Cri-du-chat Syndrome

Overview

Plain-Language Overview

Cri-du-chat syndrome is a rare genetic disorder caused by a missing piece of chromosome 5. It is named for the distinctive high-pitched cry of affected infants, which sounds like a cat. Children with this condition often have delayed development, intellectual disability, and unique facial features such as a small head and wide-set eyes. Many also experience problems with feeding and breathing early in life. The syndrome affects each person differently, but it generally leads to lifelong challenges with learning and physical growth.

Clinical Definition

Cri-du-chat syndrome is a congenital disorder resulting from a partial deletion of the short arm of chromosome 5 (5p deletion). It is characterized by a distinctive high-pitched, cat-like cry in infancy due to abnormal development of the larynx and nervous system. Affected individuals typically present with microcephaly, hypertelorism, epicanthal folds, and a round face. Intellectual disability ranges from moderate to severe, accompanied by delayed psychomotor development. Additional features include hypotonia, feeding difficulties, and growth retardation. The syndrome is caused by haploinsufficiency of multiple genes within the deleted region, including the critical region 5p15.2. Diagnosis is confirmed by cytogenetic analysis such as karyotyping or fluorescence in situ hybridization (FISH). The condition occurs sporadically in most cases but can be inherited from a parent with a balanced translocation. Management is supportive and multidisciplinary, focusing on developmental therapies and medical complications.

Inciting Event

The inciting event is a de novo deletion of the short arm of chromosome 5 during gametogenesis or early embryogenesis.
In some cases, the deletion results from a parental balanced translocation leading to unbalanced chromosomal material in the child.

Latency Period

none

Diagnostic Delay

Mild or atypical presentations can lead to delayed recognition of the syndrome.
Lack of awareness of the characteristic cry and dysmorphic features may delay diagnosis.
Limited access to genetic testing in some settings contributes to diagnostic delay.

Clinical Presentation

Signs & Symptoms

Distinctive high-pitched cry resembling a cat's meow.
Severe intellectual disability and developmental delay.
Microcephaly and characteristic facial dysmorphisms.
Hypotonia and poor feeding in infancy.
Delayed speech and motor milestones.

History of Present Illness

Infants present with a distinctive high-pitched, cat-like cry shortly after birth.
Developmental delay and intellectual disability become apparent in early childhood.
Feeding difficulties and poor growth are common in infancy.
Characteristic facial features include microcephaly, hypertelorism, and a round face.

Past Medical History

none

Family History

A family history of chromosomal abnormalities or balanced translocations may be present.
Parents may be asymptomatic carriers of balanced translocations involving chromosome 5.
No consistent pattern of inheritance; most cases are sporadic.

Physical Exam Findings

Characteristic high-pitched, cat-like cry in infancy.
Microcephaly with a round face and hypertelorism.
Downward slanting palpebral fissures and epicanthal folds.
Micrognathia and low-set ears.
Hypotonia and delayed motor development.

Diagnostic Workup

Diagnostic Criteria

Diagnosis of Cri-du-chat syndrome is based on the presence of a characteristic high-pitched cry in infancy, distinctive craniofacial features including microcephaly and hypertelorism, and developmental delay. Confirmation requires cytogenetic testing demonstrating a deletion on the short arm of chromosome 5 (5p deletion) via karyotype or FISH analysis. Additional supportive findings include hypotonia, feeding difficulties, and growth retardation.

Pathophysiology

Key Mechanisms

Cri-du-chat syndrome results from a deletion of the short arm of chromosome 5 (5p-).
The loss of genetic material leads to abnormal development of the larynx and nervous system, causing the characteristic high-pitched cry and intellectual disability.
Haploinsufficiency of genes such as CTNND2 and SEMA5A contributes to the neurological and developmental abnormalities.

Involvement	Details
Organs	Brain is affected leading to intellectual disability and developmental delay.
	Larynx abnormalities cause the characteristic high-pitched cry.
	Heart may have congenital defects associated with the syndrome.
Tissues	Brain tissue shows structural abnormalities contributing to cognitive impairment.
Tissues	Laryngeal tissue abnormalities cause the distinctive cat-like cry.
Cells	Neurons are affected leading to intellectual disability and developmental delay.
Cells	Laryngeal cells contribute to the characteristic high-pitched cry due to abnormal development.
Chemical Mediators	Neurotransmitters such as dopamine and serotonin may be involved in neurodevelopmental abnormalities.

Treatment

Pharmacological Treatments

none
- Mechanism: none
- Side effects: none

Non-pharmacological Treatments

Early intervention programs improve developmental outcomes through specialized therapies.
Speech therapy assists in improving communication skills affected by the syndrome.
Physical therapy helps enhance motor skills and muscle strength.
Occupational therapy supports daily living skills and adaptive behaviors.

Prevention

Pharmacological Prevention

none

Non-pharmacological Prevention

Genetic counseling for at-risk parents to prevent recurrence.
Prenatal diagnosis via chorionic villus sampling or amniocentesis to detect 5p deletion.

Outcome & Complications

Complications

Severe intellectual disability impacting quality of life.
Feeding difficulties leading to malnutrition.
Respiratory infections due to hypotonia and poor airway protection.

Short-term Sequelae	Long-term Sequelae
Poor feeding and failure to thrive in infancy. Recurrent respiratory infections due to hypotonia.	Persistent severe intellectual disability and developmental delays. Chronic behavioral and psychiatric issues. Growth retardation and physical disabilities.

Differential Diagnoses

Cri-du-chat Syndrome versus Angelman Syndrome

Cri-du-chat Syndrome	Angelman Syndrome
High-pitched, cat-like cry in infancy is pathognomonic.	Ataxic gait and frequent laughing episodes are characteristic.
Distinctive facial features including round face and hypertelorism.	Severe speech impairment with better receptive language skills.
Severe intellectual disability with delayed psychomotor development.	Microcephaly develops after infancy.

Cri-du-chat Syndrome versus Down Syndrome

Cri-du-chat Syndrome	Down Syndrome
Characteristic cat-like cry due to laryngeal abnormalities.	Upward slanting palpebral fissures and epicanthal folds.
Microcephaly and round face with hypertelorism.	Simian crease on the palm and hypotonia.
Deletion of short arm of chromosome 5 detected by FISH.	Trisomy 21 confirmed by karyotype analysis.

Cri-du-chat Syndrome versus Williams Syndrome

Cri-du-chat Syndrome	Williams Syndrome
Cat-like, high-pitched cry in infancy.	Elfin facies with a broad forehead and full cheeks.
Microcephaly and severe psychomotor retardation.	Supravalvular aortic stenosis and other cardiovascular anomalies.
Chromosome 5p deletion confirmed by genetic testing.	Overfriendly personality and strong verbal skills.