Cri-du-chat syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size (microcephaly), low birth weight, and weak muscle tone (hypotonia) in infancy. Affected individuals also have distinctive facial features, including widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Cri-du-chat syndrome is caused by a deletion of the end of the short (p) arm of chromosome 5. This chromosomal change is written as 5p-. The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in more severe intellectual disability and developmental delay than smaller deletions.

The signs and symptoms of cri-du-chat syndrome are probably related to the loss of multiple genes on the short arm of chromosome 5. Researchers believe that the loss of a specific gene, CTNND2, is associated with severe intellectual disability in some people with this condition. They are working to determine how the loss of other genes in this region contributes to the characteristic features of cri-du-chat syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of cri-du-chat syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.

About 10 percent of people with cri-du-chat syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with cri-du-chat syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 5, which results in the intellectual disability and health problems characteristic of this disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Cri-du-chat syndrome occurs in an estimated 1 in 20,000 to 50,000 newborns. This condition is found in people of all ethnic backgrounds.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormally high-pitched voice · Very frequent (99-80%)

A persistent (minutes to hours) abnormal increase in the pitch (frequency) of the voice for the context or social situation or significantly different from baseline of the individual.

Cat cry · Very frequent (99-80%)

The presence of a characteristic high-pitched cry that sounds similar to the meowing of a kitten.

Epicanthus · Very frequent (99-80%)

A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus.

Hypotonia · Very frequent (99-80%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Intellectual disability, severe · Very frequent (99-80%)

Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34.

Microcephaly · Very frequent (99-80%)

Head circumference below 2 standard deviations below the mean for age and gender.

Microretrognathia · Very frequent (99-80%)

A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.

Posteriorly rotated ears · Very frequent (99-80%)

A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).

Round face · Very frequent (99-80%)

The facial appearance is more circular than usual as viewed from the front.

Severe global developmental delay · Very frequent (99-80%)

A severe delay in the achievement of motor or mental milestones in the domains of development of a child.

Wide nasal bridge · Very frequent (99-80%)

Increased breadth of the nasal bridge (and with it, the nasal root).

Abnormality of the voice · Very frequent (99-80%)

Downslanted palpebral fissures · Frequent (79-30%)

The palpebral fissure inclination is more than two standard deviations below the mean.

High palate · Frequent (79-30%)

Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).

Other findings in the same source

From: Orphanet

Additional reported features include Hypertelorism (Frequent (79-30%)); Intrauterine growth retardation (Frequent (79-30%)); Scoliosis (Frequent (79-30%)); Short neck (Frequent (79-30%)); Short stature (Frequent (79-30%)); Small hand (Frequent (79-30%)); Abnormal cardiovascular system morphology (Occasional (29-5%)); Abnormality of bone mineral density (Occasional (29-5%)); Finger syndactyly (Occasional (29-5%)); Inguinal hernia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Cri-du-chat syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Cri-du-chat syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.