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Cri-du-chat Syndrome

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Maria Descartes, MD  more...
 
Updated: Apr 21, 2015
 

Background

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  • In 1963, Lejeune et al described a syndrome consisting of multiple congenital anomalies, mental retardation, microcephaly, abnormal face, and a mewing cry in infants with a deletion of a B group chromosome (Bp-), later identified as 5p-.[1]
  • Cri-du-chat syndrome is an autosomal deletion syndrome caused by a partial deletion of chromosome 5p and is characterized by a distinctive, high-pitched, catlike cry in infancy with growth failure, microcephaly, facial abnormalities, and mental retardation throughout life. See the images below.
    Infant with cri-du-chat syndrome. Note the round fInfant with cri-du-chat syndrome. Note the round face with full cheeks, hypertelorism, epicanthal folds, and apparently low-set ears.
    Child with cri-du-chat syndrome. Note the hypertonChild with cri-du-chat syndrome. Note the hypertonicity, small and narrow face, dropped jaw, and open-mouth expression secondary to facial laxity.
  • In recent years, the application of genetic molecular methods introduced advances in the diagnosis and typification of the cri-du-chat syndrome.[2]
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Pathophysiology

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  • A partial deletion of the short arm of chromosome 5 is responsible for the characteristic phenotype.
  • The characteristic cry is perceptually and acoustically similar to the mewing of kittens. This unusual cry is due to structural abnormalities of the larynx (eg, laryngeal hypoplasia) and CNS dysfunction. The laryngeal appearance may be normal or may exhibit marked anatomical abnormalities such as floppy epiglottis, small larynx, and asymmetric vocal cords. However, the cause of the characteristic cry cannot be entirely ascribed to the larynx. A developmental field may connect the brain and the affected clivus region of the cranial base with the laryngeal region from which the characteristic cry derives. This area of the brain is probably deformed in patients with cri-du-chat syndrome. The characteristic cry usually disappears over time.
  • Cri-du-chat syndrome is caused by a partial or total deletionof genetic material on the short arm of chromosome 5. The size of the deletion could affect from region 5p15.3 to the complete loss of the short arm. Most of the cases (approximately 80%) are due to a de novo deletion, a little more than 10% of the cases are originated by a parental translocation, and less than 10% are associated with cytogenetic rare aberrations.[3]
  • Genotype-phenotype studies in cri-du-chat syndrome led to the identification of two separate chromosomal regions, hemizygosity for which is associated with specific phenotypes.[4]
  • A deletion of 5p15.3 results in the manifestation of a catlike cry,[5] whereas a deletion of 5p15.2 results in the presentation of the other major clinical features of the syndrome.[6]
  • Moreover, a region for speech delay in 5p15.3 has been identified.[7]
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Epidemiology

Frequency

United States

  • The estimated prevalence is about 1 in 50,000 live births.
  • The prevalence among individuals with mental retardation is about 1.5 in 1000.

Mortality/Morbidity

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  • With contemporary interventions, the chance of survival to adulthood is possible.
  • Currently, the mortality rate of cri-du-chat syndrome is 6-8% in the overall population.
  • Pneumonia, aspiration pneumonia, congenital heart defects, and respiratory distress syndrome are the most common causes of death.

Race

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  • No racial predilection has been found.

Sex

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  • A significant female predominance is observed in affected newborns, with a male-to-female ratio of 0.72:1.

Age

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  • The condition is detected in newborns and infants because of the catlike cry and dysmorphic features.
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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG Professor, Department of Pediatrics, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

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Infant with cri-du-chat syndrome. Note the round face with full cheeks, hypertelorism, epicanthal folds, and apparently low-set ears.
Child with cri-du-chat syndrome. Note the hypertonicity, small and narrow face, dropped jaw, and open-mouth expression secondary to facial laxity.
Fluorescent in situ hybridization (FISH) study of a patient with cri-du-chat syndrome. FISH photograph shows deletion of a locus-specific probe for the cri-du-chat region. Spectrum orange color represents chromosome 5–specific signal and spectrum green is cri-du-chat locus signal. Absence of a green signal indicates monosomy for that region (left, interphase cell; right, metaphase chromosome spread).
G-banded karyotype [46,XX,del(5)(p13)].
G-banded karyotype of a carrier father [46,XY,t(5;17)(p13.3;p13)].
 
 
 
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