has the potential to cause intellectual disability and congenital malformations that affect a variety of organ systems. Because of the rarity of the disease in addition to the variations in the disease, the specific genes that cause this disease are unknown.[1] This disease is also known as:
Partial Monosomy of the Long Arm of Chromosome 13 [2]
Signs and symptoms
Variations of the signs and symptoms occur depending upon the area of chromosome 13 that is deleted. Deletions from the centromere to 13q32 or any deletions including the 13q32 band are associated with slow growth, intellectual disability, and congenital malformations. Deletions from 13q33 to the end of the chromosome are associated with intellectual disability. Intellectual disabilities range from very mild to very severe, and can co-occur with behavioral disorders and/or autism spectrum disorders.[3]
Other skeletal malformations are found with 13q deletion syndrome, including syndactyly, clubfoot, clinodactyly, and malformations of the vertebrae and/or thumbs.[3]
Deletions that include the 13q32 band, which contains the brain development gene ZIC2, are associated with holoprosencephaly; they are also associated with hand and foot malformations. Deletions that include the 13q14 band, which contains the tumor suppressor geneRb, are associated with a higher risk of developing retinoblastoma, which is more common in XY children. Deletion of the 13q33.3 band is associated with hypospadias.[3] Other genes in the potentially affected region include NUFIP1, HTR2A, PDCH8, and PCDH17.[4]
In males with 13q deletion syndrome, genital abnormalities are common. The meatus, or urinary opening, may appear on the underside of the penis (hypospadis), and/or the testes will not descend into the scrotum (cryptochidism). The scrotum will often be unusually small or abnormally divided into two sections (bifid scrotum); the penis may be unusually small (micropenis), and/or abnormal passage may be present between the scrotum and the anus (perineal fistula). In rare cases, the anal opening may be absent or covered by a thing membrane which can cause obstruction (anal atresia).[2]
Causes
Although one can inherit 13q deletion syndrome, the most common way to obtain the disease is through genetic mutations. All human chromosomes have 2 arms, the p (short) arm and the q (long) arm. They are separated from each other only by a primary constriction, the centromere, the point at which the chromosome is attached to the spindle during cell division.[5] When portions of the long arm of chromosome 13 are altered during gametogenesis, 13q deletion syndrome results. Because the 13th chromosome holds between 300 and 400 genes, a deletion of any part of this chromosome (locus (genetics)) or mutation of any codon can lead to a large variety of malfunctions within the system.[citation needed]
Mechanism
This disorder is caused by the deletion of the long arm of chromosome 13, which can either be deleted linearly or as a ring chromosome. It is typically not hereditary— the loss of a portion of the chromosome typically occurs during gametogenesis, making it a de novo mutation. When it is hereditary, it is usually caused by a parent having mosaicism or a balanced translocation.[3] The severity of the disorder is correlated with the size of the deletion, with larger deletions causing more severe manifestations.[3] There are three common anomalies predominately observed in 13q deletion syndrome: congenital heart disease, anorectal/genitourinary, and gastrointestinal tract malformations. These are all part of the VACTERL associations which is a disorder that is characterized by vertebral anomalies, anal atresia, cardiac defect, tracheoesphageal fistula, renal anomalies, and limb defects.[1]
Diagnosis
13q deletion syndrome can only be definitively diagnosed by genetic analysis, which can be done prenatally or after birth.[3] Family and medical history is important when diagnosing a child with 13q deletion syndrome. Chromosome testing of both parents can provide more information on whether or not the deletion was inherited.[2] Increased nuchal translucency in a first-trimester ultrasound may indicate the presence of 13q deletion.[6] It is important to follow through with genetic testing because there are many other diseases that have similar clinical manifestations of 13q deletion syndrome.[2] Special imaging tests, enzyme assays, electrocardiogram (ECG), echocardiogram, cardiac catheterization and more can be run on a patient who has 13q deletion syndrome in order to diagnose their accompanying defects.[citation needed]
Treatment
