What is cri du chat syndrome?

Cri Du Chat syndrome is a genetic disorder that is caused by a deletion of a portion of chromosome 5. The name ‘Cri Du Chat’ means ‘the cry of the cat’ which is the most distinct clinical feature typically observed within the first year of life a high-pitched cry that mimics a meowing cat.¹ 

Other characterising clinical features include distinct facial dysmorphism, microcephaly (small head size) and severe delayed development and intellectual disabilities.² An intellectual disability is a neurodevelopmental disorder characterised by a significant limitation in learning abilities, intelligence and everyday activities.

Cri Du Chat Syndrome is considered a rare disorder with an incident rate of 1:15,000 to 1:50,000 live births, interestingly it is one of the most common chromosomal mutations observed in humans. Its incidence was found to be slightly higher in females than males. 

Cri Du Chat Syndrome, commonly denoted as CdCS is also known as 5P syndrome, 5p minus syndrome, cat’s cry syndrome and Lejeune syndrome, named after Professor Lejeune who identified it.

Clinical features of cri du chat syndrome

The most distinct clinical feature observed during the neonatal period is a high-pitched monotonous crying that mimics the sound of a meowing cat. The disease severity and progression is directly dependent on the section of the chromosome missing² and therefore a range of clinical features are observed. These include: 

• Microcephaly (smaller than average head size)
• Large nasal bridge
• Down-turned corners of the mouth
• Hypotonia (low muscle one)
• Growth delay
• High-pitched, monotonous cat-like cry
• Low birth weight
• Feeding difficulties
• Scoliosis (curved spine)
• Webbed toes and fingers (syndactyl) 
• Respiratory difficulties
• Delayed motor skill development
• Delayed speech development
• Mild to severe intellectual disability 

What causes cri du chat?

Cri du Chat Syndrome is classified as a chromosomal disorder caused by a (partial or complete) deletion of the short arm (p arm) of chromosome 5. Chromosomes store genetic information in the form of DNA (deoxyribonucleic acid) in the cell’s nucleus. DNA is tightly packaged within chromosomes, which have two long arms (q arms) And two short arms (p arms).

How is cri du chat diagnosed?

Diagnoses are primarily based on assessment at birth. Distinct symptoms characteristic of Cri Du Chat such as the distinct cat-like cry and abnormal facial features are typically indicative that a newborn has the syndrome. To confirm the suspected disorder, molecular analysis of the chromosomes is done to determine whether the short arm of chromosome 5 is intact. Further genetic testing, known as FISH analysis, may require confirming the diagnosis.

What is an intellectual disability?

Intellectual disabilities (ID) are a lifelong condition that present during childhood and significantly impair cognitive and adaptive function.

Cognitive function includes learning abilities, reasoning, judgement and problem-solving.

Adaptive function- daily activities such as socialising, communication skills and overall ability to live independently.

Intellectual disabilities can be of varying degrees where the range of disease severity can be classified as mild, moderate, severe or profound.³

Mild intellectual disability

Mild ID is the most common classification ID diagnosed. These individuals are slower in conceptual development and day-to-day skills. They require minimal support and can lead an ordinary life.

Moderate intellectual disability

Individuals with moderate ID require moderate support in their care, however, they can learn basic health and safety skills, communicate with simple language and live independently to some extent. 

Severe intellectual disability

Persons living severe ID have major developmental delays and with limited communication skills and understanding abilities. They can learn simple daily routine activities but require support with their day-to-day care.

Profound intellectual disability

Profound ID is categorized as individuals with a significant deficit in their communicative ability and physical abilities. They are unable to lead an independent life and require 24/7 support and care.

Assessing intellectual disabilities

Genetic factors contribute to ID, and these can be determined through genetic testing. In recent years, whole exome sequencing and whole genome sequencing have proven to be reliable diagnostic tools for ID.

ID is typically assessed through IQ testing defined by an IQ score of 70 and by significant limitations in cognitive and adaptive skills. There are two classification systems used to assess ID these are the American Association on Intellectual and Developmental Disabilities (AAIDD and the Diagnostic and Statistical Manual of Mental Disorders, 5^th Edition (DSM-5). DSM-5 diagnosis is based on 3 criteria- limitations in intellectual function, and adaptive function with an onset before 22 years of age (4).

Intervention and support strategies

There is no official treatment for Cri du Chat syndrome. Treatment options are determined on a case-by-case basis. It is crucial to manage intellectual disabilities as early as possible with the main goal of preventing progress and improving the quality of life. During the neonatal period, it is recommended to commence physical therapy as soon as possible to aid in swallowing and suction, and psychomotricity and speech therapy to remedy psychomotor and speech developmental delay.² 

Managing intellectual disability is initiated by healthcare providers and it entails a multidisciplinary approach to minimise the progression of ID. The following interventions are examples of strategies employed to manage intellectual disability. 

Educational support

It is crucial to set up tailored education plans and support in schools to facilitate learning and develop communication and social skills as soon as possible following a diagnosis. These overall aims are to teach communication skills, behavioural skills, and basic functional skills.

Behavioural interventions

Behavioural therapy seeks to reinforce positive behaviours over negative behaviours by practising positive reinforcements. Cognitive therapy is another method of behavioural training which, on its own or in combination with behavioural therapy, has been shown to be effective strategies.

Vocational training

Support is given to teenagers and young people to teach them the required skills to be functional members of the workforce. 

Family education

Family education is available from healthcare providers to assist families in understanding intellectual disabilities and how to support and care for their loved one living with ID. Additional resources are also available for family members who are carers.

Maintaining a healthy diet and routine are also complementary to treatment options. 

Genetic counselling is strongly recommended for any additional pregnancies.

Summary

Cri Du Chat is a genetic disorder caused by a loss of chromosome 5 and the severity depends on the extent of the chromosome deletion. The syndrome is more common in females and occurs in approximately 1 in 15,000 to 50,000 births.

It is also known as 5p syndrome or Lejeune syndrome, and it’s named after the distinct high-pitched cry which is the main clinical feature in newborns with the condition. Other key features include facial dysmorphism, microcephaly (small head size), severe developmental delays and intellectual disabilities.  

Diagnosis is based on the characteristic cry and physical features at birth, confirmed through genetic testing such as FISH analysis.

Intervention strategies focus on a multidisciplinary approach to manage symptoms as early as possible. Treatment plans are dependent on disease severity, and they include a combination of different therapies to improve quality of life.