Forgotten Diseases Research Foundation

Cri Du Chat Syndrome (CdCS)

Clinical information

Signs and symptoms

Cri du Chat Syndrome, also known as Cat's Cry Syndrome, 5p Minus Syndrome or LeJeune's Syndrome, is a rare genetic disease. According to NIH's Genetics Home Reference (see link at right under General Information), CdCS is thought to occur in one in 15,000 to 50,000 births. It is somewhat more common in females than in males. Roughly 60% of CdCS patients are female, though this figure varies in reported literature (1-3). CdCS occurs in all ethnicities.

The most frequent clinical sign of CdCS is the unusual high-pitched and/or weak cry which gives the syndrome its name. For an example of this unusual feature, see the Multimedia link at the right. This unusual cry is nearly always recognizable at birth. Many of the most common clinical signs of CdCS are neurodevelopmental, as seen in the list below (1). Infants with CdCS may be born prematurely, and are usually small for gestational age. Many patients with CdCS have a distinctive facial appearance, with slanting eyes and a rounded face in infancy, which may change as the child matures. Microcephaly, hypotonia, epicanthal folds, and low-set ears, and retrognathia/micrognathia of the jaw are also common. In most patients, speech is impaired or delayed, and gross motor skills are often delayed or impaired. Patients usually lose the typical cat-like cry during the first two years of life, though they may retain other vocal features such as hoarseness or a weak, high-pitched voice. As patients age, they typically lose the rounded face and develop a narrow, elongated face and more marked microcephaly, as seen in the photo at the right (2), and may develop dental anomalies.

It is important to note that the degree and type of symptoms are extremely variable between affected individuals. Some patients with genetically confirmed CdCS have few of the features which are associated with the disease and may appear nearly phenotypically normal. This fact explains the wide range in estimates of the disease's rate of occurrence.

People with CdCS who have less severe symptoms may not be diagnosed during infancy if the unusual vocal features are not present or not recognized. Behavioral signs, motor delays, and nonspecific intellectual disability or speech impairments, are usually present to some degree even in these patients. Therapeutic interventions in early childhood are thought to have a significant influence on the level of proficiency attained by children with CdCS. Children with CdCS may benefit greatly from interventions intended to improve psychomotor/social skills and communication, so timely diagnosis is important (1, 3). Clinical features that may occur in Cri du Chat Syndrome include the following:

    Common clinical features of cri du chat syndrome

  • Crying that resembles that of a kitten; high-pitched and mewling
  • Hypotonia in infancy (may be severe)
  • Impaired vocalization and/or speech development
  • Intellectual disability, mild to severe
  • Delayed motor milestones, balance problems, falls, and/or clumsiness
  • Rounded face in infancy
  • Elongated face with maturation; may be asymmetric
  • Micrognathia
  • Wide-set eyes
  • Eyes may be markedly slanted in infancy
  • Epicanthal folds in infancy
  • Flattened nasal bridge
  • Tantrums, aggression, and/or self-harming behaviors (hairpulling, biting, or head-banging)
  • Dental/palate abnormalities; high, arched palate and/or dental malocclusions, often anterior open bite
  • Prematuryly grey hair
  • Low birthweight
  • Failure to thrive
  • Feeding/swallowing difficulties and constipation
  • Deformities of the hands; brachydactyly, syndactyly, clinodactyly, and/or single palmar creases
  • Deformities of the feet; pes varus, or talipes deformities (club foot)
  • Ears which are deformed or low-set
  • Hyperacusis (sensitivity to sound in particular frequency ranges)

A number of other problems may also occur in CdCS (1-3). They include congenital heart defects (several types), palate deformities, kidney defects, brainstem abnormalities which may be observed via MRI, hip problems, hypermobile joints or flat feet, sleep disorders, hypogonadism or undescended testicles (in males), hyperactivity, respiratory distress or frequent infections, and abnormal curvatures of the spine (1-3).

Life expectancy with CdCS is usually normal beyond early childhood, though infant mortality is estimated to be as high as 10%, with most (75%) of those infants succumbing to respiratory infections in the first months of life.

Growth charts for Cri du Chat syndrome

Syndrome-specific growth charts exist for CdCS. Please see our Italy page for links to the charts (syndrome-specific growth charts are at the bottom of the page).

Diagnosis and Testing

Most cases of CdCS occur spontaneously (with no family history of the disorder), and are not likely to recur. About 80% of CdCS patients have a deletion of the end of the short arm (p) of chromosome 5. In most of those instances, the mutation occurs early in embryonic development. There are some cases in which a dominant inheritance pattern exists, however. Genetic testing is sometimes required to rule out a heritable defect, which can lead to 50% risk of passing the disease to an affected child's future siblings (3, 4).