Although there is no cure for 13q deletion syndrome, symptoms can be managed, usually with the involvement of a neurologist, rehabilitation physician, occupational therapist, physiotherapist, psychotherapist, nutritionist, special education professional, and/or speech therapist. No treatment for 13q deletion syndrome will ever be identical due to the variations in the disease which is why the use of personalized teams with members from different medical fields is vital to the patient. If the affected child's growth is particularly slow, growth hormone treatment can be used to augment growth. Plastic surgeries can repair cleft palates, and surgical repair or monitoring by a pediatric cardiologist can manage cardiac defects. Some skeletal, neurological, genitourinary, gastrointestinal, and ophthalmic abnormalities can be definitively treated with surgery. Endocrine abnormalities can often be managed medically. Even if a child is responding to well to their medical treatment, it is important to utilize special educators, speech and occupational therapists, and physiotherapists to help the child develop skills that will aid in their life in and out of the classroom.[3]
Prognosis
Affected individuals may have a somewhat shortened lifespan without treatment. The maximum lifespan without treatment is 67 years. When a 13q deletion is detected, such as in a bone marrow biopsy for Multiple Myeloma, chemo treatments in recent years have the ability to extend life expectancy without limitations depending on response to treatments. It is not uncommon for adults with 13q deletion syndrome to need support services to maintain their activities of daily living, including adult day care services or housing services.[3]
Epidemiology
It is incredibly rare, with fewer than 190 cases described.[3] Although rare, deletions involving chromosome 13q are among the most commonly observed monosomies[2] Chromosome 13, Partial Monosomy 13q appears to affect females slightly more frequently than males. Since the disorder was originally reported in 1963, more than 125 cases have been recorded in the medical literature.[2] The age of onset can vary from patient to patient because of the differences in deletions. For example, a study was able to demonstrate for the first time that a patient with a hemangioendothelioma of the liver with a simultaneous deletion in chromosome 13q of 28Mb did not develop Rb until the age of 3 years [7] while other patients with similar deletions have immediate clinical manifestations upon birth.
Research
As previously stated, partial deletions on the long arm of chromosome 13 can cause numerous different effects. These effects are due to the size and position of the deleted region. A recent study done in 2017 by Wang, Wang, Niu, and Cui looked at two patients with 13q terminal (13qter) deletion syndrome. The manifestation of these patients was anal atresia with rectoperineal fistula, complex type congenital heart disease, esophageal hiatus hernia with gastroesophageal reflux, facial anomalies and developmental and mental retardation. Using array comparative genomic hybridization, two regions were identified as deleted on 13q31-qter. These were 20.38 Mb in 13q31.3-qter and 12.99 Mb in 13q33.1-qter in patients 1 and 2, respectively. The authors were able to show that the gene encoding ephrin B2 (EFNB2) located in the 13q33.3-q34 region, and the gene coding for endothelin receptor type B, in the 13q22.1–31.3 region, may be suitable candidate genes for the observed urogenital/anorectal anomalies. In addition, the microRNA-17-92a-1 cluster host gene and the glypican 6 gene in the 13q31.3 region, as well as EFNB2 and the collagen type IV a1 chain (COL4A1) and COL4A2 genes in the 13q33.1-q34 region could possibly contribute to cardiovascular disease development together. The authors showed that it is possible that those genes may be involved in the pathogenesis of complex type congenital heart disease in patients with 13q deletion syndrome.[1] Unfortunately, there are no current clinical trials that are ongoing but research is continuing in search for clear connections between the clinical manifestations and the particular deletions that a patient has.[citation needed]
History
13q deletion syndrome was first described in 1963 and fully characterized in 1971.[3] There has not been much research done in the past with 13q deletion syndrome but more and more research is surfacing every year about the rare disease.[citation needed]
Related Research Articles
Prune belly syndrome is a rare, genetic birth defect affecting about 1 in 40,000 births. About 97% of those affected are male. Prune belly syndrome is a congenital disorder of the urinary system, characterized by a triad of symptoms. The syndrome is named for the mass of wrinkled skin that is often present on the abdomen of those with the disorder.
Miller–Dieker syndrome, Miller–Dieker lissencephaly syndrome (MDLS), and chromosome 17p13.3 deletion syndrome is a micro deletion syndrome characterized by congenital malformations. Congenital malformations are physical defects detectable in an infant at birth which can involve many different parts of the body including the brain, hearts, lungs, liver, bones, or intestinal tract. MDS is a contiguous gene syndrome – a disorder due to the deletion of multiple gene loci adjacent to one another. The disorder arises from the deletion of part of the small arm of chromosome 17p, leading to partial monosomy. There may be unbalanced translocations, or the presence of a ring chromosome 17.
