Jacobsen syndrome

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Jacobsen syndrome
Other namesDel(11)(qter), distal deletion 11q, distal monosomy 11q, monosomy 11qter
Jacobsen syndrome patient.JPG
A girl displaying characteristic facial features of Jacobsen syndrome
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg

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. [1] The deletion may range from 5 million to 16 million deleted DNA base pairs. [2] The severity of symptoms depends on the number of deletions; the more deletions there are, the more severe the symptoms are likely to be.

Contents

People with Jacobsen syndrome have serious intellectual disabilities, dysmorphic features, delayed development and a variety of physical problems including heart defects. Research shows that almost 88.5% of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. [3]

Jacobsen syndrome is catastrophic in 1 out of every 5 cases, with children usually dying within the first 2 years of life due to heart complications. [4]

Signs and symptoms

Almost all children with Jacobsen syndrome have intellectual disabilities, which range from mild to moderate depending upon the number of the deletions of genes from the chromosome. [5] Most have delayed development, including delayed speech, motor disabilities and lack of coordination, which makes simple activities like sitting, standing and walking difficult. Most children eventually start speaking, but in cases with severe intellectual disability language use is highly restricted. [6]

They have distinctive facial features like:

Some children also experience behavioural problems like distractibility, hyperactivity, impaired communication and social skills, which qualifies them for a diagnosis of ASD and ADHD. [8] Heart defects are very common in children with Jacobsen syndrome. 88.5% of people with the disorder have Paris-Trousseau syndrome, which is a bleeding disorder and causes a lifelong risk of abnormal bleeding and bruising due to dysfunction in the platelets. [9] Other symptoms may include eye problems, ear and sinus infections, hearing problems, bone deformities, growth hormone deficiency, gastrointestinal problems, kidney malfunctions, etc. [10]

Cause

Jacobsen syndrome is caused by deletion of genetic material from the long arm of chromosome 11. The size of deletion may vary across patients, but the deletion always occurs at the end terminal of the q arm of chromosome 11. [11] There are three ways in which the deletion could occur:

de novo deletion- this is a random event that occurred during the formation of the sperm or the egg or during the cell division in the embryonic stage, where genes from chromosome 11 get deleted. [12]

Imbalanced translocation- in this case, a parent with balanced translocation or other types of chromosomal rearrangement can pass on these genes to their children which further results in an imbalanced translocation. The affected children have deletions on chromosome 11 as well as some extra genetic material from another chromosome. [13]

Ring chromosome 11- in this case genetic material from both long and short arm of the chromosome get deleted, and the remaining part joins and forms a ring like structure. Here the affected person would have symptoms associated with both 11q and 11p deletion. [14]

Genetics

If de novo deletion occurs then both the parents have normal chromosomes, and chances that another child will have the deletion decline. Very few cases have been found in which the deletion has been present in mosaic form (where some of the cells have deletion on chromosome 11 and some do not, and the symptoms are less severe) in one of the parents, which increases the risk of having another child with Jacobsen syndrome. When the child's chromosomal abnormality occurs due to one of the parents' balanced translocation, the chances of another child having the abnormality is high. [15]

Diagnosis

Diagnosing Jacobsen syndrome can be difficult in some cases because it is a rare chromosomal disorder. [16] There are a variety of tests that can be carried out, like karyotypes, cardiac echocardiograms, a renal sonogram, a platelet count, blood counts, a brain imaging study. [17] Genetic testing can be carried out for diagnosis. Here chromosomes are stained to give a barcode like appearance and studied under the microscope, which reveals the broken and deleted genes. The condition can also be diagnosed early in the prenatal stage if there are any abnormalities seen in the ultrasound. [18] A simple assessment of the symptoms can be done to diagnose the syndrome. A thorough physical examination could be carried out to assess the symptoms. [19]

Treatment

There has been no treatment discovered for Jacobsen syndrome to date, but the symptoms can be treated. 56% of children with Jacobsen syndrome have congenital heart problems; to keep them in check, a baseline evaluation can be made by a paediatric cardiologist by carrying out an electrocardiogram or echocardiogram. Any problems that are found can be treated then.[ citation needed ]

Monthly CBT may help ease bleeding disorders. Consecutively, platelet transfusion and ddAVP can be carried out. Medication that interferes with platelet count should be avoided, and oral contraceptive therapy may be considered for women with heavy bleeding during menses.[ citation needed ]

An evaluation by a neuropsychologist or a behaviour specialist like a psychiatrist or psychologist can be performed, including brain imaging like MRI or ERP. Later, as deemed appropriate, intervention programs can be carried through. Music therapy is very beneficial for language development. According to the age, vision and hearing tests can aid in fixing problems related cognition. [20] For problems related to behaviour like ADHD, medication or therapy would be required but a combination of both is more effective. [21] An ophthalmologist should be consulted to treat the eye defects. Play and interactive games encourage the child to speak. Habilitiation in children should begin at an early age. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. The entire family is supported to help the affected children and their families adjust better. [22]

Prevalence

The estimated prevalence of Jacobsen syndrome is believed to be approximately 1 out of every 100,000 births. For reasons unknown, females are twice as likely to have Jacobsen syndrome than males. No preference for any race or ethnicity has been reported so far. [23]

History

The syndrome was first identified by Danish geneticist Petrea Jacobsen in 1973 and was named after her. She discovered it in a family where multiple people had the disorder, and found that the affected children had unbalanced translocation between chromosome 11 and 21 which they had inherited from one of their parents who had balanced translocation. Since then, only 200 cases have been reported of Jacobsen syndrome in medical literature. [24]

Related Research Articles

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<span class="mw-page-title-main">Miller–Dieker syndrome</span> Medical condition

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.

