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Cri du chat syndrome

This is part of Rare diseases.

Diagnosis: Cri du chat syndrome

Synonyms: 5p deletion syndrome

Innehåll


Date of publication: 2006-06-26
Version: 3.1

The disease

Cri du chat syndrome is a chromosomal disorder that causes intellectual disability. A number of other symptoms are also associated with the syndrome, for example heart defects. The first case report was published in 1963 by the French paediatrician and geneticist Jerôme Lejeune.

Cri du chat is French for "cat cry", and the syndrome takes its name from the newborn infant's characteristic high-pitched cry. The disorder is also known as 5p deletion syndrome.

Occurrence

The syndrome occurs in two individuals per 100,000 births. This means that in Sweden, 1-2 children are born with the condition every year. Significantly more girls than boys are affected. Approximately one hundred Swedish cases are known.

Cause 

Cri du chat syndrome is caused by a deletion (loss of a segment of DNA) on the outermost band of the short arm (p) of chromosome 5 (5p15.32-33). The severity of the condition depends on the size and location of the deletion. In 80-85 per cent the deletion has occurred during the formation of gametes, usually in the development of sperm.

In 10-15 per cent of these children, the cause of the syndrome is a chromosome rearrangement known as a balanced translocation in one of the parents. A balanced translocation occurs when chromosomes break, producing unstable sticky ends. Generally, repair mechanisms rejoin the sticky ends of the broken chromosomes, but there is a risk that wrong ends meet so that genetic material is exchanged between two different chromosomes. Since no genetic material has been lost or added, the parent remains healthy. There is, however, a risk that a parent with a balanced chromosome translocation will have more than one child with the syndrome.

In approximately 1 per cent, the cause of the syndrome is a chromosome arrangement known as ring chromosome (meaning that parts of both arms of chromosome 5 have been lost and the two broken ends have reunited to form a ring), mosaicism (when the chromosome defect is only present in some cells), or some other extremely rare chromosome aberration.

Heredity

In most children with the syndrome (80-85 per cent), the disorder is caused by a new mutation, meaning that the deletion in chromosome 5 has not been inherited and is not present in the affected individual's family.

Approximately 10-15 per cent of the children have inherited a translocation chromosome from one parent. The translocation results when a segment from chromosome 5 switches places with a segment on another chromosome. If the exchange does not cause any loss or excess of chromosomal material, the translocation is said to be balanced. The carrier of a balanced translocation usually remains asymptomatic, but there is a risk that an unbalanced translocation will occur in the formation of gametes. The result may be fertility problems, a higher risk of miscarriage, or of having children with an unbalanced translocation. Individuals with unbalanced translocations generally have intellectual disabilities, delayed growth, and/or congenital malformations.

A child with a deletion in chromosome 5 resulting from an unbalanced translocation also has a redundant third copy of another chromosome segment. Specific symptoms will present, depending on the nature of the chromosome abnormality.

The risk that a parent with a balanced translocation will have another child with cri du chat syndrome is higher than if the disorder results from a new mutation. The estimated risk is 10-15 per cent.

Symptoms

Newborns with cri du chat syndrome virtually always have a weak, high-pitched monotone cry. The reason is a small larynx and short vocal cords. The characteristic cry usually changes within a few months, as a rule before the age of one. However, the voice remains high-pitched.

These children tend to have low birth weight, despite full-term pregnancies. They grow and gain weight slowly, and they are often small and fine-limbed.

Approximately 30 per cent have congenital heart defects, the most common one being patent ductus arteriosus (when the passageway between the left pulmonary artery and the aorta does not close properly after the child's birth). A few children have more complex heart defects.

Some children have cleft lip and palate. Skeletal abnormalities such as club foot, malformed vertebrae (hemivertebrae) and scoliosis (abnormal curvature of the spine) occur, but are relatively rare. Kidney malformations and groin hernias also occur.

Constipation is a common problem, particularly during the first year of life, although the problem may persist through childhood and adolescence.

Many of these children are susceptible to infections, and have recurrent respiratory tract and ear infections. Children with very low muscle tone are particularly sensitive, as they have trouble breathing and coughing up phlegm. Untreated ear infections may result in hearing impairment. After a few years, the children are less prone to infections.

Bite problems are common, particularly an open bite in the region of the front teeth. The combination of poor oral motor skills, low muscle tone and bite problems often lead to difficulties in sucking, masticating and swallowing. Sucking problems in newborns may be exacerbated if the general health of the child is affected, for instance by a heart defect. Drooling and snoring are also relatively common.

