Introduction

Cri du Chat syndrome is a rare genetic disorder associated with intellectual disabilities and seizures. While the exact incidence of seizures in this group of individuals is not known, it is important to understand the types of occurring seizures and their methods of diagnosis. 

Definition of Cri du Chat syndrome (CdCS)

Cri du Chat syndrome (also known as CdCS, 5p- or Lejeune Syndrome) is an autosomal dominant disorder that occurs due to the deletion or absence of the short arm of chromosome 5. As such, it often appears written as del5p.CdCS is a rare disorder occurring in 1:15,000 to 1:50,000 of live births.¹

This disorder was first described by the French paediatrician Lejeune in 1963, who named it after the distinctive mewling sound that patients made and which resembled a cat’s cry. In fact, the french expression “Cri du Chat” translates into “cry of the cat”.

The main clinical features of CdCS include a high-pitched monochromatic (catlike) cry, seizures, microcephaly, a large nasal bridge, folds of skin covering the inner corner of the eyes (epicanthal folds), micrognathia and severe intellectual disability.²

Brief overview of seizures and their prevalence in individuals with CdCS

Seizures are defined as abnormal, excessive electrical impulses resulting in an excessive neuronal activity whose manifestations can be motor, sensory, psychological and/or autonomic. As such, seizures can present with various symptoms ranging from rapid eye movements, lapses in attention, involuntary movements which affect the whole body (generalised seizures) or part of the body, to loss of bowel and bladder control and even loss of consciousness. Recurrent seizures occurring more than twice in 24 hours are referred to as epileptic seizures.

Although seizures are not frequently observed in CdCS and other disorders affecting Chromosome 5, there have been reporters of generalised clonic-tonic seizures³ as well as infantile spasms⁴ in children with CdCS. An additional study conducted in Brazil observed that 11% of children with CdCS displayed seizures, although the exact types of seizures displayed were not determined.⁵ 

Seizures can occur at any age, from infancy to adulthood and can differ in severity from mild to severe. They can also have a major impact on the quality of life.

Understanding Cri du Chat syndrome

Genetics and cause of CdCS

Chromosomes make up the genetic structure of all individuals. Humans have 46 chromosomes arranged in 22 pairs of somatic (non-sex) chromosomes and one pair of sex chromosomes. Each chromosome has a short arm (p) and a long arm (q).

In CdCS, there is a partial deletion of the short arm (p) of chromosome 5. The exact length or location of this deletion is responsible for the diverse nature of symptoms and findings associated with this syndrome. Most of the genes involved in CdCS are related to brain development and function, the absence of which results in the emergence of neurological symptoms and developmental delays.

The exact cause of CdCS is unknown, with most cases occurring spontaneously during early embryonic development. The majority of these cases have nonetheless been noted as paternal in origin, which implies that they likely occurred due to defects in sperm formation.⁶ Of note, parents with normal chromosomes can give birth to children with CdCS and their likelihood of having another child with CdCS or another chromosomal abnormality is low.

Common characteristics and symptoms of CdCS

Symptoms of CdCS vary widely. Despite this, the characteristic ‘cat cry’ is found in almost all infants with CdCS during the first weeks of life. Approximately one-third of children no longer exhibit this cry by two years of age.

Infants with CdCS can display distinct facial features such as microcephaly, hypertelorism (eyes wide apart), an abnormal round ‘moon’ face, strabismus, epicanthic folds, low set ears, micrognathia and malalignment of the upper and lower teeth. Additionally, these infants may exhibit a cleft lip and palate, a bifid uvula and struggle with low birth weight, growth deficiencies and hypotonia (low muscle tone). As they grow older, their faces lose their plumpness and become narrower, and they gradually become hypertonic (have excessive muscle tone). 

Developmental delays, speech difficulties, and intellectual and psychomotor disabilities are common among CdCS-affected infants. Feeding difficulties can also emerge in these infants due to their lack of muscle tone and poor suck reflex, which places them at risk of aspiration and subsequent pneumonia.

