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Marker chromosome 15 syndrome

This is part of Rare diseases.

Diagnosis: Marker chromosome 15 syndrome

Synonyms: Idic (15) syndrome, Isodicentric 15 syndrome

Innehåll


Date of publication: 2012-08-20
Version: 1.0

ICD 10 code

Q99.8

The disease

Marker chromosome 15 syndrome is caused by a congenital extra chromosome, a marker chromosome, and leads to intellectual disability, autism-spectrum disorder and, often, epilepsy. Marker chromosome 15 syndrome was described for the first time in England in 1974 by J Watson and RR Gordon.

Occurence

Approximately three in every 100,000 children are born with the syndrome, indicating that approximately three children are born with the condition every year in Sweden. There are considerably more children with another type of marker chromosome 15, which does not give rise to any symptoms.

Cause

Marker chromosome 15 syndrome is caused by a chromosome abnormality. As well as the normal 46 chromosomes there is a small, extra chromosome, a marker chromosome, which differs from the others and brings the total to 47 chromosomes. In this particular case the marker chromosome consists of genetic material from chromosome 15, in the form of an isodicentric chromosome, idic(15). It contains two copies of the short arm of chromosome 15, as well as a little piece of the upper part of the long arm. Instead of the normal two copies of genes, people with marker chromosomes have three or four copies of this particular chromosome region.

Figure: On the left is a normal copy of chromosome 15. On the right, the marker chromosome consists of a double, mirror-image copy of the upper part of the chromosome.

A smaller and more common variant of marker chromosome 15, which does not cause symptoms, has also been described. The asymptomatic variant consists of an extremely small amount of extra genetic material, while the symptomatic variant includes a larger amount of the long arm of chromosome 15. It is vital to discover whether the marker chromosome includes the Prader-Willi/Angelman region (PWAR) of the chromosome, a region which is deleted in Prader-Willi and Angelman syndromes. If PWAR is included in the marker chromosome, the individual will have marker chromosome 15 syndrome.

Heredity

Marker chromosome 15 syndrome usually occurs as a new mutation, where the genetic mutation arises for the first time in an individual, and is not inherited. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with the extra chromosome risks passing it on to his/her children, although it is rare for people with marker chromosome 15 syndrome to have children.

The more common, smaller variant of marker chromosome 15 is often inherited and does not cause symptoms.

Symptoms

The most common symptoms associated with marker chromosome 15 syndrome include: intellectual disability, delayed motor development and low muscle tone (hypotonia), language, speech and communication difficulties, autism spectrum disorders and epilepsy.

Everyone with marker chromosome 15 syndrome has an intellectual disability, usually moderate to severe. Individuals with intellectual disability require more time to understand things and to learn new skills. They have problems learning, processing information, orienting themselves in new situations, taking a holistic view and understanding connections and associations. Therefore, it may take them longer to express their thoughts, wishes and feelings. This intellectual disability is associated with delayed language development and with delayed development of fine and gross motor skills.

Most people with marker chromosome 15 syndrome have autism or autism-like symptoms, including limited ability to engage in social interaction through verbal and non-verbal communication. This affects the way they perceive events and their ability to act and affect different situations.

Other common symptoms include anxiety and hyperactivity or other symptoms of ADHD (Attention-Deficit/Hyperactivity Disorder) as well as stereotypical movements.

Most children with marker chromosome 15 syndrome sit and walk later than their peers because of their general intellectual disability and delayed motor development. Some children have problems coordinating their movements. A contributing factor is low muscle tone (hypotonia), which also affects fine motor skills and makes the child appear clumsy. Hypotonia can also cause digestive problems, particularly when the child is very young.

Approximately two-thirds of everyone with marker chromosome 15 syndrome develops some form of epilepsy.

Different forms of curvature of the spine (scoliosis or kyphosis) may present.

Common physical features are characteristic of people with chromosomal abnormalities. In marker chromosome 15 syndrome these characteristics are not striking, but they do include certain typical features including a broad bridge of the nose, downward-slanting eyes and squinting. Bite abnormalities are also common.

Diagnosis

The diagnosis is confirmed by a chromosome analysis establishing the presence of an extra chromosome (a marker chromosome). An exact identification of the marker chromosome can be madeusing a FISH analysis (fluorescent in situ hybridization) or array-CGH (array-comparative genomic hybridization) that can separate the variant of marker chromosome 15 which produces symptoms, from the asymptomatic variant.

Treatment/interventions

Various treatments are available to control symptoms and much can be done to provide support and help compensate for disabilities.

Early habilitation is essential to stimulate the child’s development. Early contact should be established between the child and family and a habilitation team, which includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment are offered 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. Parents and siblings may also receive support. The family may also need help coordinating interventions.

Assessments of the child’s speech, language and communication abilities are carried out by a speech therapist. Early language stimulation which includes augmentative and alternative communication (AAC) is important for the child’s development.

It is important that children with the syndrome receive an early neuropsychiatric assessment to evaluate autistic symptoms, hyperactivity and other abnormal behaviour patterns. An early assessment makes it possible to start intensive treatment to stimulate the child’s development and prevent behavioural problems.

It is important that the child’s pre-school, school and after-school centre take the developmental level and individual needs of the child into account. All information given to the child, as well as teaching and training programmes, must be customised and structured to meet the child’s needs. Children and young people with the syndrome who have autistic characteristics require a clearly structured environment, where training and other functions take place according to a carefully designed, regular, programme.

Hyperactivity, lack of impulse control and temper tantrums are often difficult for people in the immediate vicinity to deal with. Medication may be required to supplement pedagogical and psychological support measures.

Epilepsy is treated with medication.

The child should be examined at at early age by an ophthalmologist, in order to treat visual impairments such as squinting.

A physiotherapist can provide advice on how motor skills can be stimulated to best effect. Regular controls can reveal deformities of the back that may be corrected. To minimise the development of curvature of the spine (kyphosis and scoliosis) a surgical corset is often prescribed. If kyphosis and scoliosis are severe an operation may be required.

Many children with the syndrome have difficulties taking an active role in their dental care and dental hygiene. Early, regular check-ups by a specialist dentist are important for preventative dental treatment and to asses the need for dental braces.

Adults with the syndrome require continuous, individually-designed habilitation.

Practical advice

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National and regional resources in Sweden

Departments of Clinical Genetics at university hospitals are responsible for genetic diagnosis and information.

The Swedish Centre for Children and Young People with Syndromes and Congenital Conditions, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 59 42, +46 18 611 30 90.

At the Unit for Paediatric Neuropsychiatry (BNK) at The Queen Silvia Children’s Hospital, Gothenburg there is a neuropsychiatric and neuropaediatric team for children and young people with unusual diagnoses.

Resource personnel

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

Senior Physician, Suzanne Steffenburg, Unit for Paediatric Neuropsychiatry, The Queen Silvia Children’s Hospital, Otterhällegatan 12A, SE-411 18 Gothenburg, Sweden. Tel: +46 31 342 59 50, fax: +46 31 84 89 32.

Courses, exchanges of experience, recreation

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Organizations for the disabled/patient associations

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities, Gävlegatan 18 C, Stockholm. Mailing address: 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 Autism and Asperger Association, Bellmansgatan 30, SE-118 47 Stockholm, Sweden. Tel: +46 8 702 05 80, fax: +46 8 644 02 88, email: info@autism.se, www.autism.se.

SEF, The Swedish Epilepsy Association, Sturegatan 4 A, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 669 41 06, fax: +46 8 669 15 88, email: info@epilepsi.se, www.epilepsi.se.

There is an international patient association, DUP 15q Alliance.

Courses, exchanges of experience for personnel

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Research and development (R&D)

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Information material

An information leaflet on marker chromosome syndrome 15 summarising the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2011-10-24). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

A British patient association for rare chromosomal abnormalities. Unique, has a brochure which may be downloaded from its home page. In English only. www.rarechromo.org.
Search: registered disorders/disorders leaflets/Idic(15)

Books

Beckman V, Kärnevik Måbrink M, Schaumann H. Gång på gång - pedagogik vid autism och autismliknande tillstånd. (In Swedish only.) Natur och kultur, Stockholm, Sweden 1994.

Gillberg C. Autism och autismliknande tillstånd hos barn, ungdomar och vuxna. (In Swedish only.) Natur och kultur, Stockholm, Sweden 1994.

Literature

Battaglia A, Parrini B, Tancredi R. The behavioral phenotype of the idic(15) syndrome. Am J Med Genet C Semin Med Genet 2010; 15: 448-455.

Battaglia A. The inv dup (15) or idic (15) syndrome (Tetrasomy 15q). Orphanet J Rare Dis 2008; 3: 30.

Battaglia A. The inv dup (15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. Brain Dev 2005; 27: 365-369.

Blennow E, Brøndum Nielsen K, Telenius T, Carter NP, Kristoffersson U, Holmberg E et al. Characterization of 50 probands with extra structurally abnormal chromosomes by fluorescence in situ hybridization. Am J Med Genet 1995; 55: 85-94.

Gillberg C, Steffenburg S, Wahlström J, Gillberg IC, Sjöstedt A, Martinsson T et al. Autism associated with marker chromosome. J Am Acad Child Adolesc Psychiatry 1991; 30: 3: 489-494.

Leana-Cox J, Jenkins L, Palmer CG, Plattner R, Sheppard L, Flejter WL et al. Molecular cytogenetic analysis of inv dup (15) chromosomes, using probes specific for the Prader-Willi/Angelman syndrome region: clinical implications. Am J Hum Genet 1994; 54: 748-756.

Robinson WP, Binkert F, Giné R, Vazquez C, Müller W, Rosenkranz W et al. Clinical and molecular analysis of five inv dup (15) patients. Eur J Hum Genet 1993; 1: 37-50.

Schinzel A. Catalogue of unbalanced chromosome aberrations in man. 2nd revised and expanded edition. De Guyter, Berlin, New York, 2001; pp 649-647.

Watson EJ, Gordon RC. A case of partial trisomy 15. J Med Genet 1974; 11: 400-402.

Webb T. Inv dup (15) supernumerary marker chromosomes. J Med Genet 1994; 31: 585-594.

Wisniewski L, Hassold T, Heffelfinger J, Higgins JV. Cytogenetic and clinical studies in five cases of inv dup (15). Hum Genet 1979; 50: 259-270.

Database references

Orphanet, European database. www.orpha.net  
Search: idic (15)

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, Solna, 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.

Date of publication: 2012-08-20
Version: 1.0
Publication date of the Swedish version: 2011-12-29

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

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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.