• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report
Select language / seleccionar idioma:

Chromosome 11, Partial Monosomy 11q

Print

Last updated: 6/14/2023
Years published: 1989, 1996, 2001, 2009, 2012, 2015, 2018, 2023


Acknowledgment

NORD gratefully acknowledges Teresa Mattina, MD, Genetica Medica, Scientific Foundation and Clinic G.B. Morgagni, Catania, Italy (formerly Associate Professor in Medical genetics at the Biomedical Biotechnological Department, University of Catania) Catania, Italy, for assistance in the preparation of this report.


Disease Overview

Partial monosomy 11q syndrome is a rare chromosomal disorder in which a portion of the long arm of chromosome 11 is deleted (missing). Jacobsen syndrome is observed in SOME patients with 11q partial deletion. The region consistently missing in individuals with this disorder (JS) is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (this chromosome region is called the Jacobsen syndrome critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests (with or without the FISH staining technique), and CGH array.

An 11q deletion involving regions ouside the JS crititcal region causes a different genetic condition.

The range and severity of symptoms varies, greatly depending on the exact location and size of the missing genetic material. Symptoms commonly associated with partial monosomy 11q include abnormally slow growth before and after birth (prenatal and postnatal growth delay), moderate to severe delay in skills requiring coordination of mental and muscular activity and intellectual disability Most affected persons have mild to severe intellectual disability but rarely, individuals may have normal-borderline intelligence. Characteristic physical abnormalities may include short stature, unusual shape of the head and face (craniofacial dysmorphism), hands, feet, and congenital abnormality of the heart, ears, kidneys and genitalia. Bleeding due to platelet abnormalities and immunological defects are very common. The exact cause at the origin of partial loss of 11q is not fully understood.

  • Next section >
  • < Previous section
  • Next section >

Synonyms

  • 11q- syndrome, partial
  • 11q terminal deletion disorder
  • deletion 11q syndrome, partial
  • distal 11q monosomy
  • distal 11q- syndrome
  • Jacobsen syndrome
  • JS
  • monosomy 11q, partial
  • partial monosomy of long arm of chromosome 11
  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Signs & Symptoms

Symptoms and physical characteristics associated with partial monosomy 11q vary greatly depending on the exact size and gene content of the deleted material on chromosome 11. For a complete genetic assessment it is important that both traditional chromosome tests and CGH array are performed. No specific feature has been seen in every person, so it is important to note that affected children will not have all of the symptoms discussed below.

Physical development: Many individuals with partial monosomy 11q would reach an adult height that is well below average (short stature). Some children with partial monosomy 11q may have low levels of a growth hormone known as insulin growth factor-1 (IGF-1) and may have very short stature.

Intellectual development: Affected infants and children may experience delays in reaching developmental milestones (psychomotor developmental delay) and behavioral problems. Rarely, intelligence may be borderline-normal, but in most children have mild to moderate intellectual disability. Affected infants may also have severe speech impairment. The degree of speech impairment and intellectual disability are usually associated with larger deletions. Individuals with smaller deleted segments are more likely to have borderline intelligence and less severe symptoms overall. About a half of affected individuals haves autism or autistic behaviour.

A specific finding frequently associated with partial monosomy 11q (85% of cases) is thrombocytopenia, a condition characterized by a reduced number of platelets. Normal platelets are tiny, specialized blood cells that, in case of vascular damage, help prevent bleeding by forming clots. When a blood vessel is injured, platelets travel to the site of injury and clump together to form a clot that stops bleeding. Infants with partial monosomy 11q very frequently have a low number of platelets which causes them to bruise easily and bleed excessively. They may be at risk of internal bleeding. As affected individuals age, platelet numbers usually increase, but many individuals still bruise easily and experience prolonged bleeding episodes suggesting that the platelets are not functioning properly.

The bleeding abnormalities associated with partial monosomy 11q are extremely similar to a bleeding disorder called Paris-Trousseau syndrome (PTS). Some researchers believe these disorders are actually one disorder; some believe PTS is a variant of partial monosomy 11q; and others believe that they are similar, yet distinct, disorders. Virtually all children with Jacobsen syndrome have thrombocytopenia/thrombocytopathia, and it is extremely important to assume that platelet functions may be impaired even when their number is normal. Blood or platelet transfusion must be considered before and during surgery.