 Health issues that often occur in association with CdCS include congenital heart defects, gastrointestinal defects (such as inguinal hernias), skeletal anomalies (such as webbed or curved finger bones and clubfoot), and genitourinary anomalies (such as undescended testicles and hypospadias).⁶

Seizures in Cri du Chat syndrome

Few studies have been dedicated to understanding seizures and their underlying mechanisms in CdCS. Among these studies, it was discovered that patients with CdCS can exhibit various types of seizures, including:²

• Tonic-clonic seizures: these rare seizures are characterised by convulsions, muscle stiffness and a loss of consciousness
• Atonic seizures: these seizures involve a sudden loss of muscle tone, resulting in sudden falls or drops
• Myoclonic seizures: these seizures are experienced as sudden spasms of muscle groups
• Absence seizures: individuals with these seizures experience brief lapses in attention that often go unnoticed

Although the exact mechanisms underlying the occurrence of seizures in CdCS are unknown, it has been hypothesised that seizures occur due to genetic mutations that impair neuronal development, leading to abnormalities in brain structure and function. 

However, more research is required to identify the exact regions of chromosome 5 that underlie these seizures and other manifestations of the disorder.

Impact of seizures on individuals with Cri Du Chat syndrome

Effects of seizures on cognitive development and daily functioning

Seizures can have a significant impact on individuals with CdCS, affecting all aspects of their lives. As individuals with CdCS already suffer from developmental delays and speech difficulties, seizures can intensify the challenges associated with their integration into society their ability to learn in order to meet up with their peers.

Additionally, seizures can lead to drawbacks in the pursuit of education, affecting their ability to learn and their participation in school.

Seizures associated with sudden drops in consciousness can also result in an increased risk of injury or death due to the unpredictable nature of seizures.

Diagnosis of seizures in Cri du Chat syndrome individuals 

Due to the diverse nature of Cri du Chat syndrome and the various types of seizures that can occur, especially those with milder forms of presentation such as rapid eye movements or lapses in attention, seizures can often go undiagnosed in CdCS-affected individuals for years. 

The diagnosis can be made through a combination of:

• Clinical history: to determine the details of the seizures as well as assess for any prior episodes
• Physical examination: to assess for injuries and to also rule out other possible causes of seizures
• Karyotype analysis: to confirm the diagnosis of CdCS and determine the exact site of deletion on chromosome 5
• Electroencephalogram (EEG): to assess and monitor the electrical activity in the brain and identify possible underlying patterns of disease
• Imaging tests such as magnetic resonance imaging (MRI) or computed tomography scan (CT scan): to assess for any structural abnormalities

Management and treatment

Strategies for seizure management in individuals with CdCS

There is no specific cure for seizures occurring in individuals with CdCS. The management of seizures in individuals with CdCS requires a vast multidisciplinary approach to ensure appropriate treatment is given. This includes the following treatment modalities:

• Anticonvulsant drugs: to either abort seizures or to prevent the emergence of future seizures
• Psychotherapy: to help individuals cope with the impact of seizures on their life and also address any psychological issues that may arise from the seizures and/or the syndrome itself
• Caregiver seizure first-aid training: to reduce the risk of harm and to treat any injuries that the affected individual may sustain before help can be sought at a treatment facility
• Lifestyle changes, such as identifying and avoiding triggers that can result in the emergence of seizures: to reduce the frequency and severity of the seizures
• Treatment of concurrent symptoms

FAQs

What are the neurological symptoms of Cri du Chat Syndrome (CdCS)?

In addition to seizures, CdCS is also associated with intellectual disabilities, learning and speech difficulties, mental retardation and developmental delays.

What is the most prominent characteristic of individuals afflicted with Cri du Chat Syndrome (CdCS)?

The most distinctive feature common to almost all individuals with CdCS is their mewling, cat-like cry.

Is there a cure for Cri du Chat Syndrome (CdCS)?

There is no cure or specific treatment for CdCS.

Summary

Cri du Chat syndrome (CdCS) is a chromosomal disorder that arises due to a deletion in the short arm of chromosome 5. This syndrome encompasses a wide spectrum of symptoms, including a characteristic cat-like cry, dysmorphic facial features, defects in various organ systems and neurobiological conditions such as seizures.

The presentation of seizures in CdSC can vary from one individual to another and feature tonic-clonic, myoclonic or absence seizures. The exact mechanisms responsible for the emergence of these seizures are unclear but believed to be related to mutations that occur in genes responsible for neurodevelopment.

Research needs to be conducted to determine the exact mechanisms responsible for the emergence of symptoms in this disorder. This will allow its diagnosis to be made earlier and treatment to be instituted sooner, thereby improving the quality of life of these individuals. 

It is also important to provide affected individuals with the support required to cope with the syndrome and seizures through medication, lifestyle changes and psychotherapy.