What is Cat Syndrome? Understanding Cri du Chat

Cri du chat syndrome, often referred to as “cat syndrome” due to a distinctive, high-pitched cry in affected infants, is a rare genetic disorder stemming from a missing piece of chromosome 5. This chromosomal deletion leads to a range of developmental challenges and characteristic physical features. This article delves into the intricacies of Cri du chat syndrome, exploring its causes, symptoms, diagnosis, and management strategies, emphasizing the crucial role of a multidisciplinary healthcare team in improving patient outcomes.

Decoding Cri du Chat Syndrome: An Overview

Cri du chat syndrome, aptly named for the French phrase meaning “cry of the cat,” is a genetic condition characterized by a unique, cat-like cry in newborns. This cry, resulting from issues with the larynx and vocal cords, is a hallmark symptom but not the only one. The syndrome is caused by the deletion of genetic material on the short arm (p arm) of chromosome 5. The severity and presentation of Cri du chat syndrome can vary significantly depending on the size and location of the deletion on chromosome 5. Individuals with this syndrome often exhibit distinctive facial features, developmental delays, and intellectual disabilities.

What Causes Cat Syndrome? Etiology of Cri du Chat

Cri du chat syndrome arises from a deletion of a portion of chromosome 5p. In the majority of cases, this deletion occurs spontaneously (de novo) as a random event during the formation of sperm or egg cells, or in early fetal development. Interestingly, in 80% to 90% of de novo cases, the deletion originates from the paternal chromosome. These deletions can occur due to chromosomal breakage during the formation of gametes (reproductive cells).

While most cases are de novo, approximately 10% to 15% of cases are inherited from a parent carrying a balanced translocation. A balanced translocation means the parent has rearranged chromosomes, but no genetic material is lost or gained, so they are unaffected. However, when passing this chromosome arrangement to their child, it can become unbalanced, leading to Cri du chat syndrome.

The type of deletion also varies. Terminal deletions, where the end of chromosome 5p is missing, account for 80% to 90% of cases. Interstitial deletions, where a segment within chromosome 5p is missing, are less common, occurring in 3% to 5% of cases. Rarer mechanisms include mosaicism (where some cells have the deletion and others don’t), inversions, and ring chromosomes.

How Common is Cat Syndrome? Epidemiology

Although considered rare, Cri du chat syndrome is among the more frequently observed chromosomal abnormalities. Its incidence is estimated to range from 1 in 15,000 to 1 in 50,000 live births. Females are slightly more often affected than males. The exact prevalence globally and across different ethnic groups remains undetermined, and specific risk factors linked to prenatal events or parental age are not clearly established. However, some reports suggest potential associations with parental exposure to radiation, severe morning sickness (hyperemesis), anorexia, and toxemia during pregnancy, although these are not confirmed causal links.

Pathophysiology: How Chromosome 5 Deletion Impacts Development

The clinical features of Cri du chat syndrome are linked to the loss of genes on chromosome 5p. Despite variations in the size of the deleted region, research points to a critical region, 5p15.2, as being primarily responsible for the core features of the syndrome when present in only one copy (hemizygosity). Individuals with chromosome 5 deletions that do not include this region may not exhibit the typical Cri du chat phenotype and can even be phenotypically normal in some instances.

Further cytogenetic studies have refined our understanding, identifying sub-regions within 5p15. Specifically, 5p15.3 is associated with the characteristic cat-like cry, while 5p15.2 is linked to other significant clinical features of the syndrome. Other areas within 5p are thought to influence features like speech delay and distinctive facial characteristics.

The hallmark cat-like cry is believed to stem from anatomical differences in the larynx. These may include:

A smaller, more flexible epiglottis
Underdevelopment (hypoplasia) of the larynx
A narrow or diamond-shaped larynx
Unusual airspace in the posterior larynx during sound production

It is important to note that not every infant with an abnormal cry has these laryngeal features, suggesting that neurological factors may also play a role in the distinctive cry. The size and type of deletion, whether terminal or interstitial, also contribute to the variability in how Cri du chat syndrome manifests.

Recognizing Cat Syndrome: History and Physical Examination

Neonatal Period

The most striking sign in newborns is the high-pitched, monotone cry resembling a cat’s meow. This cry often lessens and may disappear within the first few months of life. However, it’s crucial to remember that this cry is not exclusive to Cri du chat syndrome and can be present in other neurological conditions. Infants with Cri du chat syndrome often have low birth weight and microcephaly (smaller head size). They may also experience birth asphyxia, hypotonia (low muscle tone), and difficulties with sucking, leading to feeding challenges and impacting early growth and development. There are also reports of increased susceptibility to respiratory and intestinal infections in infancy.