Another common disorder in patients with 11q deletion is immunodeficiency with a deficit of cellular and/or humoral immunity. As a consequence, children with JS have frequent infections of ears, respiratory tract, skin, etc and may not produce enough antibodies after vaccinations.

Many infants with partial monosomy 11q exhibit distinctive facial features including skull deformities (macrocrania or abnormal skull shape caused by craniosynostosis), high prominent forehead, facial asymmetry, widely spaced eyes (hypertelorism), crossed eyes (strabismus), drooping eyelids (palpebral ptosis) and the presence of tiny folds of skin on either side of the nose that may partially cover the eyes’ inner corners near the nose (epicanthal folds). The nasal bridge is broad and the nose is short; nostrils that are flared forward (anteverted nares); thin upper lips; down-turned mouth; small lower jaw (micrognathia); low-set and small malformed (dysplastic) ears. Children have small baby teeth but permanent teeth are usually large and some individuals may develop dental abnormalities.

Infants with partial monosomy 11q may also have abnormalities of the hands and feet: minor webbing of the fingers (skin syndactyly); thin fingers; abnormal curving of the pinky so that is bent toward the ring finger (clinodactyly); the presence of a single crease across the palms of the hands (simian crease); big and long allux with short toes; an abnormally twisted position of feet (talipes equinovarus or clubfoot). In addition, in many children, certain joints may become fixed or stuck in a bent position (contractures). A contracture occurs when thickening and shortening of tissue such as muscle fibers causes deformity and restricts movements of affected areas, especially the joints. Scoliosis (abnormal curve of the spine) may develop during adolescence.

More than half of individuals with partial monosomy 11q show heart abnormalities that are present at birth (congenital heart defects). The most common congenital heart defects associated with partial monosomy 11q are ventricular septal defects (VSDs) and left-sided obstructive lesions. The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, is the main vessel of arterial circulation, and carries blood from the left ventricle and away from the heart.

Ventricular septal defects (VSDs) can occur in any portion of the ventricular septum. The size and location of the defect determine the severity of the symptoms. Small ventricular septal defects may close without treatment (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive cardiac failure). Symptoms associated with cardiac failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, unusually fast heartbeat (tachycardia) and/or failure to grow at the expected rate (failure to thrive). Large ventricular septal defects can cause life-threatening complications during infancy. Persistent elevation of the pressure within the artery that carries blood away from the heart and to the lungs (pulmonary artery) can cause permanent damage to the lungs.

Left-sided obstructive lesions are defects that prevent the adequate blood flow from the heart. Such defects that have been associated with partial monosomy 11q include narrowing of aorta (aortic coarctation); narrowing of the valve that connects the left ventricle to the aorta (aortic valve stenosis); narrowing of the valve of that connects the lower and upper left chamber of the heart (mitral valve stenosis) and hypoplastic left heart syndrome, a group of closely-related defects characterized by underdevelopment (hypoplasia) of the left side of the heart and associated structures.

Additional heart defects that have been reported in some individuals with partial monosomy 11q include double outlet right ventricle, in which both the pulmonary artery and aorta connect to the right ventricle (the aorta normally connects to the left ventricle); transposition of the great arteries, in which the two large (great) arteries arise from the wrong area of the heart. The aorta arises from the right ventricle and the pulmonary arises from the left ventricle; aberrant right subclavian artery, in which one of the main arteries supplying blood to the upper arms and legs arises from the wrong area of the heart; and atrioventricular septal canal defects, in which the partitions (septa) and valves separating the right and left chambers of the heart are improperly developed.

Cardiac abnormalities are usually present at birth, they can be very severe and require very early surgery in the neonatal period. However vascular stenosis (including aortic stenosis) may develop in some patients later in life.

Individuals with partial monosomy 11q frequently have middle ear infections (otitis media) and inflammation of the sinuses (sinusitis). Some individuals with partial monosomy 11q experience some degree of hearing impairment.