Cri du chat syndrome is a rare genetic disorder due to a partial chromosome deletion on chromosome 5. Its name is a French term referring to the characteristic cat-like cry of affected children. It was first described by Jérôme Lejeune in 1963. The condition affects an estimated 1 in 50,000 live births across all ethnicities and is more common in females by a 4:3 ratio.
A coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is present during early stages of prenatal development, fails to close up completely before a child is born. Ocular coloboma is relatively uncommon, affecting less than one in every 10,000 births.
Atresia is a condition in which an orifice or passage in the body is closed or absent.
Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the development of the corpus callosum, the band of white matter connecting the two hemispheres in the brain, in the embryo is disrupted. The result of this is that the fibers that would otherwise form the corpus callosum are instead longitudinally oriented along the ipsilateral ventricular wall and form structures called Probst bundles.
Trisomy 8 causes Warkany syndrome 2, a human chromosomal disorder caused by having three copies (trisomy) of chromosome 8. It can appear with or without mosaicism.
Fraser syndrome is an autosomal recessive congenital disorder, identified by several developmental anomalies. Fraser syndrome is named for the geneticist George R. Fraser, who first described the syndrome in 1962.
Vaginal atresia is a condition in which the vagina is abnormally closed or absent. The main causes can either be complete vaginal hypoplasia, or a vaginal obstruction, often caused by an imperforate hymen or, less commonly, a transverse vaginal septum. It results in uterovaginal outflow tract obstruction. This condition does not usually occur by itself within an individual, but coupled with other developmental disorders within the female. The disorders that are usually coupled with a female who has vaginal atresia are Mayer-Rokitansky-Küster-Hauser syndrome, Bardet-Biedl syndrome, or Fraser syndrome. One out of every 5,000 women have this abnormality.
Aplasia is a birth defect where an organ or tissue is wholly or largely absent. It is caused by a defect in a developmental process.
Monosomy 9p is a rare chromosomal disorder in which some DNA is missing or has been deleted on the short arm region, "p", of one copy of chromosome 9 (9p22.2-p23). This deletion either happens de novo or as a result of a parent having the chromosome abnormality. This rare chromosomal abnormality is often diagnosed after birth when developmental delay, irregular facial features, structural irregularities within the heart, and genital defects are observed. Treatments for this syndrome usually focus on fixing the malformations that are commonly associated with it. The cause of the syndrome was first discovered in 1973, when an analysis of the chromosomes of three infants with similar clinical abnormalities revealed that they all had a partial deletion of the short arm of Chromosome 9. Symptoms include micro genitalia, intellectual disability with microcephaly and dysmorphic features.
Duane-radial ray syndrome, also known as Okihiro syndrome, is a rare autosomal dominant disorder that primarily affects the eyes and causes abnormalities of bones in the arms and hands. This disorder is considered to be a SALL4-related disorder due to the SALL4 gene mutations leading to these abnormalities. It is diagnosed by clinical findings on a physical exam as well as genetic testing and imaging. After being diagnosed, there are other evaluations that one may go through in order to determine the extent of the disease. There are various treatments for the symptoms of this disorder.
1p36 deletion syndrome is a congenital genetic disorder characterized by moderate to severe intellectual disability, delayed growth, hypotonia, seizures, limited speech ability, malformations, hearing and vision impairment, and distinct facial features. The symptoms may vary, depending on the exact location of the chromosomal deletion.
Ring chromosome 20, ring-shaped chromosome 20 or r(20) syndrome is a rare human chromosome abnormality where the two arms of chromosome 20 fuse to form a ring chromosome. The syndrome is associated with epileptic seizures, behaviour disorders and intellectual disability.
Young–Simpson syndrome (YSS) is a rare congenital disorder with symptoms including hypothyroidism, heart defects, facial dysmorphism, cryptorchidism in males, hypotonia, intellectual disability, and postnatal growth retardation.
Renal cysts and diabetes syndrome (RCAD), also known as MODY 5 or HNF1B-MODY, is a form of maturity onset diabetes of the young.
Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period. Fryns (1987) reviewed the syndrome.
Distal 18q- is a genetic condition caused by a deletion of genetic material within one of the two copies of chromosome 18. The deletion involves the distal section of 18q and typically extends to the tip of the long arm of chromosome 18.
Vaginal anomalies are abnormal structures that are formed during the prenatal development of the female reproductive system and are rare congenital defects that result in an abnormal or absent vagina.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
