Handbook of Genetic Counseling/Cri-du-chat syndrome - deletion 5p

Cri-du-chat syndrome - deletion 5p

Contracting

Introduction
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Interim History

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Cri du chat is a syndrome that is associated with a deletion of the short arm of chromosome 5
French for "cat's cry"
incidence is 1:50,000 (Van Buggenout et al., 2000 ) may be as high as 1:20,000 (OMIM)

Characteristic features

usually suspected at birth based on characteristic monochromatic, high-pitched cry
poor suck, vomiting, failure to thrive, respiratory distress and jaundice present in 60-92%
microcephaly
round face
hypertelorism
epicanthal folds
down-slanting palpebral fissures
low-set ears
micrognathia
psychomotor retardation
high arched palate
- as individuals with 5p deletion get older change of phenotype is noted and it is less striking and harder to diagnose (face lengthens, face becomes "coarse", prominent supra-orbital ridges, deep-set eyes, hypoplastic nasal bridge, severe dental malocclusion, relatively large mouth, and full lower lip)

Potential health problems

several cardiac anomalies described in a small number of patients (ASD, VSD, tetralogy of fallot and PDA)
cleft palate (rare)
gastrointestinal abnormalities include malrotation and Hirschprung disease
teeth abnormally erupted
Apnea
Strabismus
Minor vision problems
Gastric reflux
Chronic constipation (well managed in most cases)
Colic
Frequent ear and upper respiratory infections
Scoliosis
Sleep disorders
Saliva control problems (if not resolved during childhood surgery can help correct)
Minor hearing impairment

Growth

compared with the standard population, most children with cri-du-chat syndrome are small at birth
as they grow most have significant microcephaly
weight compromised for age
slow growth frequently observed
may be evidence of intrauterine growth retardation

Life expectancy

Difficult to predict
10% mortality in first year due to respiratory or cardiac complications
Believed that if no major health problems present life span would be in normal range

Learning

study of 26 children ages 6 yr. 4 mths and 15 yr 5 mths
- moderate to severe learning difficulties and developmental delay are usually observed
- 24 were in severe learning disability range
- better receptive than expressive language
study of seven patients
- 6 severe or profound MR
- 1 mild MR
Language comprehension may not be as impaired as language production
Clear benefit shown in those children that received early intervention services compared to those that did not
- Developed many self-care skills
- Communicate through short sentences, words, signs, or gestures

Behavior

study examined the range, distinctiveness, and correlates of maladaptive behavior in 146 subjects using the Aberrant *Behavior Checklist as a standardized measure
- Hyperactivity was the most significant and frequent problem in the sample
- Subjects also showed aggression, tantrums, self-injurious behavior
- some of these problems were more pronounced in individuals with lower cognitive-adaptive levels, as well as in those with histories of previous medication trials
- Autistic-like features and social withdrawal were more characteristic of individuals with translocations as opposed to deletions, even when controlling for the lower adaptive level of the translocation group
- head banging, hitting the head against body parts, self-biting and rumination are the most frequently occurring behaviours in CCS
- Aggressive behaviour was reported for 88%, with a statistically significant negative correlation between age and the number of aggressive behaviors reported
Study of 7 older patients most had periods of destructive behavior, self mutilation and aggression
Other reported behaviors include:
- Repetitive movements
- Obsessive attachment to objects
- Hypersensitivity to sensory stimuli
- Feeding and sleeping problems
- Mood disorders

Genetics

85% are sporadic deletions *10-15% are familial (usually parental translocation rarely a familial inversion)
PARENTAL CHROMOSOMES SHOULD BE DONE SO ACCURATE RECURRANCE RISKS CAN BE CALCULATED
Gene that makes Delta-catenin (an adherends junction protein involved in cell motility and expressed early in neuronal development)
delta-catenin maps to a specific region in 5p15.2 that has been implicated in the mental retardation phenotype
strong correlation between the hemizygous loss of delta-catenin and severe mental retardation

Genotype-phenotype correlation

Patients show phenotypic and cytogenetic variability
Genotype-phenotype correlation in 62 patients with terminal deletions highlighted a progressive severity of clinical manifestation and psychomotor retardation related to the size of the deletion (Mainardi et al., 2001). Whereas other study reported no correlation with size of deletion and severity in 50 patients (Marinescu et al., 1999).
The analysis of seven patients with interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3
study lends support to the hypothesis of a separate region in p15.3 for the speech delay
One family with deletion 5p where breaking point is slightly distal to 15.3 showed only

Patient resources/ references

5p- Society (Cri-du-Chat) -- support group

11609 Oakmont

Overland Park, KS 66210

Phone: (913) 469-8900

E-mail: fivepminus@aol.com

Web Site: http://www.fivepminus.org/

Conference in SLC Aug 15-19, 2002

Chromosome Deletion Outreach

P.O. Box 724

Boca Raton, FL 33429-0724

E-mail: cdo@worldnet.att.net

Web site:members.aol.com/cdousa/cdo.htm

Cri Du Chat Support Group of Australia Inc.

Email: info@criduchat.asn.au <mailto:info@criduchat.asn.au>

Web: http://www.criduchat.asn.au

References

Mainardi, P C; Perfumo, C; Cali, A; Coucourde, G; Pastore, G; Cavani, S; Zara, F; Overhauser, J; Pierluigi, M; Bricarelli, F D. Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation. JOURNAL OF MEDICAL GENETICS. vol. 38, no. 3 (2001 Mar): 151-8.
Collins, M S Ross; Cornish, K. A survey of the prevalence of stereotypy, self-injury and aggression in children and young adults with Cri du Chat syndrome. JOURNAL OF INTELLECTUAL DISABILITY RESEARCH. vol. 46, no. Pt 2 (2002 Feb): 133-40.
Medina, M; Marinescu, R C; Overhauser, J; Kosik, K S. Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome. GENOMICS. vol. 63, no. 2 (2000 Jan 15): 157-64.
Cornish, K M; Cross, G; Green, A; Willatt, L; Bradshaw, J M. A neuropsychological-genetic profile of atypical cri du chat syndrome: implications for prognosis. JOURNAL OF MEDICAL GENETICS. vol. 36, no. 7 (1999 Jul): 567-70.
Marinescu, RC, et al. No relationship between the size of the deletion and level of developmental delay in cri-du-chat syndrome. AMERICAN JOURNAL OF MEDICAL GENETICS. vol. 86, no. 1 (1999 Sep 3): 66-70.
Cornish, K M; Bramble, D; Munir, F; Pigram, J. Cognitive functioning in children with typical cri du chat (5p-) syndrome. DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. vol. 41, no. 4 (1999 Apr): 263-6.
Van Buggenhout, G.J.C.M. et al. Cri du Chat Syndrome: Changing Phenotype in Older Patients. AMERICAN JOURNAL OF MEDICAL GENETICS. 90:203-215 (2000).

Notes

The information in this outline was last updated in 2002.