Additional findings have been associated with partial monosomy 11q. These finding affect less than half of affected individuals. In some cases, the fibrous joints (metopic sutures) between the two sides of the bone in the forehead (frontal bone) may close prematurely (craniosynostosis). As a result, the head may have an unusual appearance with an abnormally prominent forehead “triangular-shaped head when looked from above” (trigonocephaly). If craniosynostosis compromises the growth of the skull, there is indication for a early skull surgery (craniotomy), that would allow the head to develop.

Additional findings affecting the eyes may occur including absence of some tissue from the colored portion of the eye (iris coloboma), giving the eye a “keyhole” appearance and improper developed of the nerve-rich membrane lining the eyes (retina). The retina converts visual images into nerves, which are then relayed to the brain. In some individuals with partial monosomy 11q a condition called tortuosity of the retinal vessels may occur. In this condition, the tiny vessels that supply blood to the retina may be twisted and malformed.

Eczema, a skin condition in which individuals develop an inflamed, scaly, red rash that is often itchy, may also occur. Due to the immune defect, the skin can develop bacterial, viral (wart) and or fungal infections. After an injury, the scar may develop abnormally below the normal layer of skin tissue (atrophic scars) or, conversely, there may be enlarged, raised scars called keloids.

Some individuals may develop gastrointestinal problems at birth including feeding difficulties, abnormal narrowing (stenosis) of the band of muscle fibers (pyloric sphincter) at the junction between the stomach and small intestine (pyloric stenosis), resulting in obstruction of the normal flow of stomach contents into the small intestine. Pyloric stenosis can cause affected individuals to vomit forcefully and may result in dehydration, a problem that is observed in the neonatal period. Surgical treatment of pyloric stenosis may be necessary. Children with Jacobsen syndrome often suffer from chronic constipation that would benefit from oral administration of edible oil.

Some affected infants may also have abnormalities of the genital and urinary (genitourinary) systems. For example, females may have an abnormal passage between the bladder and the vagina (vescicovaginal fistula) (rare). In affected males, the urinary opening (meatus) may appear on the underside of the penis (hypospadias); the testes may fail to descend into the scrotum (cryptorchidism); and/or portions of the large intestine may protrude through an abnormal opening in muscles of the groin (inguinal hernia).

Some infants with partial monosomy 11q may also have kidney (renal) abnormalities such as a horseshoe kidney (abnormally shaped kidneys) and duplicate kidney and/or a duplicate ureter, the small, thin tube that connects the kidneys to the bladder. The ureters drain urine through the muscular contractions. Most individuals in general population have two ureters (one connected to each kidney). A duplicate ureter is an extra ureter that may or may not be associated with any symptoms depending upon their exact location, whether they are malformed and whether they hinder the flow of urine. Kidney malformations are not always associated with obvious symptoms, but clinical problems may arise later in life, therefore an ultrasound scan of the abdomen is required to detect any kidney malformation and allow early monitoring of clinical conditions.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Causes

Partial monosomy 11q is a rare disorder in which a portion of the long arm (q) of chromosome 11 is missing (deleted). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Each human cell has 46 chromosomes: 23 are derived from the father and 23 from the mother. Pairs of human chromosomes are numbered from 1 through 22, and the additional 23rd pair is that of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. When stained, chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The range and severity of symptoms associated with this disorder depend in part upon the exact length and location of the deleted portion of chromosome 11q. In general, if less of the chromosome is missing, there may be fewer symptoms; if more of the chromosome is deleted, there may be more symptoms. In individuals with partial monosomy 11q and Jacobsen syndrome, the deleted portion of 11q tends to begin within or slightly below band 11q23 (breakpoint) and extend toward the end or “terminal” portion of chromosome 11q (qter). The symptoms of partial monosomy 11q result from the deleted genes, that are normally present on the missing portion of chromosome 11. Researchers have suggested that the region consistently missing in individuals with the disorder is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (JS critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests and CGH array.

An 11q deletion involving regions ouside the JS crititcal region causes a different genetic condition.

The exact cause of the chromosomal alteration in partial monosomy 11q is not fully understood. The medical literature has indicated that most documented cases appear to be due to a spontaneous genetic change (mutation) that occurs for unknown reasons. It is usually sporadic: only one case in a family and both parents have normal chromosomes (de novo). Less frequently a deletion 11q is the result of gametic (ovum or sperm) formation in an individual who is carrier of a chromosomal balanced translocation. A translocation is balanced if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes (no part of chromosome is missing or additional). If a chromosomal rearrangement is balanced, it is usually harmless to the carrier. However, the carrier has a very high risk of forming abnormal gametes and therefore, abnormal chromosomal disorders in the offspring. In these families a number early miscarriages may occur. Furthermore in these cases, the clinical features of children may be influenced also by additional imbalances of other chromosomes than 11. Chromosomal testing and the use of the FISH banding technique can determine whether a parent has a balanced translocation, while, as already mentioned, array CGH would show normal results as the parental abnormality is balanced. In the families where a parent has a balanced translocation, the risk for unbalanced offspring is high and prenatal diagnosis is offered.

More recently, however, researchers have speculated that inheritance of a rare, fragile site or sites on the long arm of chromosome 11 may play a role in causing the disorder in some cases. Such a fragile site (or “folate-sensitive fragile site”), designated “FRA11B”, has been linked to band 11q23.3. Inheritance of FRA11B and subsequent breakage at this site during early embryonic development may give rise to the disorder in some individuals. Reports have indicated that the mothers of some affected individuals have been carriers for FRA11B and that FRA11B has been the deletion breakpoint. In addition, based upon evidence that the 11q breakpoint is sometimes beyond (i.e., telomeric to) FRA11B, some researchers suggest that there may be other fragile sites within or below11q23.3 in addition to FRA11B. In reported cases with breakpoints telomeric to FRA11B, the deleted chromosome has been paternal in origin, indicating that the tendency for a certain breakpoint may differ based upon the parental origin of the deleted chromosome. In the families where a parent has a fragile site, prenatal diagnosis is suggested, however the recurrence of the deletion in the offspring is uncommon.

Patients with Jacobsen syndrome who have children can transmit the deleted chromosome with a 50% risk. In the families where a parent has JS, prenatal diagnosis is offered.

In most cases, of Jacobsen syndrome individuals have an altered chromosome 11q in every cell of the body. However, some individuals have a mix of cells, some cells with an altered chromosome 11q and some with normal chromosomes 11.This condition is termed mosaicism and is generally associated with less severe symptoms or even, with no symptoms at all. In fact if a person has very few cells with the 11q deletion, that person may appear clinically normal.

Individuals with the mosaic form of 11q deletion can transmit the deleted chromosome to their offspring, but the risk is unpredictable. In the families where a parent has 11q deletion mosaicism, prenatal diagnosis is offered.

Some researchers believe the FLI1 gene on the long arm of chromosome 11 plays a role in the development the bleeding complications (Paris-Trousseau syndrome) associated with partial monosomy 11q. The extra function and role of this gene is unknown. More research is necessary to identify the specific genes (and their functions) associated with the symptoms of partial monosomy 11q.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Affected populations

Partial monosomy 11q is an extremely rare chromosomal disorder that is apparent at birth. The disorder was initially described in the medical literature in 1973. Since that time, more than 200 cases have been described in the medical literature. According to some sources, more females are affected than males. The prevalence has been estimated at 1/100,000 births.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Diagnosis

Partial monosomy 11q may be diagnosed based upon a thorough clinical evaluation, the identification of characteristic physical findings, including low platelets and chromosomal studies and/or array comparative genomic hybridization (CGH) studies that demonstrate missing (deleted) material on chromosome 11q. Chromosome studies can be done on a blood sample. Chromosomes are analyzed after a laboratory procedure that includes a culture of cells obtained from a small amount of blood, and staining procedures. These chromosomes are stained so that they can be viewed more easily and are then examined under a microscope where the missing segment of chromosome 11q can be detected (high resolution karyotype). To determine the precise breakpoint on 11q, more a sensitive test may be necessary such as: fluorescent in situ hybridization (FISH), a diagnostic test in which probes marked by a specific color of fluorescent dye attach to a specific chromosome allowing researchers to better view that specific region of a chromosome.

Array CGH is a method in which a normal DNA is mixed with patient’s DNA to detect gains (duplications) or losses (deletions) of chromosomal regions. Array CGH allows a very precise definition of breakpoints in the 11q deletion, and would allow detection of even very small imbalances, which, due to their size, cannot be detected by traditional chromosome studies. Array CGH would also detect any additional imbalances, if present, but it cannot detect any balanced rearrangement (such as a parental balanced translocation). A balanced translocation can only be diagnosed by a chromosome analysis and the FISH staining technique, if present in one parent or sibling of the affected child.).

In some children, the diagnosis of partial monosomy 11q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may show a partial monosomy of chromosome 11q, especially when the test is performed because of a specific indication (one parent is affected with Jacobsen syndrome /one parent has the mosaic form of JS/one parent has a balanced translocation involving 11q/ one parent has a fragile site). In some cases this chromosome abnormality has been missed using standard chromosome tests only, but not when array CGH is performed.

Prenatal cell-free DNA screening (NIPT= non invasive prenatal test) is a test that is performed from a sample of maternal blood. The test examines fetal DNA in the maternal bloodstream. However it is not a diagnostic test.

A diagnostic test is a highly sensitive and specific test indicated to detect a condition on a population at risk, a screening test is indicated for general population without a specific risk, it must be clear that false positive and false negative results may be reported in a screening test. Therefore in case of a positive screening test a diagnostic test is usually required.

The diagnosis of clinical abnormalities that may occur in association with partial monosomy 11q must be confirmed by clinical observation and specialized imaging studies and/or additional tests. For example, congenital heart defects may be confirmed by a thorough clinical examination and specialized tests that allow physicians to evaluate the structure and function of the heart. These tests may include X-ray studies, electrocardiogram (EKG), echocardiogram, and cardiac catheterization. X-ray studies may reveal abnormal enlargement of the heart (cardiomegaly) or malformation of other heart structures. An EKG, which records the heart’s electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, ultrasonic waves are directed toward the heart, enabling physicians to study cardiac function and motion. During cardiac catheterization, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart, measure the pressure within the heart, and/or thoroughly identify anatomical abnormalities.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Standard Therapies

Treatment
The treatment of partial monosomy 11q is directed toward the specific symptoms that are apparent in each individual. Treatment usually requires the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, hematologists, immunologists, ear, nose and throat specialists, dental specialists, speech pathologists, specialists who assess and treat eye problems (ophthalmologists), specialists who assess and treat disorders affecting the hormones and glands (endocrinologists), specialists who assess and treat disorders of the skeleton (orthopedists) and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.

Physicians must regularly monitor affected individuals who tend to exhibit low platelet counts (thrombocytopenia) to ensure proper preventive measures and early, prompt treatment.Some affected individuals may be treated with platelet transfusion or desmopressin acetate, a drug that helps the blood clot. Blood or Platelet transfusion may be necessary before or during surgeries.

In practice: It must be assumed that ALL patients with JS have a specific bleeding disorder called Paris-Trousseau syndrome. Paris-Trousseau has two components:

1) Severe thrombocytopenia (low platelet count) of the newborn, which usually returns to near- or low-normal platelet counts during childhood
2) Persistent platelet dysfunction

It should be assumed that all patients with JS are at risk for potentially life-threatening bleeding, especially in case of traumas or major surgeries.

Medications that impair normal platelet function (e.g., ibuprofen, aspirin) should always be avoided. Desmopressin (DDAVP) IV or nasal spray may improve platelet aggregation during dental procedures, in case of mouth or nose bleeding.

Oral contraceptives are indicated for females with heavy periods.

Platelet or full blood transfusion may be needed for serious bleeding or before and during major surgeries

Patients with JS should have a complete blood count monthly for the first 3 months, then once per year. Platelet function studies should be done once the platelet count normalizes.

Assume that JS patients are at risk for severe bleeding even in case of apparently normal platelet count and function.

In many children, treatment would include surgical repair of certain malformations. For example, surgery may be performed to correct certain cardiac, craniofacial, ocular, skeletal, genitourinary, renal and/or other malformations that may be associated with this disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.

