Cri-du-chat Syndrome

Updated: Jun 09, 2017
  • Author: Mithilesh K Lal, MD, MBBS, MRCP, FRCPCH, MRCPCH(UK); Chief Editor: Maria Descartes, MD  more...
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Overview

Background

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 f 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 hyperton Child 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

See the list below:

  • 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 deletion of 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

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.

A study by Lefranc et al indicated that protein-energy malnutrition is a frequent problem in cri-du-chat syndrome, with a review of questionnaires from 36 families revealing evidence of such malnutrition in 47% of patients. [8]

Race

No racial predilection has been found.

Sex

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

Age

The condition is detected in newborns and infants because of the catlike cry and dysmorphic features.

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