Cri-du-chat Syndrome 

Updated: Apr 19, 2019
Author: Mithilesh K Lal, MD, MBBS, MRCP, FRCPCH, MRCPCH(UK); Chief Editor: Maria Descartes, MD 



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 the p arm of chromosome 5 (5p) and is characterized by a distinctive, high-pitched, catlike cry in infancy with growth failure, microcephaly, facial abnormalities, and mental retardation throughout life.[2] 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.[3]


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.[4]

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.[5]

A deletion of 5p15.3 results in the manifestation of a catlike cry,[6] whereas a deletion of 5p15.2 results in the presentation of the other major clinical features of the syndrome.[7]  Moreover, a region for speech delay in 5p15.3 has been identified.[8]



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.


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 Sanders et al indicated that symptoms of primary ciliary dyskinesia (PCD), another disorder traced to chromosome arm 5p, are prevalent in patients with cri-du-chat syndrome. Symptoms associated with PCD found in the cri-du-chat syndrome patients included unexplained neonatal distress (35%), year-round nasal congestion that arose in infancy (32%), and a year-round, wet cough that started in infancy (20%).[9]

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.[10]


No racial predilection has been found.


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


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




The following may be noted in the history of patients with cri-du-chat syndrome:

  • Characteristic cry

    • Subtle dysmorphism with neonatal complications and a high-pitched cry typically prompt diagnostic evaluation using cytogenetic studies.

    • Many infants with cri-du-chat syndrome have this distinctive cry, but it is not associated with other aneuploidies.

    • About one third of children no longer exhibit the catlike cry by age 2 years.

  • Developmental history: Early feeding problems are present because of swallowing difficulties; poor suck; failure to thrive; early ear infections; and severe cognitive, speech, and motor delays. Almost all affected individuals have these problems.

  • Behavioral history

    • Behavioral profile includes hyperactivity, aggression, tantrums, stereotypic and self-injurious behavior, repetitive movements, hypersensitivity to sound, clumsiness, and obsessive attachments to objects. Some of these problems are more pronounced in individuals with lower cognitive-adaptive levels and with histories of previous medication trials.

    • Features similar to those of autism and social withdrawal may be more characteristic of individuals who have a 5p deletion due to an unbalanced segregation of a parental translocation. However, children with cri-du-chat syndrome are able to communicate their needs, socially interact with others, and have some degree of mobility.

    • Cornish and Pigram consider an auditory behavioral phenotype, hyperacusis, as a characteristic trait.[11] Hyperacusis is a condition characterized by a hypersensitivity to sound, which causes auditory discomfort, and is reported to be one of the main characteristics of the syndrome.

    • Auditory neuropathy or neural dys-synchrony may be another phenotype of the condition possibly related to abnormal expression of the protein β -catenin mapped to 5p.[12]


Neonatal period

See the list below:

  • Newborns have a characteristic mewing cry, a high-pitched monochromatic cry that is considered pathognomonic for this syndrome.

  • Neonatal complications include poor sucking, need for incubator care, respiratory distress, jaundice, pneumonia, and dehydration.

  • In addition, common findings include the following:

    • Low birth weight

    • Hypotonia

    • Microcephaly

    • Growth retardation

    • Round face with full cheeks

    • Hypertelorism

    • Epicanthal folds

    • Down-slanting palpebral fissures

    • Strabismus

    • Flat nasal bridge

    • Down-turned mouth

    • Micrognathia

    • Low-set ears

    • Short fingers

    • Single palmar creases

    • Cardiac defects (eg, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot

  • Less common findings include the following:

    • Cleft lip and palate

    • Preauricular tags and fistulas

    • Thymic dysplasia

    • Gut malrotation

    • Megacolon

    • Inguinal hernia

    • Dislocated hips

    • Cryptorchidism

    • Hypospadias

    • Rare renal malformations (eg, horseshoe kidneys, renal ectopia or agenesis, hydronephrosis)

    • Clinodactyly of the fifth fingers

    • Talipes equinovarus

    • Pes planus

    • Syndactyly of the second and third fingers and toes

    • Oligosyndactyly

    • Hyperextensible joints


See the list below:

  • Findings include the following:

    • Severe mental retardation

    • Developmental delay

    • Microcephaly

    • Hypertonicity

    • Premature graying of the hair

    • Small, narrow, and often asymmetric face

    • Dropped-jaw, open-mouth expression secondary to facial laxity

    • Short philtrum

    • Malocclusion of the teeth

    • Scoliosis

    • Short third-fifth metacarpals

  • Children with cri-du-chat syndrome also have chronic medical problems such as upper respiratory tract infections, otitis media, severe constipation, and hyperactivity.

Late childhood and adolescence

See the list below:

  • Findings include severe mental retardation, microcephaly, coarsening of facial features, prominent supraorbital ridges, deep-set eyes, hypoplastic nasal bridge, severe malocclusion, and scoliosis.

  • Affected females reach puberty, develop secondary sex characteristics, and menstruate at the usual time. The genital tract is usually normal in females, except for a report of a bicornuate uterus.

