What is Cri du Chat Syndrome? [Medically Reviewed]

Overview of the Disorder

Cri du Chat Syndrome (CdCS), also known as 5p- Syndrome, is a rare genetic disorder caused by a deletion of genetic information on the short arm of chromosome 5. The size and position of the deletion vary among individuals, leading to a wide range of symptoms and severity. This disorder was first reported in 1963 by Dr. Jérôme Lejeune, who named it after the distinctive “cat-like cry” observed in infants during early life. The term “Cri du Chat” is French for “cry of the cat.” This high-pitched, monotone cry is particularly noticeable during infancy and gradually diminishes as the child grows. By around age 2, about one-third of children no longer exhibit this characteristic cry.

The estimated incidence of Cri du Chat Syndrome is between 1 in 15,000 and 1 in 50,000 live births, with a higher prevalence in females than males (66% female). In most cases, the syndrome results from a random (de novo) genetic error occurring during early embryonic development and is rarely inherited within families.

Individuals with Cri du Chat Syndrome generally have moderate to severe intellectual disabilities, though some may have only mild intellectual impairments. Many patients demonstrate better receptive language abilities compared to expressive language skills. Although motor coordination is often impaired, recent studies indicate that many children eventually learn to walk. Most patients do not have significant vision or hearing issues, though hypersensitivity to sound can occur.

This syndrome is often associated with various physical and medical complications. Commonly observed problems include scoliosis (curvature of the spine), flat feet, feeding difficulties, gastroesophageal reflux, constipation, respiratory infections, and abnormalities of the kidneys or heart. Regular medical monitoring and appropriate interventions can help minimize the impact of these complications. Hyperactivity, sleep disturbances, and other behavioral challenges are also common but can be managed with a combination of medical and behavioral therapies. Although autism spectrum disorder (ASD) is not strongly linked to Cri du Chat Syndrome, approximately 30% of patients meet the screening criteria for ASD.

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Patients’ Behavioral and Social Characteristics

Patients with Cri du Chat Syndrome may exhibit a variety of social and behavioral traits. In some cases, aggressive behaviors such as self-injury, tantrums, or even psychotic symptoms have been reported, although these do not occur in every individual. On the other hand, individuals with the syndrome are often described as affectionate and sociable, enjoying interactions with others. It is also common for patients to show strong attachment to specific objects or to engage in repetitive behaviors.

Although symptoms and challenges vary widely from person to person, with proper medical care, therapy, and support, patients can achieve developmental milestones and lead fulfilling lives.

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Causes and Diagnostic Methods

Cri du Chat Syndrome (CdCS), also called 5p- Syndrome, is caused by the deletion of genetic material on the short arm of chromosome 5. The critical region involved in this syndrome lies between 5p15.2 and 5p15.3. The size of the deletion varies significantly, from 0.5 megabases (Mb) to 40 Mb. Deletions are classified into three types: “terminal deletions” (most common, occurring at the end of the chromosome), “interstitial deletions” (within the middle of the chromosome), or those caused by unbalanced translocations. About 80% of cases occur spontaneously (de novo) and are not inherited from parents.

Thanks to advances in medical technology, prenatal identification of Cri du Chat Syndrome is now possible. One common method is amniocentesis, which involves sampling amniotic fluid to analyze the fetus’s genetic information. Since amniotic fluid contains fetal cells, this test can detect chromosomal abnormalities such as the deletion on chromosome 5. Amniocentesis is often combined with ultrasound, where detection of physical anomalies in the fetus may raise suspicion of Cri du Chat Syndrome or other genetic disorders.

Although amniocentesis is highly accurate, it carries a small risk of complications, such as miscarriage. Therefore, non-invasive prenatal testing (NIPT) is increasingly recommended. NIPT analyzes fetal DNA circulating in the mother’s blood and is considered a safe and highly precise option that poses no risk to the mother or fetus.

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Postnatal Diagnosis and Genetic Counseling

After birth, Cri du Chat Syndrome may be suspected based on distinctive clinical features. A high-pitched, cat-like cry in the neonatal period is a hallmark sign. Additional symptoms, such as developmental delays or unique facial characteristics, further support the clinical suspicion.

A definitive diagnosis requires genetic testing. Standard methods include karyotype analysis, which uses microscopy to observe chromosomes and confirm the deletion on chromosome 5. More advanced methods, such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), or quantitative polymerase chain reaction (PCR), allow for more detailed analysis of the deletion.

Additional examinations are often performed to assess the extent of complications associated with Cri du Chat Syndrome. For example, X-rays may be used to detect skeletal abnormalities like scoliosis, which is common in affected individuals.

Genetic counseling also plays a critical role in managing this condition. Counseling provides information about the genetic nature of the disorder and advice on the risk of recurrence in future pregnancies. In most cases, the deletion occurs de novo, meaning that the recurrence risk is extremely low. However, in rare cases where a parent carries a balanced translocation—a chromosomal rearrangement—there is a higher risk of recurrence. Although such chromosomal rearrangements typically have no impact on the parent’s health, they can be passed on to the child. It is therefore recommended that parents undergo genetic testing. Research estimates that 0.14% to 0.52% of adults carry a balanced translocation or inversion.

Understanding the diagnostic process and management strategies helps families prepare for providing appropriate care for individuals with Cri du Chat Syndrome.

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Symptoms and Management

Cri du Chat Syndrome (CdCS) presents a broad range of physical, developmental, and behavioral characteristics, with symptom severity varying between individuals.

In the neonatal period, the primary symptoms include low birth weight and microcephaly (a smaller-than-average head circumference). Distinct facial characteristics often include a round face, broad nasal bridge, hypertelorism (wide-set eyes), epicanthal folds, downward-slanting palpebral fissures, downturned corners of the mouth, low-set ears, and micrognathia (small jaw). Abnormal fingerprint patterns and the high-pitched, “cat-like” cry, observed in about 95.9% of newborns, are key diagnostic clues. This cry is believed to result from malformations of the larynx and cranial base during embryonic development.

Newborns frequently experience health problems such as asphyxia, cyanotic episodes, feeding difficulties, and hypotonia (reduced muscle tone). These issues can lead to gastroesophageal reflux and poor nutrition, affecting weight gain during infancy. However, many of these early complications can be managed in neonatal care facilities. Breastfeeding is often possible, and when sucking or swallowing difficulties are present, early physical therapy—initiated within the first few weeks of life—can significantly help.

By the end of the first year, significant psychomotor and intellectual developmental delays usually become evident. Head circumference and weight generally remain below the 2nd or 5th percentile across all age groups. Height is less affected in early childhood but differences become more pronounced during adolescence, especially in males. A slender body habitus in adolescence is also characteristic of Cri du Chat Syndrome.

Rare congenital anomalies, such as cardiac, neurological, or renal malformations, syndactyly (fusion of fingers or toes), hypospadias, cryptorchidism, or preauricular pits, may also be present. Additionally, recurrent respiratory or gastrointestinal infections are common in early childhood, although affected individuals are not inherently more susceptible to infections.

Children with Cri du Chat Syndrome may exhibit hypersensitivity to sound, clumsiness, repetitive behaviors, attachment to specific objects, and self-injurious behaviors. Despite these challenges, many children develop mobility, can communicate their needs, and engage socially. Behavioral assessments emphasize the importance of early intervention to support these abilities.

Although no curative treatment exists, a comprehensive, multidisciplinary approach can significantly improve quality of life. Most neonatal problems can be managed without intensive care. When congenital anomalies are present, early diagnostic evaluation and referral to appropriate specialists are essential. Special attention should also be paid to potential anesthesia-related complications, such as difficult intubation due to laryngeal or epiglottic abnormalities.

Early rehabilitation—including physical, psychomotor, and speech therapy—is crucial for addressing neurological delays. Audiological assessments are recommended for all patients due to the risk of sensorineural hearing loss. Routine vaccinations should also be administered as recommended.

Regular monitoring and individualized interventions help manage feeding difficulties, reflux, and growth parameters. Social and educational support are vital for improving social adaptability and overall well-being. Psychological support for families is also an important component of care, helping them navigate the complexities of the condition.

Behavioral challenges such as hyperactivity, sound hypersensitivity, and repetitive behaviors can be addressed with appropriate behavioral and therapeutic interventions. Promoting social interaction and mobility fosters greater independence and enhances quality of life.

By combining appropriate medical care, rehabilitative services, and psychological support, individuals with Cri du Chat Syndrome can achieve developmental milestones and lead more fulfilling lives.

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Prognosis

Beyond the first few years of life, the survival rate for Cri du Chat Syndrome is high, and serious side effects or adverse reactions related to treatment and disease management are relatively rare. Historically, the mortality rate has been approximately 10%, with 75% of deaths occurring within the first few months of life and up to 90% within the first year.

However, there are reports of individuals surviving into adulthood, even reaching 50 to 60 years of age. With advancements in medical care and therapeutic options, prognosis continues to improve, leading to better quality of life and the potential for longer lifespans.