Ring chromosome 15

Last updated
Ring chromosome 15
Other namesRing chromosome 15 syndrome, Ring 15
NLM ring chromosome.jpg
Diagram of the formation of a ring chromosome
Specialty Medical genetics
DurationLifelong
CausesDeletion of genetic information from chromosome 15
Treatment Supportive
FrequencyRare

Ring chromosome 15 (sometimes denoted as r15) is a condition that arises when chromosome 15 fuses to form a ring chromosome. Usually, ring chromosome 15 forms due to the modification or deletion of genetic information on chromosome 15 in the preliminary stages of embryonic development, but it can rarely also be inherited. [1]

Contents

All chromosomes have the capacity to form ring chromosomes. The symptoms and severity largely depend on the amount and location of the genetic information lost. [2] If the ends of the chromosome fuse with no loss of genetic material, the individual retains the normal phenotype with relatively slight differences. However, evidence suggests that when there is deletion of genetic information at the distal unstable ends where the subtelomeric structures fuse, syndromes associated with that particular chromosome arise. [3]

Treatment for ring chromosome 15 predominantly targets the management of these symptoms rather than the chromosome ring itself.

Presentation

Cafe au lait spots Cafe au lait.jpg
Café au lait spots

Reported cases are few in number, and the phenotype expression for ring chromosome 15 syndrome occurs over a wide spectrum. [4] [5] [6] As well, the cells of patients can have different levels of mosaicism, creating even greater variation in the presence and severity of expression. [2] Thus, while a precise genotype–phenotype association hasn't been fully established, [2] common features associated with the syndrome have been determined.

An examination of 25 cases showed that growth deficiency (present in 100% of reviewed cases), some degree of intellectual disability (95%), and microcephaly (88%) are the most common developments. [4] Other less frequent symptoms include delayed bone age (75%), hypertelorism (46%), brachydactyly (44%), triangular face (42%), speech delay (39%), frontal bossing (36%), anomalous ear (30%), café au lait spots (30%), cryptorchidism (30%) and cardiac abnormalities (30%). [4]

Research into ring chromosome 15 generally attempts to elucidate the causes of symptoms. For example, growth retardation may be caused by terminal deletion of the region 15q26, [7] leading to insulin–like growth factor I resistance. [8] [9]

Mechanism

The human body stores its genetic information in chromosomes. The number of chromosomes and the gene locus on the chromosome is unique to each species. Humans have 23 pairs of chromosomes, 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes that differentiate between males and females. [10] All human chromosomes have 2 arms – the p (short) and the q (long) arm, which are separated by the centromeres. [11]

Telomeric ends Telomere.png
Telomeric ends

There are two proposed mechanisms of forming the ring chromosome. One suggests that chromosome 15 undergoes distortion on both p and q arms prior to the fusion of two broken arms, resulting in great loss of genetic materials. Therefore, the patients of this type of ring chromosome 15 display severe clinical features. [12]

The other proposed mechanism suggests the direct fusion of two telomeres without losing any of the telomeric and subtelomeric sequences. Consequently, most of the genetic material is conserved and symptoms are expressed in a milder form, making diagnosis more difficult. [13]

Diagnosis

Congenital diaphragmatic hernia Diaphragm hernia2.jpg
Congenital diaphragmatic hernia

In most cases, postnatal diagnosis is done and up to 2011, only four cases are reported via prenatal diagnosis. [3] Congenital diaphragmatic hernia and intrauterine growth retardation (these two signs put the patients at the risk of afflicting with ring chromosome 15) by fetal ultrasound (Obstetric ultrasonography) at the time period of 16–24 weeks, further investigation and diagnostics (such as karyotyping) must be performed to test the possibility of ring chromosome 15.[ citation needed ]

Postnatal diagnosis

Patients could be considered to have ring chromosome 15 if they are found with: growth deficiency, [3] café au lait spots, bone age delay, and simian crease or other dysmorphic features after birth.[ citation needed ]

Management

Treatment of the disease is based on alleviating symptoms, [1] commonly including physiotherapy, occupational therapy, and speech and language therapy. [14] In addition, case reports have found that recombinant human growth hormone treatment may be beneficial for improving the growth velocity of patients with short stature. [3] [4] [15]

Epidemiology

Ring chromosome syndromes are rare congenital disorders that are likely to occur in both males and females, and the symptoms can be observed from birth since it arises during the embryonic stage. All races and ethnicities are prone to the disorders and the risk can be higher if the parents are carriers since it is genetically inherited.[ citation needed ]

Any of the 23 pairs of chromosomes can be ringed, and a recent study conducted by the 'Human Ring Chromosome Registry' in China revealed that the more frequent forms of ring chromosomes reported were 13, 15, 18, and 22. [16]

History

Ring chromosome 15 is an uncommon genetic disorder first noted by Dr. Petrea Jacobsen in 1966. [17] As of 2005, less than 50 cases have been reported. [2]

Related Research Articles

Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become constantly hungry, which often leads to obesity and type 2 diabetes. Mild to moderate intellectual impairment and behavioral problems are also typical of the disorder. Often, affected individuals have a narrow forehead, small hands and feet, short height, and light skin and hair. Most are unable to have children.

Jacobsen syndrome Medical condition

Jacobsen syndrome is a rare chromosomal disorder resulting from deletion of genes from chromosome 11 that includes band 11q24.1. It is a congenital disorder. Since the deletion takes place on the q arm of chromosome 11, it is also called 11q terminal deletion disorder. The deletion may range from 5 million to 16 million deleted DNA base pairs. The severity of symptoms depends on the number of deletions; the more deletions there are, the more severe the symptoms are likely to be.

Ring chromosome Chromosome whose ends have fused together to form a ring

A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring. Ring chromosomes were first discovered by Lilian Vaughan Morgan in 1926. A ring chromosome is denoted by the symbol r in human genetics and R in Drosophila genetics. Ring chromosomes may form in cells following genetic damage by mutagens like radiation, but they may also arise spontaneously during development.

<span class="mw-page-title-main">DiGeorge syndrome</span> Condition caused by a microdeletion on the long arm of chromosome 22

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent infections, developmental delay, learning problems and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves' disease.

GAPO syndrome Medical condition

GAPO syndrome is a rare, autosomal recessive disorder that causes severe growth retardation, and has been observed fewer than 30 times before 2011. GAPO is an acronym that encompasses the predominant traits of the disorder: growth retardation, alopecia, pseudoanodontia, and worsening optic atrophy in some subjects. Other common symptoms include premature aging, large, prominent foreheads, and delayed bone aging. GAPO syndrome typically results in premature death around age 30–40, due to interstitial fibrosis and atherosclerosis.

22q13 deletion syndrome Rare genetic syndrome

22q13 deletion syndrome, also known as Phelan–McDermid syndrome (PMS), is a genetic disorder caused by deletions or rearrangements on the q terminal end of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by SHANK3 mutations, a definition that appears to exclude terminal deletions. The requirement to include SHANK3 in the definition is supported by many but not by those who first described 22q13 deletion syndrome.

Rabson–Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance. The disorder is caused by mutations in the insulin receptor gene. Symptoms include growth abnormalities of the head, face and nails, along with the development of acanthosis nigricans. Treatment involves controlling blood glucose levels by using insulin and incorporating a strategically planned, controlled diet. Also, direct actions against other symptoms may be taken This syndrome usually affects children and has a prognosis of 1–2 years.

Lujan–Fryns syndrome Medical condition

Lujan–Fryns syndrome (LFS) is an X-linked genetic disorder that causes mild to moderate intellectual disability and features described as Marfanoid habitus, referring to a group of physical characteristics similar to those found in Marfan syndrome. These features include a tall, thin stature and long, slender limbs. LFS is also associated with psychopathology and behavioral abnormalities, and it exhibits a number of malformations affecting the brain and heart. The disorder is inherited in an X-linked dominant manner, and is attributed to a missense mutation in the MED12 gene. There is currently no treatment or therapy for the underlying MED12 malfunction, and the exact cause of the disorder remains unclear.

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Silver–Russell syndrome Medical condition

Silver–Russell syndrome (SRS), also called Silver–Russell dwarfism, is a rare congenital growth disorder. In the United States it is usually referred to as Russell–Silver syndrome (RSS), and Silver–Russell syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism.

DECIPHER is a web-based resource and database of genomic variation data from analysis of patient DNA. It documents submicroscopic chromosome abnormalities and pathogenic sequence variants, from over 25000 patients and maps them to the human genome using Ensembl or UCSC Genome Browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndromes, together with links to relevant scientific reports and support groups.

1q21.1 deletion syndrome is a rare aberration of chromosome 1. A human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome, one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. One chromosome has the normal length and the other is too short.

9q34 deletion syndrome is a rare genetic disorder. Terminal deletions of chromosome 9q34 have been associated with childhood hypotonia, a distinctive facial appearance and developmental disability. The facial features typically described include arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip. Individuals with this disease may often have speech impediments, such as speech delays. Other characteristics of this disease include: epilepsy, congenital and urogenital defects, microcephaly, corpulence, and psychiatric disorders. From analysis of chromosomal breakpoints, as well as gene sequencing in suggestive cases, Kleefstra and colleagues identified EHMT1 as the causative gene. This gene is responsible for producing the protein histone methyltransferase which functions to alter histones. Ultimately, histone methyltransferases are important in deactivating certain genes, needed for proper growth and development. Moreover, a frameshift, missense, or nonsense error in the coding sequence of EHMT1 can result in this condition in an individual.