  • In males, the testes are often small, but spermatogenesis is thought to be normal.


See the list below:

  • Transverse flexion creases

  • Distal axial triradius

  • Increased whorls and arches on digits


See the list below:

  • Niebuhr, from a review of 331 published cases, estimated that most cri-du-chat syndrome cases are the result of de novo deletions (about 80%), some derive from a familial rearrangement (12%), and only a few show other rare cytogenetic aberrations, such as mosaicism (3%), rings (2.4%), and de novo translocations (3%).[13]

  • Most cases (80-85%) are due to sporadic de novo deletion of 5p (15.3 → 15.2).[14]

  • Approximately 10-15% of cases result from the unequal segregation of a parental balanced translocation in which the 5p monosomy is often accompanied by a trisomic portion of the genome. The phenotypes in these individuals may be more severe than in those with isolated monosomy of 5p because of this additional trisomic portion of the genome.

  • Most cases involve terminal deletions with 30-60% loss of 5p material. Fewer than 10% of patients have other rare cytogenetic aberrations (eg, interstitial deletions, mosaicisms, rings and de novo translocations).

  • Approximately 1-2% of cases have recombinations that involve a pericentric inversion in one of the parents.

  • The occurrence of mosaicism is a very rare finding, with frequency estimated at about 3% of patients. Chromosomal mosaicism has been described and involves a cell line with a 5p deletion and a cell line with a normal karyotype[15] or a 5p deletion with rearranged cell lines.[16]

    G-banded karyotype [46,XX,del(5)(p13)]. G-banded karyotype [46,XX,del(5)(p13)].
    G-banded karyotype of a carrier father [46,XY,t(5; G-banded karyotype of a carrier father [46,XY,t(5;17)(p13.3;p13)].
  • A mechanism that involves dicentric chromosome formation with subsequent breakage and telomere healing during meiosis was recently proposed to explain the rare cases in which a parental paracentric inversion likely results in a viable terminal deletion.

  • The deleted chromosome 5 is paternal in origin in about 80% of cases.

  • Loss of a small region in band 5p15.2 (cri-du-chat critical region) correlates with all clinical features of the syndrome except for the catlike cry, which maps to band 5p15.3 (catlike critical region). The results suggest that 2 noncontiguous critical regions contain genes involved in this condition's etiology.

  • High-resolution mapping of genotype-phenotype relationships in cri-du-chat syndrome using array comparative genomic hybridization (CGH) has provided the following findings:

    • The region associated with the cry was localized to 1.5 Mb in distal band 5p15.31, between bacterial artificial chromosomes (BACs) that contain markers D5S2054 and D5S676.

    • The region associated with the speech delay was localized to 3.2 Mb in band 5p15.32-15.33, between BACs that contain markers D5S417 and D5S635.

    • The region associated with the facial dysmorphology was localized to 2.4 Mb in band 5p15.2-15.31, between BACs that contain markers D5S208 and D5S2887.



Diagnostic Considerations

These include the following:

  • Mental retardation syndromes

  • Multiple congenital anomalies

  • Other autosomal monosomy and trisomy syndromes

Differential Diagnoses



Laboratory Studies

Conventional cytogenetic studies

The size of the 5p deletion may vary from the entire short arm to only 5p15. A small deletion of 5p may be missed using a conventional cytogenetic technique.

High-resolution cytogenetic studies

These look for a small deletion of 5p.

Fluorescence in situ hybridization (FISH)

Molecular cytogenetic studies using FISH allow the diagnosis to be made in patients with very small deletions. FISH uses genetic markers that have been precisely localized to the area of interest.

The absence of a fluorescent signal from either the maternal or paternal chromosome 5p regions indicates monosomy for that chromosomal region.

Fluorescent in situ hybridization (FISH) study of 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).

A rare case of cri-du-chat syndrome born to a woman carrying a t(11;22)(q23;q11.2) has been diagnosed using FISH-based preimplantation genetic diagnosis.[17]

Chromosome comparative genomic hybridization (CGH)

Chromosome CGH is capable of screening the entire genome for DNA copy-number alterations in a single hybridization. The resolution is limited to approximately 5-10 Mb. The results cannot be directly mapped onto the genome sequence.

Microarray CGH

Microarray CGH uses array elements made from large-insert genomic clones, such as BACs and phage artificial chromosomes (PACs).

This method has sufficient measurement precision to permit reliable detection of single-copy aberrations affecting individual clones.