<span class="mw-page-title-main">Noonan syndrome</span> Genetic condition involving facial, heart, blood and skeletal features

Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored eyes, low-set ears, a short neck, and a small lower jaw. Heart problems may include pulmonary valve stenosis. The breast bone may either protrude or be sunken, while the spine may be abnormally curved. Intelligence in the syndrome is often normal. Complications of NS can include leukemia.

<span class="mw-page-title-main">Cri du chat syndrome</span> Human medical condition

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Smith–Magenis Syndrome (SMS), also known as 17p- syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome 17. It has features including intellectual disability, facial abnormalities, difficulty sleeping, and numerous behavioral problems such as self-harm. Smith–Magenis syndrome affects an estimated between 1 in 15,000 to 1 in 25,000 individuals.

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<span class="mw-page-title-main">Greig cephalopolysyndactyly syndrome</span> Medical condition

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<span class="mw-page-title-main">22q13 deletion syndrome</span> 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.

<span class="mw-page-title-main">1p36 deletion syndrome</span> Medical condition

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<span class="mw-page-title-main">Trisomy 22</span> Medical condition

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<span class="mw-page-title-main">13q deletion syndrome</span> Medical condition

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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.

<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, intellectual disability and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves' disease.

References

  1. ↑ Reference, Genetics Home. "Jacobsensyndrome". Genetics Home Reference.
  2. ↑ "Jacobsen Syndrome". prezi.com.
  3. ↑ Favier, Remi; Akshoomoff, Natacha; Mattson, Sarah; Grossfeld, Paul (1 September 2015). "Jacobsen syndrome: Advances in our knowledge of phenotype and genotype". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 169 (3): 239–250. doi:10.1002/ajmg.c.31448. PMID   26285164. S2CID   10194565.
  4. ↑ "Jacobsen Syndrome". DoveMed.
  5. ↑ "11q deletion syndrome". www.socialstyrelsen.se (in Swedish). Archived from the original on 2019-02-26. Retrieved 2017-11-27.
  6. ↑ "Jacobsen Syndrome". DoveMed.
  7. ↑ Reference, Genetics Home. "Jacobsen syndrome". Genetics Home Reference.
  8. ↑ "11q deletion syndrome". www.socialstyrelsen.se (in Swedish). Archived from the original on 2019-02-26. Retrieved 2017-11-27.
  9. ↑ Favier, Remi; Akshoomoff, Natacha; Mattson, Sarah; Grossfeld, Paul (1 September 2015). "Jacobsen syndrome: Advances in our knowledge of phenotype and genotype". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 169 (3): 239–250. doi:10.1002/ajmg.c.31448. PMID   26285164. S2CID   10194565.
  10. ↑ "Jacobsen Syndrome". DoveMed.
  11. ↑ "11q deletion syndrome". www.socialstyrelsen.se (in Swedish). Archived from the original on 2019-02-26. Retrieved 2017-11-27.
  12. ↑ "Jacobsen syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov.
  13. ↑ "Jacobsen syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov.
  14. ↑ "11q deletion syndrome". www.socialstyrelsen.se (in Swedish). Archived from the original on 2019-02-26. Retrieved 2017-11-27.
  15. ↑ "11q deletion syndrome". www.socialstyrelsen.se (in Swedish). Archived from the original on 2019-02-26. Retrieved 2017-11-27.
  16. ↑ "Jacobsen Syndrome". Healthline. 2016-11-28.
  17. ↑ "Jacobsen Syndrome". prezi.com.
  18. ↑ "Jacobsen Syndrome". Healthline. 2016-11-28.
  19. ↑ "Jacobsen Syndrome". prezi.com.
  20. ↑ Reference, Genetics Home. "Jacobsen syndrome". Genetics Home Reference.
  21. ↑ "Treatment". nhs.uk. June 2018.
  22. ↑ "11q deletion syndrome". www.socialstyrelsen.se (in Swedish). Archived from the original on 2019-02-26. Retrieved 2017-11-27.
  23. ↑ "Jacobsen Syndrome". DoveMed.
  24. ↑ Favier, Remi; Akshoomoff, Natacha; Mattson, Sarah; Grossfeld, Paul (1 September 2015). "Jacobsen syndrome: Advances in our knowledge of phenotype and genotype". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 169 (3): 239–250. doi:10.1002/ajmg.c.31448. PMID   26285164. S2CID   10194565.
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