General Characteristics

Craniofacial Malformations:

Facial features associated with Cri du chat syndrome are often apparent at birth and may evolve over time.

Common Features:

Microcephaly
Round face (“moon face”) in infancy
Hypertelorism (widely spaced eyes)
Prominent epicanthic folds (skin folds at the inner corner of the eyes)
Broad nasal bridge
Down-turned corners of the mouth
Short philtrum (vertical groove between the nose and upper lip)
Premature graying of hair
Single transverse palmar crease (simian crease)

Less Common Features:

Downward slanting palpebral fissures (eye openings slanting downwards)
Low-set ears
Narrow ear canals
Preauricular tags (small skin growths in front of the ears)
Hearing loss (deafness)
Myopia (nearsightedness) and cataracts
Pupil hypersensitivity to methacholine
Hypospadias (in males, urethra opening on the underside of the penis) and cryptorchidism (undescended testicles)

As individuals with Cri du chat syndrome age, some facial characteristics may change:

Hypotonia in infancy may transition to hypertonia (increased muscle tone) later in childhood.
Microcephaly becomes more pronounced.
The supraorbital ridge (brow ridge) may become more prominent.
Dental malocclusion (misalignment of teeth) can develop.
The round “moon face” of infancy may become more elongated and vertically narrow in adulthood.

Other Potential Anomalies:

Hypersensitivity to sounds (hyperacusis)
Cardiac defects, including congenital heart disease
Cutaneous hemangiomas (birthmarks made of blood vessels)
Renal (kidney) abnormalities

Orofacial Abnormalities:

High arched palate
Microretrognathia (small and receding lower jaw)
Enamel hypoplasia (underdeveloped tooth enamel)
Increased risk of chronic periodontitis (gum disease)

Developmental and Behavioral Manifestations:

Individuals with Cri du chat syndrome typically experience intellectual disability and developmental delays. Behavioral traits may include:

Hyperactivity
Self-injurious behaviors
Repetitive movements
Gentle and affectionate personality
Strong attachment to objects
Receptive language (understanding speech) is often better than expressive language (ability to communicate verbally).

Diagnosis: Identifying Cat Syndrome

Prenatal Diagnosis

Cri du chat syndrome can be detected prenatally through amniocentesis, a procedure where amniotic fluid surrounding the fetus is sampled. Chromosome analysis (karyotyping) of fetal cells can reveal the 5p deletion. Prenatal ultrasound may also detect structural abnormalities associated with the syndrome. In cases of mosaicism, fetal chromosome analysis from amniotic fluid or placental samples may show chromosomal abnormalities, along with findings like microcephaly and cerebellar hypoplasia on ultrasound.

Postnatal Diagnosis

After birth, diagnosis is often suspected based on the characteristic clinical features. The combination of microcephaly, low birth weight, round face, hypotonia, and the distinctive cat-like cry should raise suspicion for Cri du chat syndrome. However, the phenotypic variability due to different deletion sizes and locations can sometimes make clinical diagnosis challenging.

If Cri du chat syndrome is suspected, karyotype analysis is usually the first diagnostic test to confirm the 5p deletion. In situations where clinical suspicion is high but the karyotype is normal (which is rare in typical deletions, but could occur in mosaicism or very subtle deletions), more specialized genetic tests can be used. These include:

Fluorescence in situ hybridization (FISH): This technique uses fluorescent probes to detect specific DNA sequences, including the 5p deletion.
Comparative genomic hybridization (CGH): CGH allows for a broader analysis of the genome to identify gains or losses of chromosomal material.
Quantitative polymerase chain reaction (PCR): PCR can be used to quantify specific DNA sequences and detect deletions.

FISH has significantly improved the diagnosis of deletion syndromes like Cri du chat, allowing for more precise mapping of deletions and genotype-phenotype correlations. CGH and microarray analysis offer even more comprehensive genomic screening capabilities.

Magnetic Resonance Imaging (MRI) studies in Cri du chat syndrome are limited. However, pontine hypoplasia (underdevelopment of the pons, part of the brainstem) appears to be a relatively common finding. This may be associated with other brain abnormalities such as cerebellar hypoplasia, microcephaly, and corpus callosum anomalies. Supratentorial brain abnormalities have also been reported.

Treatment and Management of Cat Syndrome

Currently, there is no cure for Cri du chat syndrome as the genetic deletion occurs early in development, impacting brain formation. Management focuses on addressing the various symptoms and maximizing the individual’s potential through supportive therapies and early intervention. Early intervention programs are crucial for improving prognosis and promoting social adaptation.