Many children with cri du chat syndrome have a characteristic appearance. Distinct features include a small head with a round face and small chin. A low nasal bridge is common. The eyes may have a downward slant and are often widely set (hypertelorism), and skin folds may cover the inner corners of the eyes (epicanthal folds). Strabismus presents in approximately 50 per cent of all cases. About 80 per cent of children with the syndrome have a simian crease in the palms of their hands.

Children with cri du chat syndrome have substantially delayed psychomotor development and varying degrees of low muscle tone (hypotonia). Poor fine motor skills result in coordination problems. Some children have hypermobile joints. Varying degrees of intellectual disability are associated with the syndrome, ranging from mild to severe. Language acquisition is delayed, and these children often do not speak their first words until they are between the ages of 3 and 6. Some only learn a small number of words, while others learn to speak full sentences. However, these children understand considerably more than they can express, and usually more than people around them believe.

Individuals with cri du chat syndrome often have concentration problems and hyperactivity is very common. They may be moody (laughing and crying easily) and are sensitive to the ambiance around them. They may also be vulnerable to criticism. Sleeping problems are common, especially in children, as they may find it difficult to relax. Behaviour disturbances such as self-stimulation and self-destructive activities, including head banging, stereotypical movements and hand sucking, are common and often begin early. Most children with the syndrome are also sensitive to loud noises.

Adults with cri du chat syndrome

Adults with the syndrome often have short stature. Many develop scoliosis. As adults have not benefited from therapies now available to children with the syndrome, they have poorer communication skills than younger people. Muscle tone usually increases in adults, and they may become spastic. Hyperactivity and concentration problems improve gradually in the years following puberty, particularly in young people who have benefited from early special education.

Diagnosis

The diagnosis is made on the basis of clinical symptoms, and is then confirmed in chromosome or DNA analyses. Traditional chromosome analysis is normally performed by culturing white blood cells (lymphocytes) from a blood test. This method efficiently detects large deletions, visible under a microscope, but may fail to identify the small deletions that sometimes underlie cri du chat syndrome. In these cases, DNA-based analysis is required. Several methods are currently in use, the most common variants being FISH (fluorescent in situ hybridisation) and array comparative genomic hybridization.

If the underlying cause of the 5p deletion is an unbalanced translocation, both parents should be offered genetic screening. If either of them should prove to be a carrier of a balanced translocation, his or her close relations should also be offered genetic screening, as they may also be carriers.

Once the diagnosis is confirmed, the family should be offered genetic counselling. Prenatal diagnosis is available through chorionic villus sampling (placental biopsy, from week 10) or amniocentesis, in which amniotic fluid is drawn from the uterus (from weeks 14-15).

Treatment/interventions

Complications associated with the syndrome can be treated, and a great deal can be done to support and compensate for functional disabilities. Evaluation and follow up of patients with cri du chat syndrome comprise a number of medical examinations. Owing to the diversity of symptoms, it may be necessary for the patient to see many different specialists and therapists. People with the syndrome should be monitored regularly by physicians specialising in neurology and rehabilitation.

Specialist neonatal care may be needed, and sometimes newborns require respiratory assistance. Low birth weight and sucking difficulties are common, and many babies with the syndrome require nasogastric tube feeding. As some children have congenital heart defects, a cardiac ultrasound examination (echocardiogram) should be performed. A paediatric cardiologist will plan interventions as appropriate, and some heart complications may require surgery. Children with heart abnormalities should be monitored regularly.

Palate evaluation should be carried out early. Cleft palate repair may require several surgical interventions.

The child's growth curve should be carefully monitored. A dietician may provide useful advice to counteract constipation problems and may also be able to assist in improving feeding routines. A speech therapist can give advice on how to feed children who have trouble sucking, masticating and swallowing. Sometimes special bottles or other eating aids may be provided. The child may also benefit from oral motor exercise and massage to improve his or her eating abilities. If the feeding problems are severe to the extent that the child requires tube feeding for long periods of time, nutrition may be provided through a gastric feeding tube, inserted through the abdominal wall and into the stomach (percutaneous endoscopic gastrostomy, PEG).

The child should be examined by an ophthalmologist. Some children will need eyeglasses. Strabismus is treated by having the child wear a patch over the unaffected eye, so that the squinting eye is trained.

Ear examination and an audiological evaluation should be performed at an early stage.

When the child suffers from serious sleeping problems, tranquilizing medication may temporarily be used to break a vicious circle. It is also important to develop routines that help the child feel secure.

Motor training and breathing exercises improve the ability of the child to breathe and to cough, thus making it easier to remove mucous from the respiratory system.

Prophylactic dental care is important, as there is an increased risk of cavities and gingivitis. Bite problems should be treated by an orthodontist. For children with congenital heart defects, antibiotic treatment should always be considered in conjunction with dental interventions, owing to the risk of cardiac infections caused by oral bacteria entering the bloodstream.

Drooling problems may be treated by a dentist, a speech therapist or a physiotherapist, depending on the underlying cause. Common causes of drooling include breathing through the mouth, bite defects, muscle laxity and/or loss of feeling. Sucking on teeth or objects stimulate saliva production. Medical treatment or surgery may reduce saliva production and thus check drooling. The potential benefits of surgical intervention can be discussed with an ear, nose and throat specialist.

Treatment and training

Early contact should be established with a paediatric treatment and training team consisting of professionals from various disciplines, all experienced in working with disabilities. The full evaluation of the child's development includes assessments by a psychologist, speech therapist, physiotherapist and an occupational therapist.

Physiotherapy may prevent malpositioned or stiff joints resulting from muscle laxity and delayed motor development. Later, these children often become slightly spastic and develop motor coordination problems, which can also be counteracted with physiotherapy. Balance is often poor, and special equipment may be useful when the child is learning to walk, for example a baby walker, a specially adapted standing frame and/or a rollator. An occupational therapist or a physiotherapist can provide advice and practical assistance. Swimming or riding are good forms of exercise to improve balance and muscle coordination. Fine motor skills should also be practiced.

Social and educational interventions

Early access to special education gives the child the best possibilities of realizing his or her developmental potential. A play therapy centre provides access to special toys and educational material, and is a source of good ideas and guidance. Fun and stimulating activities include water games, playing out of doors, and music therapy.

Routines and a well-structured daily life help the child feel safe and secure, thereby reducing hyperactivity and improving concentration. A psychologist or a specialized learning support teacher may provide advice and assistance in dealing with negative behavioural patterns.

If these children attend day care they may need support in the form of a resource person. When selecting a school, it is important to take the child's individual capacities and limitations into account. Special education will always be needed, and these children often attend schools for children with special educational needs. An after-school facility with small groups and a quiet environment will facilitate concentration.

With encouragement and stimulation, children with the syndrome may be able to fully realize their potential. They may learn to dress and undress themselves, eat unaided, use the toilet and other practical life skills.

All parents should be offered psychological and social support from a psychologist or a guidance counsellor in the primary healthcare services or at a treatment and training centre. Information should be given about community resources and the parents must be given time to ask questions and ventilate their concerns. Many families use respite care services to find an opportunity for valuable rest and recreation. The child may then remain in the home with a personal assistant, or stay with a support family or at a short-term respite care facility. The family may also need assistance in coordinating various interventions and activities.

Language and communication

As children with cri du chat syndrome often understand more than they can express, it is particularly important to offer individually adapted alternative methods of communication, such as sign language or visual symbols. If communication skills are achieved, behavioural problems may be alleviated, or even disappear. In addition to communication practice, these children should be given oral motor exercises to stimulate and facilitate their speech acquisition. A speech therapist can design a program for speech, language and communication training, adapted to the individual child.

Adults with cri du chat syndrome

Adults with the syndrome require continued support from a treatment and training team. Special housing may be needed, for example in the form of group homes or housing with special services for the disabled. Meaningful occupation and assistance in organizing daily activities are important.

Practical advice

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National and regional resources in Sweden

The local county council paediatric clinic/ treatment and training services may contact the regional rehabilitation services and/or the Swedish Centre for Children and Adolescents with Deformities or Syndromes, Uppsala University Children's Hospital, SE-751 85 Uppsala, Sweden. Tel +46 18 611 59 42, or +46 18 611 30 90.

Specialist knowledge in orofacial problems (problems associated with the mouth and face) is available at the Mun-H-Center, Faculty of Odontology, Göteborg University. Address: Medicinaregatan 12A, SE-413 90 Göteborg, Sweden. Tel +46 31 750 92 00, fax +46 31 750 92 01, email: mun-h-center@vgregion.se, Internet: www.mun-h-center.se

Resource personnel

Professor Göran Annerén, Department of Clinical Genetics, The Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel +46 18 611 59 42, email: goran.anneren@akademiska.se

Courses, exchanges of experience, recreation

The Ågrenska Centre arranges stays for children and young people with disabilities and their families, and it is particularly attentive to the needs of people with rare diseases. The Centre is located on the outskirts of Göteborg, and is open to families from all over Sweden. For information, please contact the Ågrenska Centre, Box 2058, SE-436 02 Hovås, Sweden. Tel +46 31 750 91 00, fax +46 31 91 19 79, email: agrenska@agrenska.se, Internet: www.agrenska.se.