Chromosomal deletion syndrome Medical condition

Chromosomal deletion syndromes result from deletion of parts of chromosomes. Depending on the location, size, and whom the deletion is inherited from, there are a few known different variations of chromosome deletions. Chromosomal deletion syndromes typically involve larger deletions that are visible using karyotyping techniques. Smaller deletions result in Microdeletion syndrome, which are detected using fluorescence in situ hybridization (FISH)

Wieacker syndrome Medical condition

First being described and identified in 1985, Wieacker-Wolff syndrome is a rare, slowly progressive, genetic disorder present at birth and characterized by deformities of the joints of the feet, muscle degeneration, mild intellectual disability and an impaired ability to move certain muscles of the eyes, face and tongue. Wieacker syndrome is inherited as an X-linked recessive trait.

Waardenburg Syndrome Type 4A is an extremely rare congenital disorder caused by a mutation in an endothelin receptor gene. It results in common Waardenburg syndrome symptoms such as abnormal hair and skin pigmentation and heterochromia, but also present with symptoms of Hirschsprung’s disease. Symptoms include abdominal pain and bowel obstruction. Waardenburg Syndrome Type 4A is the rarest among the types, appearing only once in about every 1,000,000 individuals. There have only been a total of 50 cases reported in total as of 2016.

<span class="mw-page-title-main">17q12 microdeletion syndrome</span> Rare genetic anomaly in humans

17q12 microdeletion syndrome, also known as 17q12 deletion syndrome, is a rare chromosomal anomaly caused by the deletion of a small amount of material from a region in the long arm of chromosome 17. It is typified by deletion of the HNF1B gene, resulting in kidney abnormalities and renal cysts and diabetes syndrome. It also has neurocognitive effects, and has been implicated as a genetic factor for autism and schizophrenia.

<span class="mw-page-title-main">Ring chromosome 22</span> Rare chromosomal disorder

Ring chromosome 22, also known as ring 22, is a rare chromosomal disorder. Ring chromosomes occur when the ends of a chromosome lose material and fuse into a ring shape; in the case of ring 22, this occurs for chromosome 22, the last numbered human autosome. Ring chromosome 22 is marked by a number of consistent traits, such as intellectual disability, speech delay, hypotonia, and hyperactivity. The condition has a similar phenotype to Phelan-McDermid syndrome, as the loss of the SHANK3 gene is implicated in both.

Filippi syndrome, also known as Syndactyly Type I with Microcephaly and Mental Retardation, is a very rare autosomal recessive genetic disease. Only a very limited number of cases have been reported to date. Filippi Syndrome is associated with diverse symptoms of varying severity across affected individuals, for example malformation of digits, craniofacial abnormalities, intellectual disability, and growth retardation. The diagnosis of Filippi Syndrome can be done through clinical observation, radiography, and genetic testing. Filippi Syndrome cannot be cured directly as of current, hence the main focus of treatments is on tackling the symptoms observed on affected individuals. It was first reported in 1985.

Otofaciocervical syndrome Medical condition

Otofaciocervical syndrome, also known as Fara Chlupackova syndrome, are a small group of rare developmental disorders of genetic origin which are characterized by facial dysmorphisms, long neck, preauricular and/or branchial pits, cervical muscle hypoplasia, hearing loss, and mild intellectual disabilities. Additional findings include vertebral anomalies and short stature.

References

  1. 1 2 "Ring chromosome 15 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2019-04-11.
  2. 1 2 3 4 Glass, Ian A.; Rauen, Katherine A.; Chen, Emily; Parkes, Jillian; Alberston, Donna G.; Pinkel, Daniel; Cotter, Philip D. (2005-11-03). "Ring chromosome 15: characterization by array CGH". Human Genetics. 118 (5): 611–617. doi:10.1007/s00439-005-0030-z. ISSN   0340-6717. PMID   16267671. S2CID   24115238.
  3. 1 2 3 4 Xu, F; Zou, CC; Liang, L; Huang, XM; Shao, YN (2011). "Ring Chromosome 15 Syndrome:Case Report and Literature Review". HK J Paediatr. New Series: 175–179.
  4. 1 2 3 4 Butler, Merlin G.; Fogo, Agnes B.; Fuchs, David A.; Collins, Francis S.; Dev, Viathilingam G.; Phillips, John A.; Optiz, John M.; Reynolds, James F. (Jan 1988). "Two patients with ring chromosome 15 syndrome". American Journal of Medical Genetics. 29 (1): 149–154. doi:10.1002/ajmg.1320290119. ISSN   0148-7299. PMC   5083070 . PMID   3278612.
  5. ↑ Roback, Ellen W.; Barakat, Amin J.; Dev, V. G.; Mbikay, Majambu; Chrétien, Michel; Butler, Merlin G. (1991-01-01). "An infant with deletion of the distal long arm of chromosome 15 (q26.1→qter) and loss of insulin-like growth factor 1 receptor gene". American Journal of Medical Genetics. 38 (1): 74–79. doi:10.1002/ajmg.1320380117. ISSN   0148-7299. PMC   5493390 . PMID   1849352.
  6. ↑ Nuutinen, M; Kouvalainen, K; Knip, M (1995-06-01). "Good growth response to growth hormone treatment in the ring chromosome 15 syndrome". Journal of Medical Genetics. 32 (6): 486–487. doi:10.1136/jmg.32.6.486. ISSN   1468-6244. PMC   1050492 . PMID   7545237.
  7. ↑ Harada, N; Shimokawa, O; Nagai, T; Kato, R; Kondoh, T; Niikawa, N; Matsumoto, N (2002-10-08). "A 4-Mb critical region for intrauterine growth retardation at 15q26". Clinical Genetics. 62 (4): 340–342. doi:10.1034/j.1399-0004.2002.620416.x. ISSN   0009-9163. PMID   12372065. S2CID   35310940.
  8. ↑ "Orphanet: Growth%20delay%20due%20to%20insulin like%20growth%20factor%20I%20resistance". www.orpha.net. Retrieved 23 April 2020.
  9. ↑ Peoples, R.; Milatovich, A.; Francke, U. (1995). "Hemizygosity at the insulin-like growth factor I eceptor (IGF1R) locus and growth failure in the ring chromosome 15 syndrome". Cytogenetic and Genome Research. 70 (3–4): 228–234. doi:10.1159/000134040. ISSN   1424-859X. PMID   7789178.
  10. ↑ Reference, Genetics Home. "What is a chromosome?". Genetics Home Reference. Retrieved 2019-04-11.
  11. ↑ "Definition of Long arm of a chromosome". MedicineNet. Retrieved 2019-04-11.
  12. ↑ Kosztolanyi, G (Feb 1987). "Does "ring syndrome" exist? An analysis of 207 case reports on patients with a ring autosome". Human Genetics. 75 (2): 174–179. doi:10.1007/bf00591082. ISSN   0340-6717. PMID   3817812. S2CID   1596675.
  13. ↑ Pezzolo, Annalisa; Gimelli, Giorgio; Cohen, Amnon; Lavaggetto, Antonella; Romano, Cesare; Fogu, Giuseppina; Zuffardi, Orsetta (Aug 1993). "Presence of telomeric and subtelomeric sequences at the fusion points of ring chromosomes indicates that the ring syndrome is caused by ring instability". Human Genetics. 92 (1): 23–27. doi:10.1007/bf00216140. ISSN   0340-6717. PMID   8365723. S2CID   23582495.
  14. ↑ Morava, E. (2005). "Ring 15" (PDF). Unique. Archived from the original (PDF) on 5 December 2017.
  15. ↑ Chen, Meiping; Ke, Xiaoan; Liang, Hanting; Gong, Fengying; Yang, Hongbo; Wang, Linjie; Duan, Lian; Pan, Hui; Cao, Dongyan; Zhu, Huijuan (December 2021). "The phenotype and rhGH treatment response of ring Chromosome 15 Syndrome: Case report and literature review". Molecular Genetics & Genomic Medicine. 9 (12): e1842. doi:10.1002/mgg3.1842. ISSN   2324-9269. PMC   8683626 . PMID   34747577.
  16. ↑ Hu, Qiping; Chai, Hongyan; Shu, Wei; Li, Peining (2018-02-27). "Human ring chromosome registry for cases in the Chinese population: re-emphasizing Cytogenomic and clinical heterogeneity and reviewing diagnostic and treatment strategies". Molecular Cytogenetics. 11 (1): 19. doi: 10.1186/s13039-018-0367-3 . ISSN   1755-8166. PMC   5828142 . PMID   29492108.
  17. ↑ JACOBSEN, PETREA (2009-09-02). "A Ring Chromosome in the 13-15 Group Associated with Microcephalic Dwarfism, Mental Retardation and Emotional Immaturity". Hereditas. 55 (2–3): 188–191. doi: 10.1111/j.1601-5223.1966.tb02047.x . ISSN   0018-0661.
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