For example, in affected children with craniosynostosis and trigonocephaly, surgery may be performed to help correct the premature closure of bones in the skull. In addition, certain congenital heart abnormalities occurring in association with partial monosomy 11q (e.g., ventricular septal defects) may be corrected surgically. Complications of certain congenital heart defects (e.g., rapid heartbeat [tachycardia], fluid accumulation, etc.) may be treated with a variety of drugs such as those that may help prevent or correct abnormal heart rhythms (antiarrhythmics) and/or medications that help to eliminate excessive fluid from the body (diuretics).

In addition, nutritional considerations may be important in infants with VSDs, ASDs, and/or certain other congenital heart defects. Respiratory infections should be treated vigorously and early. Because of the risk of bacterial infection of the lining of the heart (endocarditis) and the heart valves, individuals with VSDs, ASDs, and/or certain other heart defects may be given antibiotic drugs before any surgical procedure, including dental procedures such as tooth extractions.

In affected children with eye abnormalities (e.g., iris colobomas, strabismus, ptosis etc.), surgery and/or other measures may be used to help treat and/or correct such malformations. Corrective glasses, contact lenses, surgery, and/or other measures may also be used to help improve visual problems associated with such ocular abnormalities.

In some children, abnormalities involving the joints, tendons, muscles, and bones (orthopedic), such as flexion contractures, scoliosis, clubfeet, and/or other abnormalities of the hands and/or feet may be treated by orthopedic techniques, potentially in combination with surgery. Again, the procedures used will depend upon the severity and location of the abnormalities and their associated symptoms. Physical therapy may also be prescribed to help improve coordination of certain movements (mobility).

Early intervention is important in ensuring that children with partial monosomy 11q reach their highest potential. Services that may be beneficial may include special remedial education and other medical, social and/or vocational services.

Genetic counseling is recommended for affected individuals and their families.

Immunological issue

People with Jacobsen syndrome are at significantly increased risk for having an impaired immune system, i.e. immunodeficiency, which can lead to life-threatening infection, and/or more frequent less serious infections. The type and severity of immunodeficiency is highly variable.

Types of immunodeficiency that have been identified in people with JS:

1. common variable immune deficiency
2. hypogammaglobinemia
3. T-cell lymphopenia (including severe T-cell lymphopenia)
4. combined (B and T cell) immunodeficiency

Testing is recommended for all people with Jacobsen syndrome.

• Newborns should have T cells measured soon after birth
• At age 4-6 months, measure Immunoglobulins (IgG, IgA, IgM)
• At age 12 months, measure antibody titers for routine vaccinations such as tetanus and diphtheria
• At 2 years, consider administration of Pneumovax (23 valent pneumococcal polysaccharide vaccine) and measurement of post vaccination titers. This helps to identify patients who may lack the ability to mount appropriate immune responses. Using this vaccine has the additional benefit of enhancing protection to Streptococcus pneumoniae in immunocompetent patients.

Older children and adults with JS and a pattern of recurrent infections should be evaluated for the presence of immunodeficiency with similar testing as described above. Consultation with an allergist/immunologist familiar with the evaluation and treatment of patients with immunodeficiency may facilitate diagnosis. Abnormal screening tests, concern for immune deficiency or recognition of a pattern of recurrent infections should prompt earlier evaluation, treatment and referral to an immunologist.

Recommendations based on what is known to date regarding immunodeficiency in JS:

• Routine vaccinations and COVID vaccine should be given unless there is a known T cell deficiency
• Pneumovax-23 at approximately 2 years of age or in older patients with recurrent infections being evaluated for immunodeficiency
• Early treatment of infections with antibiotics
• Repeat immunologic evaluation if infections are recurrent or severe (even if tests were normal the first time)
• Synagis (to prevent RSV infection) should be strongly considered in children less than 2 years with recurrent respiratory symptoms or any immunologic abnormality, even in the absence of cardiac issues.
• Some patients with low T cell numbers may benefit from prophylactic antibiotics, especially if the T cell number is felt to increase their risk of opportunistic infections. ther patients with hypogammaglobulinemia and recurrent infections may also benefit from certain antibiotic regimens. Immunologists often prescribe prophylactic antibiotics in an attempt to reduce the frequency and severity of sinopulmonary infections caused by encapsulated organisms.
• The use of intravenous or subcutaneous immunoglobulin replacement for patients with JS should follow the current recommendations for its use in patients with immunodeficiency.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Clinical Trials and Studies

Some individuals with partial monosomy 11q have low levels of a specific growth hormone (IGF-1). It is unknown whether treatment with growth hormone replacement therapy would be of benefit for these individuals. More research is necessary to determine the effectiveness and safety of such therapy in these specific cases of partial monosomy 11q.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Contact for additional information about chromosome 11, partial monosomy 11q:

Prof. Teresa Mattina
Medical Geneticist
Scientific Foundation and Clinic G.B. MORGAGNI, Catania, Italy
Formerly DirettoreScuolaSpecializzazioneGeneticaMedica
Centro di Riferimento Regionale Universita’ di Catania, Italy
Diagnosi e Cura delle Malattie Genetiche
mobile 328 2215704
mattina@unict.it
mattina@hotmail.it

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

References

TEXTBOOKS
Kardon NB.Chromosome 11, Partial Monosomy 11q.NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:60-61.

Gorlin RJ, Cohen MM Jr, Hennekam RCM, eds. Syndromes of the Head and Neck. 4th ed. New York, NY: Oxford University Press; 2001:99.

JOURNAL ARTICLES
Melis D, Genesio R, Cozzolino M, et al. An emerging phenotype of proximal 11q deletions. Eur J Med Genet. 2010;53(5):340-3.

Mattina T, Perrotta CS and Grossfeld P. Jacobsen syndrome. Orphanet J Rare Dis. 2009; 4:9. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-9
Tyson C, Qiao Y, Harvard C, et al. Submicroscopic deletions of 11q24, 25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH. MolCytogenet. 2008;1(1):23.

Valduga M, Cannard VL, Philippe C, et al. Prenatal diagnosis of mosaicism for 11q terminal deletion. Eur J Med Genet. 2007;50:475-481.

White JG. Platelet storage deficiency in Jacobsen syndrome.Platelets. 2007;18:522-527.

Grossfeld PD, Mattina T, Lai Z, et al. The 11q Terminal Deletion Disorder: a prospective study of 110 cases. Am J Med Genets A. 2004;129:51-61.

Haghi M, Dewan A, Jones KL, et al. Endocrine abnormalities in patients with Jacobsen (11q-) syndrome. Am J Med Genet A. 2004;129:62-63.

Lee WB, O’Halloran HS, Grossfeld PD, et al. Ocular findings in Jacobsen syndrome.J AAPOS. 2004;8:141-145.

Raslova H, Komura E, Le Couedoc JP, et al. FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia. J Clin Invest. 2004;114:77-84.

Favier R, Jondeau K, Boutard P, et al. Paris-Trousseau syndrome: clinical, hematological, molecular data of ten new cases. ThrombHaemost. 2003;90:893-897.

Jones C, Müllenbach R, Grossfeld P, et al. Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage. Hum Mol Genet. 2000;9(8):1201-1208.

Sirvent N,
F, Pedeutour F, et al. Jacobsen’s syndrome, thrombopenia and humoral immunodeficiency. Arch Pediatr. 1998; 5(12):1338-1340.

INTERNET
Online Mendelian Inheritance in Man (OMIM).The Johns Hopkins University.Jacobsen Syndrome; JBS. Entry No: 147791. Last Edited 04/03/2020. Available at: https://omim.org/entry/147791 Accessed May 25, 2023.

Grossfeld P. Jacobsen syndrome.Orphanet. Last Update March 2020 https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=518&Disease_Disease_Search_diseaseGroup=Jacobsen-syndrome&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Jacobsen-syndrome&title=Jacobsen-syndrome&search=Disease_Search_Simple Accessed May 25, 2023.

  • < Previous section
  • Next section >

Programs & Resources

RareCare® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations


National Organization for Rare Disorders