The Folke Bernadotte Home arranges theme weeks for families who have children with chromosomal aberrations. Address: Uppsala University Children's Hospital, SE-751 85 Uppsala, Sweden. Tel +46 18 56 42 01, fax +46 18 30 16 35.

Organizations for the disabled/patient associations

The Swedish Cri du Chat Association, email criduchat@telia.com, Internet: www.criduchat.com. Liaison officers: Kalle Eriksson, Kodammsvägen 13, SE-451 91 Uddevalla, Sweden, tel +46 522 856 79, email: kodammen@telia.se.
Anna Killander, tel +46 8 753 66 81, email: anna.killander@telia.com.

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities. Visiting address: Gävlevägen 18B, 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, Internet: www.fub.se.

Courses, exchanges of experience for personnel

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Research and development (R&D)

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Information material

An information booklet on cri du chat syndrome, which summarises 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 1997-126-1022). 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.

Literature

Boraz RA. Cri du Chat syndrome: dental considerations and report of case. Special care in Dentistry 1990; 13.

Cerruti Mainardi P, Guala A, Pastore G, Pozzo G, Dagna Bricarelli F, Pieduigi M. Psychomotor development in Cri du Chat Syndrome. Clin Genet 2000; 57: 459-461.

Mainardi PC, Perfumo C, Cali A, Coucorurde G, Pastore G, Cavani S et al. Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation. J Med Genet 2001; 38: 151-158.

Hall RK. Pediatric Orofacial Medocone and Pathology. Chapmans & Hall 1994.

Howard RO. Ocular abnormalities in the Cri du Chat syndrome. Am J Ophtalmol 1972; 73: 949-952.

Kjaer I, Niebuhr E. Studies of the cranial base in 23 patients with cri-du-chat syndrome suggest a cranial developmental field involved in the condition. Am J Med Genet 1999; 82: 6-14.

Lejeune J, Lafourcade J, Berger R, Vialette J, Roeswillwald M, Seringe P et al. Trois cas de délétion partielle du bras court d'un chromosome 5. C R Acad Sci (Paris) 1963; 257: 3098-3102.

Marinescu C, Johnson EI, Chen X-N, Overhauser J. FISH analysis of terminal deletions in patients diagnosed with cri-du-chat syndrome. Clin Genet 1999; 56: 282-288

Niebuhr E. The Cri du Chat syndrome. Epidemiology, cytogenetics and clinical features. Hum Genet 1978; 44: 227-235.

Overhauser J, McMahon J, Oberlender S, Carlin ME, Niebuhr E, Wasmuth JJ et al. Parental origin of chromosome 5 deletions in the Cri du Chat syndrome. Am J Med Genet 1990; 37: 83-86.

Perfumo C, Cerruti Mainardi P, Cali A, Coucourde G, Zara F, Cavani S et al. The first three mosaic cri du chat syndrome patients with two rearranged cell lines. J Med Genet 2000; 37: 967-972.

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

Van Buggenhout GJCM, Pijkels E, Holvoet M et al. Cri du chat syndrome: changing phenotype in older patients. Am J Med Genet 2000; 90: 203-215.

Zhang A, Zheng C, Hou M, Lindvall C, Li K-J, Erlandsson F et al. Deletion of the telomerase reverse transcriptase gene and haploinsufficiency of telomere maintenance in cri du chat syndrome. Am J Hum Genet 2003; 72: 940-948.

Zhang X, Snijders A, Segraves R, Zhang X, Niebuhr A, Albertson D et al. High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative genomic hybridization. Am J Hum Genet 2005; 76: 312-326.

Database references

OMIM (Online Mendelian Inheritance in Man). Internet: www.ncbi.nlm.nih.gov/omim
search: cri-du-chat 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 emeritus Karl-Henrik Gustavson, Uppsala University Hospital, Sweden.

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

The expert group on rare diseases of the Swedish National Board of Health and Welfare approved the material prior to publication.

Date of publication: 2006-06-26
Version: 3.1
Publication date of the Swedish version: 2006-05-08

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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