During the newborn period, physical therapy should commence within the first week of life to address feeding difficulties like swallowing and sucking. Breastfeeding is often possible, and intensive care is typically not required unless there are significant complications.

Ongoing therapies and interventions include:

Physical therapy: To address motor delays and hypotonia.
Occupational therapy: To improve fine motor skills, daily living skills, and sensory processing.
Speech therapy: To address speech and language delays, and communication skills.
Psychomotor therapy: To integrate physical, emotional, and cognitive development.
Audiological evaluations: Due to the risk of sensorineural hearing loss, regular hearing tests are recommended.

Other management strategies may include surgery for congenital heart defects or other structural anomalies, specialized diets if needed for feeding difficulties, and establishing consistent daily routines. Family involvement is paramount, and providing families with comprehensive information about Cri du chat syndrome and connecting them with support groups is essential. Genetic counseling should be offered to families to discuss recurrence risks in future pregnancies.

Differential Diagnosis: Conditions to Consider

When diagnosing Cri du chat syndrome, it’s important to consider other conditions that may share similar features, especially in infancy. These include:

Multiple congenital anomaly syndromes: A broad category of syndromes with various birth defects.
Other autosomal monosomies or trisomies: Other chromosomal disorders involving missing or extra chromosomes.
Other intellectual disability syndromes: Syndromes primarily characterized by intellectual disability.
Patau syndrome (Trisomy 13)
Wolf-Hirschhorn syndrome (4p deletion syndrome)

Prognosis for Individuals with Cat Syndrome

The prognosis for individuals with Cri du chat syndrome varies. Mortality rates are highest in the first few years of life, with approximately 75% of deaths occurring within the first month and around 90% within the first year. However, morbidity and mortality rates decrease significantly after infancy. The extent and location of the chromosomal deletion are significant factors influencing prognosis. Early diagnosis is crucial as it allows for timely implementation of therapeutic interventions to optimize physical and psychomotor development and improve social adaptation. With appropriate support and intervention, many individuals with Cri du chat syndrome can live well into adulthood and achieve meaningful milestones.

Potential Complications of Cri du Chat Syndrome

Individuals with Cri du chat syndrome are at risk for various complications, including:

Congenital heart defects: Heart abnormalities present at birth.
Other organ defects: Anomalies in other organ systems.
Scoliosis: Curvature of the spine.
Poor muscle tone: Hypotonia can persist and affect motor skills.
Hearing and visual impairments: Hearing loss and eye problems.
Intellectual disability: Varying degrees of intellectual disability are a core feature.

Deterrence and Patient Education: Supporting Families

Beyond the challenges faced by individuals with Cri du chat syndrome, their families also experience significant stress. Providing support to both patients and families is crucial. This includes emotional support from healthcare providers, connecting families with peer support networks, and offering respite care when needed. Educating families about the syndrome, its management, and available resources empowers them to advocate for their child and navigate the challenges effectively.

Key Facts about Cri du Chat Syndrome

Cri du chat syndrome is a rare genetic disorder caused by a deletion on chromosome 5p.
Phenotype variability is linked to genotype variations, impacting symptom severity and prognosis.
The characteristic cat-like cry is a hallmark symptom, along with microcephaly, low birth weight, hypotonia, developmental delays, and distinctive facial features.
Clinical diagnosis is possible, but karyotype analysis confirms the 5p deletion. Advanced genetic testing (FISH, CGH) can be used in cases with high clinical suspicion and normal karyotype.
Management focuses on early intervention and rehabilitation, including physical, occupational, and speech therapy, to improve prognosis and social adaptation.
Mortality is highest in early infancy, but with appropriate care, many individuals live into adulthood.

Enhancing Healthcare Team Outcomes

Effective management of Cri du chat syndrome requires a collaborative interprofessional team. This team typically includes:

Nurses: For ongoing care, monitoring, and family support.
Physicians (Genetics, Pediatrics, Neurology, Cardiology, etc.): For diagnosis, medical management, and addressing specific health concerns.
Therapists (Physical, Occupational, Speech): For rehabilitation and developmental interventions.
Social workers: To connect families with resources and support services.
Dietitians: To address nutritional needs and feeding challenges.

Early intervention and coordinated care are essential to optimize outcomes for individuals with Cri du chat syndrome and their families. By working together, the interprofessional team can provide comprehensive, holistic care that addresses the complex needs of these patients and enhances their quality of life.

Go to Multiple Choice Questions on Cri du Chat Syndrome

References

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