SNP-based test

A study by Wapner et al indicated that a single-nucleotide polymorphism (SNP)-based prenatal test can accurately screen prenatally for cri-du-chat syndrome and other microdeletion syndromes. The study, which employed 358 plasma samples from pregnant women and 111 artificial plasma mixtures, used a massively multiplexed polymerase chain reaction and the Next-generation Aneuploidy Test Using SNPs (NATUS) algorithm. The detection rate for cri-du-chat syndrome was 100% (24 out of 24 samples), with a 0.24% false-positive rate. Detection rates were also 100% for Prader-Willi, Angelman, and 1p36 deletion syndromes and 97.8% for 22q11.2 deletion syndrome.[18]

Imaging Studies

See the list below:

  • Skeletal radiography

    • Microcephaly, retromicrognathia

    • Cranial base malformations (reduced cranial base angle and malformed sella turcica and clivus)

    • Disproportionately short third, fourth, and fifth metacarpals and disproportionately long second, third, fourth, and fifth proximal phalanges (common)

  • MRI

    • Atrophy of the brainstem, atrophic middle cerebellar peduncles and cerebellar white matter

    • Pontine hypoplasia has been described[19]

    • Possible hypoplasia of cerebellar vermis with enlargement of the cisterna magna and fourth ventricle

  • Echocardiography - Used to rule out structural cardiac malformations

Other Tests

See the list below:

  • Swallowing study to assess for feeding difficulty

  • Comprehensive evaluation for receptive and expressive language (Most children have better receptive language than expressive language.)

  • Developmental testing, referral to early intervention, and appropriate school placement


See the list below:

  • Gastrostomy in infancy to protect the airway in patients with major feeding difficulties



Medical Care

Care is supportive. No specific treatment is available for cri-du-chat syndrome.[20]

Genetic counseling is indicated. Female patients are fertile and can deliver viable affected offspring, with an estimated recurrence risk of 50%. Recurrence risk for a de novo case is 1% or less. Rare recurrences in chromosomally healthy parents are probably the result of gonadal mosaicism for the 5p deletion in one of the parents. If a parent is a balanced carrier of a structural rearrangement, the risk is substantially high. The risk should be assessed based on the type of structural rearrangement and its pattern of segregation.

Chronic medical problems such as upper respiratory tract infections, otitis media, and severe constipation require appropriate treatment.

Use the relatively good receptive skills to encourage language and communicative development rather than relying on traditional verbal methods.

Early stimulation and introduction to sign language are effective means of developing communication skills (50% of children are able to use sign language to communicate).

Behavior modification programs may be successful in managing hyperactivity, short attention span, low threshold for frustration, and self-stimulatory behaviors (eg, head-banging, hand-waving).

Visual-motor coordination computerized training improves the visuospatial performance in a child affected by cri-du-chat syndrome.[21]

A study by Guala et al found that individuals with cri-du-chat syndrome appear to benefit from intervention with an educational program developed for such patients. Parents reported social skill improvement in patients who underwent the program, although no differences were found between these patients and those not exposed to the program when analyzed using the Denver Developmental Screening Test II.[22]

Surgical Care

See the list below:

  • Correction of congenital heart defects may be indicated. Medical problems involving minor malformations such as strabismus and clubfoot may be amenable to surgical correction. Orchiopexy may be necessary in patients with undescended testes.

  • Issues important to anesthetic plan include the following:

    • Anatomical abnormalities of the airway

    • Congenital heart disease

    • Hypotonia

    • Mental retardation

    • Temperature maintenance


See the list below:

  • Clinical geneticist

  • Developmental pediatrician

  • Neurologist

  • Cardiologist

  • Ophthalmologist

  • Dentist

  • Orthopedist

  • Psychologist

  • Physical and occupational therapist

  • Speech language pathologist

  • Audiologist

  • Urologist


See the list below:

  • No special diet is required.


See the list below:

  • Activities are limited in patients with profound mental retardation and physical limitations.



Medication Summary

See the list below:

  • Currently, drug therapy is not a component in the standard of care for cri-du-chat syndrome. See Treatment.




See the list below:

  • See Special Concerns for information regarding genetic counseling and prenatal diagnosis in cri-du-chat syndrome.


See the list below:

  • After the first years of life, the mortality (10%) and morbidity rates are low. About 75% of deaths occurred during the first months of life, and as many as 90% occurred within the first year.

  • Recent improvements in management and rehabilitation programs have resulted in increased psychomotor development, improved autonomy, and better social adaptation.

  • Until recently, little was known about the cognitive function of patients with cri-du-chat syndrome. Recent literature indicates that many children can develop some language and motor skills. These children attain the developmental and social skills commonly observed in children aged 5-6 years, although their linguistic abilities are seldom as advanced. Older, home-reared children are usually ambulatory, able to communicate verbally or through sign language, and independent in self-care skills.

Patient Education

See the list below:

  • Families are greatly affected. The main contributor to increased family stress is the child's maladaptive behavior. However, these families also receive social support from other families, friends, and concerned professionals. Up-to-date information about the syndrome and other resources should be made available. The following sources of information are available:

    • National Organization for Rare disorders, Inc. (NORD)

    • PO Box 8923

    • New Fairfield, CT 06812-8923

    • Phone: 800-999-6673

    • Fax: 203-746-6481

    • E-mail:

    • 5p- Society

    • 7108 Katella Avenue #502

    • Stanton, CA 90680

    • Phone: 714-901-1544

    • E-mail:

    • Chromosome Deletion Outreach, Inc. (CDO)

    • PO Box 724

    • Boca Raton, FL 33429-0724

    • Phone: 888-CDO-6880

    • E-mail: