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11q deletion syndrome

This is part of Rare diseases.

Diagnosis: 11q deletion syndrome

Synonyms: Jacobsen syndrome


Publication date: 2012-11-28
Version: 1.0

The disease

11q deletion syndrome is a congenital chromosomal abnormality that is almost always associated with intellectual disability. The syndrome is also known as Jacobsen syndrome after the Danish geneticist Petrea Jacobsen, who published the first case report in 1973.

Occurrence

The estimated incidence is 1 newborn per 100,000, meaning that in Sweden approximately one child is born with the syndrome every year. The syndrome is somewhat more common in girls than in boys.

Cause

11q deletion syndrome is caused by a loss of chromosomal material (a deletion) on the long arm of chromosome 11. The size and precise location of the deletion may vary, which affects clinical presentation.

In rare cases the syndrome is caused by a ring chromosome 11 formation. Chromosome 11 has then lost the ends of both the short arm (p) and the long arm (q), and the two broken ends have reunited to form a ring. The symptoms of ring chromosome 11 syndrome will be a combination of the symptoms associated with 11p deletion syndrome and 11q deletion syndrome.

The syndrome may also be caused by a structural rearrangement of chromosome material, a balanced translocation, in one parent. In a translocation there is an exchange of chromosomal material between two chromosomes, in this case between one copy of chromosome 11 and another chromosome. Apart from loss of a segment from 11q the child with the syndrome will then also have superfluous chromosomal material from another chromosome.

Heredity

If the chromosome abnormality has occurred during the formation of gametes (egg and sperm cells), both parents have normal chromosomes. The risk that they will have another child with the syndrome is then minimal.

Rare cases have been described in which the chromosome abnormality has been present in mosaic form (in some cells) in one parent. This increases the risk of having another child with the syndrome.

When the child’s chromosomal abnormality is caused by a balanced translocation in one of the parents there is a risk of recurrence in each new pregnancy. A carrier of a balanced translocation is usually asymptomatic, but fertility may be impaired and there is a risk of unbalanced chromosome rearrangements occurring during the formation of gametes. In the formation of gametes the number of chromosomes decreases by half, from 46 to 23, so that each egg or sperm cell has one chromosome from every pair. For a translocation to be balanced both the chromosomes that have exchanged genetic material need to end up in the same gamete, or the result will be an unbalanced translocation, in which the egg or sperm cell either has three copies of the translocated chromosome segments or only one copy. If the gamete with the unbalanced translocation is fertilized, the result will either be a miscarriage or the child will be born with a chromosome abnormality, almost always causing congenital malformations, abnormalities in facial features and developmental delay.

Symptoms

Most individuals with 11q deletion syndrome have intellectual disability, usually ranging from mild to moderate. The degree of intellectual disability is correlated with the size of the deletion. Individuals with intellectual disability require more time to understand and learn new skills. They may also have difficulties organising new information and adapting to new situations, and have trouble seeing how things or events relate to each other. Expressing their will, thoughts or emotions may take longer than for other children. Intellectual disability causes delayed language development, but most children with the syndrome learn to speak. In intermediate or severe forms of intellectual disability, language use is significantly restricted.

Some children with 11q deletion syndrome have behavioural problems, concentration problems and hyperactivity. Some are diagnosed with autism.

Hearing loss is common, owing to recurrent ear infections. Other symptoms vary among individuals.

Children with the syndrome may have a characteristic facial appearance, which is common in chromosome abnormalities. 11q deletion syndrome is associated with widely set eyes (hypertelorism), down-slanting palpebral fissures (the opening between the upper and lower eyelids), and drooping eyelids (ptosis). Strabismus (squinting) may also occur. Other features include a high, sometimes protruding, pointed forehead, low-set ears, a short nose with a broad bridge, a mouth with down-turned corners, a thin upper lip, and a high palate.

Finger and toe fusions (syndactyly) may occur.

More than half of all children with the syndrome have some type of heart defect, for example a hole between the two chambers of the heart (VSD, ventricle septal defect), or an underdeveloped left chamber, with or without obstruction of the aorta.

Children with the syndrome often fail to thrive and will have short stature. Feeding problems and reflux (when stomach contents leak into the lower part of the oesophagus) are common. Constipation is also common. Some children have gastrointestinal malformations, for example a blockage in the pylorus, the opening from the stomach into the small intestine (pyloric stenosis), or urinary tract abnormalities. In boys with the syndrome the testicles sometimes have not descended into the scrotum (cryptorchidism).

Individuals with the syndrome often have thrombocyte (blood platelet) deficiency, and the thrombocytes are defective. The deficiency may heal but not the defective platelets, resulting in poor blood coagulation and an increased tendency to bleeding and bruising.

Diagnosis

The diagnosis is made by a chromosome analysis of cultured blood cells or by DNA analysis.

The parents should be offered a chromosome analysis to exclude an inherited chromosomal abnormality with a risk of recurrence in future pregnancies. If one of the parents has a structural chromosome abnormality close relatives should also be offered testing, as they may also be carriers.

When the diagnosis is established the family should be offered genetic counselling and further investigations.

Prenatal diagnosis or preimplantation genetic diagnosis (PGD) are possible if the mutation in the family has been identified.

Treatment/interventions

There is no cure for the syndrome. Various treatments are available to control symptoms and much can be done to provide support and compensate as far as possible for disabilities.

Children with the syndrome should be evaluated by a paediatric cardiologist. If a heart defect is found, the cardiologist will decide on treatment.

Children with bleeding tendencies and thrombocyte deficiency should be evaluated and treated by a haematologist (a physician specialising in disorders of the blood). Medication that interferes with platelet function should be avoided.

Parents of children who have sucking and eating problems require early contact with a dietician and a speech therapist to establish good feeding routines. A child who fails to thrive should be evaluated by an endocrinologist, who will assess whether growth hormone treatment is needed.

An ophthalmologist should examine the eyes in order to identify squinting and exclude structural abnormalities. Squints are treated by covering the normal eye with a patch in order to train the affected eye.

Early ultrasound examination of the urinary tract is carried out to detect any structural defects. Undescended testicles require surgical intervention.

Habilitation should be initiated early. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Help is available within the medical, educational, psychological, social and technical fields. Habilitation may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling. It also includes information about support offered by the local authority as well as advice on the way accommodation and other environments can be adapted to the child’s needs. The whole family should be offered support.

It is important that the choice of pre-school, school and after-school centre takes the developmental level and individual needs of the child into account. Children with intellectual disability require special education.

Play and interactive games stimulate and give the child practice in speaking, language and communication. In order to aid development as much as possible the child’s linguistic and communication abilities are assessed. Educational and linguistic support are then adjusted to the individual child’s requirements and developmental level. Many of these children will benefit from learning augmentative and alternative communication (AAC) at an early age.

On learning that their child has a chromosome abnormality, many parents find themselves in emotional crisis. In this situation, the ability to deal with information on the syndrome and available support is limited. It is therefore vital that the information is repeated and that the parents are given time to ask questions and ventilate their concerns. All parents in this situation should be offered support from a social worker or psychologist. If parents wish, they should also be offered the opportunity to contact other families in a similar situation with whom they can share their experiences.

Respite care services, such as a support family or a short-term respite care facility, may offer parents and siblings temporary relief from tasks associated with caregiving. The family may also need help coordinating different forms of help.

Adults with 11q deletion syndrome usually require continued habilitative interventions adapted to their individual needs. They also need continued social support, for example in the form of special housing, offering assistance in managing daily living skills and organizing activities.

Practical advice

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National and regional resources in Sweden

Diagnostics, family risk assessment and genetic information are services provided by units for clinical genetics at university hospitals.

Resource personnel

Professor Elisabeth Blennow, Clinical Genetics, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 753 80, fax: +46 8 32 77 34.

Courses, exchanges of experience, recreation

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Organizations for the disabled/patient associations etc.

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities, Gävlegatan 18 C, Box 6436, SE-113 82 Stockholm, Sweden. Tel: +46 8 508 866 00, fax: +46 8 508 866 66, email: fub@fub.se, www.fub.se.

NOC, The Swedish National Network for Rare Chromosome Disorders, is part of FUB. Email: info@noc.fub.se, www.noc.fub.se. Among other activities, NOC organises events where families can exchange knowledge and experiences.

The Swedish Heart-Children’s Association, Kammakaregatan 47, SE-111 24 Stockholm, Sweden. Tel: +46 8 442 46 50, email: kansliet@hjartebarn.org, www.hjartebarn.org.

Courses, exchanges of experience for personnel

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Research and development

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Information material

An information leaflet on 11q deletion syndrome summarising the information in this database text is available free of charge from the Publications Department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2012-1-31.) Address: SE-106 30 Stockholm, Sweden. Fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se, or tel: +46 75 247 38 80. Postage will be charged for bulk orders.

There is a European parental network, the European Chromosome 11q Network, which has a website providing information on the syndrome and opportunities for parents to establish contact: http://11q.chromosome11.eu.

The American website “11q Research and Resource Group” is for parents and researchers with an interest in the syndrome and provides information and relevant links.

The British patient association “Unique” is for people with rare chromosomal abnormalities. Their website provides extensive information, arranged according to which chromosome is affected: www.rarechromo.org.

Literature

Grossfeld PD, Mattina T, Lai Z, Favier R, Jones KL, Cotter F et al. The 11q terminal deletion disorder: a prospective study of 110 cases. Am J Med Genet A 2004; 129: 51-61.

Hustinx R, Verloes A, Grattagliano B, Herens C, Jamar M, Soyeur D et al. Monosomy 11q: report of two familial cases and review of the literature. Am J Med Genet 1993; 47: 312-317.

Jacobsen P, Hauge M, Henningsen K, Hobolth N, Mikkelsen M, Philip J. An (11;21) translocation in four generations with chromosome 11 abnormalities in the offspring: a clinical, cytogenetical, and gene marker study. Hum Hered 1973; 23: 568-585.

Jones C, Müllenbach R, Grossfeld P, Auer R, Favier R, Chien K 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: 1201-1208.

Mattina T, Perrotta CS, Grossfeld P. Jacobsen syndrome. Orphanet J Rare Dis 2009; 7: 4-9.

Mohamed AN, Ebrahim SA, Aatre R, Qureshi F, Jacques SM, Evans MI.
Prenatal diagnosis of a de novo ring chromosome 11. Am J Med Genet 2001; 102: 368-371.

Lee WB, O’Halloran HS, Grossfeld PD, Scher C, Jockin YM, Jones C. Ocular findings in Jacobsen syndrome. J AAPOS 2004; 8: 141-145.

Lewanda AF, Morsey S, Reid CS, Jabs EW. Two craniosynostotic patients with 11q deletions, and review of 48 cases. Am J Med Genet 1995; 59: 193-198.

Palka G, Verrotti A, Peca S, Mosca L, Lombardo G, Verotti M et al. Ring chromosome 11. A case report and review of the literature. Ann Genet 1986; 29: 55-58.

Penny LA, Dell´Aquila M, Jones MC, Bergoffen J, Cunnniff C, Fryns JP et al. Clinical and molecular characterization of patients with distal 11q deletions. Am J Hum Genet 1995; 56: 676-683.

Schinzel A. Catalogue of unbalanced chromosome aberrations in man. 2nd edition. Walter de Greyter, Berlin, New York 2001.

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

Wenger SL, Grossfeld PD, Siu BL, Coad JE, Keller FG, Hummel M. Molecular characterization of an 11q interstitial deletion in a patient with the clinical features of Jacobsen syndrome. Am J Med Genet A 2006; 140: 704-708.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: jacobsen syndrome

Genetics Home Reference
www.ghr.nlm.nih.gov
Search: jacobsen syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Elisabeth Blennow, Karolinska University Hospital, Stockholm, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 2012-11-28
Version: 1.0
Publication date of the Swedish version: 2012-05-16

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.