CdCS is usually suspected during the first months of life, as over 90% of patients with CdCS have a distinctive pattern of neonatal vocalizations. This distinctive cry may persist in some individuals, but often disappears by age two. In cases where the typical cry is absent, CdCS diagnosis may be delayed because a patient's other features are not distinctive enough to make a diagnosis. This is particularly true in infants and toddlers, where other signs or developmental delays may not yet be apparent.

One important tool in the diagnosis of such patients may be T1-weighted MRI imaging, as shown in the images below. The brainstem, pons, and/or cerebellum of patients with CdCS may show significant hypoplasia in MRI images as compared with age-matched unaffected peers (7).

Many instances of CdCS are the result of deletions that are large enough to be evident on a karyotype, without additional detailed analysis (see sample karyotype of a deletion on chromosome 5 at right; 6). In instances of non-terminal deletions (interstitial deletion, or those in which the phenotype is unusual), additional testing may be advised in order to determine the possible heritability of the mutation.

Differential Diagnosis

While only the unusual cat-like cry is distinctive in CdCS, the combination of features (see list above) tends to result in a unique diagnostic picture, particularly over time. In the absence of the distinctive cat-like cry during infancy, the features of CdCS may resemble several other conditions.

For example, infants with CdCS may have facial features and psychomotor delays that resemble fetal alcohol syndrome (FAS). One difference between the two is that infants with CdCS have shortened philtrums (the groove between the nose and the upper lip), while children with FAS tend to have philtrums that are not only shortened, but unusually smooth, without ridges. Children with fetal alcohol exposure also tend to have shortened/upturned noses. This trait may occur in very young CdCS patient, but it is not usually observed in older children with CdCS.

Children with Cohen syndrome may have hypotonia, failure to thrive, microcephaly, joint hypermobility, and psychomotor delays beginning in infancy, as children with CdCS do. Patients with Cohen Syndrome generally do not exhibit the same pattern of facial dysmorphisms as those with CdCS, and vision problems which are common in Cohen Syndrome are unusual in CdCS.



References

  1. 1. Rodriguez-Caballero A et al. (2010) Cri du chat syndrome: A critical review. Med Oral Patol Oral Cir Bucal 15(3):e473-478. Full text from publisher.
  2. 2. Mainardi PC (2006) Cri du Chat syndrome. Orphanet Journal of Rare Diseases 1:33. doi: 10.1186/1750-1172-1-33. Full text on PubMed.
  3. 3. Sigafoos J et al. (2009) Editorial: Cri-du-Chat. Dev Neurorehabil 12(3):119-121. Abstract on PubMed.
  4. 4. Gu H et al. (2013) A Familial Cri-du-Chat/5p Deletion Syndrome Resulted from Rare Maternal Complex Chromosomal Rearrangements (CCRs) and/or Possible Chromosome 5p Chromothripsis. PLOS ONE 8(10):e76985. doi: 10.1371/journal.pone.0076985. Full text on PubMed.
  5. 5. Weinkove C et al. (1967) The cat-cry syndrome. South African Medical Journal. 11:218-220. Abstract on PubMed.     Full text from Sabinet.
  6. 6. Dangare HM et al. (2012) Cri du chat syndrome: A series of five cases. Ind J Pathol Microbiol 55(4):501-505. Full text from publisher.
  7. 7. Uzunhan TA et al.(2014) A clue in the diagnosis of Cri-du-chat syndrome: Pontine hypoplasia. Ann Indian Acad Neurol 17(2):209-10. Full text on PubMed.




Above: A partial karyotype from a patient with CdCS, showing one copy of chromosome 5 with a deletion of material. See reference 6.







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Above: Facial characteristics of a boy with Cri Du Chat Syndrome showing low-set ears,
strabismus, short philtrum, broad flat nasal bridge, and pronounced hypertelorism, which are
typical of the syndrome. (A, B) Age 4 years, 6 months. (C) Age 11 years, 9 months.
For details, see reference 4.



Below: Left. A sagittal MRI view showing significant brainstem hypoplasia in a 5-month-old
infant with CdCS. Note also the micrognathic jaw and the reduced size of the cranial vault.
Right. A sagittal MRI view showing an age-matched child without CdCS. Note the differences
in the cerebellum, pons, and brainstem in this image compared with the CdCS patient on the left.
For details see reference 7.



Below: A South African infant with CdCS, aged 18 months. Note this child's rounded face,
hypertelorism, downslanting palpebral fissures, epicanthic folds, mild strabismus, short philtrum,
and micrognathism. There is also malformation of the ear. See reference 5.




Page last modified on 20 April 2016.