Cri-du-Chat syndrome: History, Causes, Symptoms, Characteristics, Diagnosis and Treatment

It is a rare congenital disease with a chromosomal alteration.

History

The Cri-du-Chat syndrome was first identified in 1963.

A series of three patients were described with a syndrome consisting of multiple congenital anomalies, mental retardation, microcephaly, abnormal face, and an acute, monotonous, and feline Crying during the first years of a baby’s life (providing the name of the syndrome).

In addition to the typical facial dysmorphisms, intellectual deterioration, and developmental delay, patients presented a deletion of a group B chromosome (Bp-), later identified as 5p.

The 5p deletions causing this syndrome have an incidence of 1 in 50,000 live births and can be terminal (78%), interstitial (9%), or caused by unbalanced translocations (5%) in about 80 percent of cases.

A critical region located between 5p15.2 and 5p15.3 that is responsible for the 5p deletion phenotype was defined by Niebuhr.

It has been reported that the removal of 5p15.2 is responsible for the observed dysmorphism and intellectual disability in these patients, and the proximal region of 5p15.3 has been associated with “feline” crying and speech delay.

 

Molecular studies have confirmed the importance of these regions for pathognomonic signs and have allowed the refinement of specific genes that individually affect the different components of the classical phenotype.

Wu et al . analyzed candidate genes for feline Crying in the Cri-du-Chat critical region through quantitative PCR. We studied the distal cut-off points of two interstitial deletions in two clinically distinct patients with Cri-du-Chat; one patient exhibited feline wail, and the other did not.

The results revealed a candidate gene, FLJ25076 / UBC-E2, mapping between the cut-off points spanning 5p15.3-5p15.2. This segment has a length of 640 kb and encodes an E2-type enzyme conjugated with ubiquitin expressed in the thoracic and scalp tissues.

Other genes that have been assigned to the Cri-du-Chat critical region include the semaphorin F gene (SEMA), which encompasses at least 10% of the deleted chromosomal region, and the delta-catenin (CTNND2) gene, which encodes specific neuronal proteins potentially involved in the brain development.

These genes are associated with intellectual disability. It has been found that the delta-catenin gene regulates the morphogenesis of the spine and synapse and works in hippocampal neurons during development, and may contribute to functional alterations in neural circuits.

In the present investigation, we applied array-CGH (comparative genomic hybridization array) to analyze a small but very heterogeneous group of six patients with Cri-du-Chat diagnosed with conventional cytogenetic techniques.

This study raises new questions regarding the phenotype-genotype correlations of this syndrome. A review of the functions of the genes/loci located in the 5p region is presented.

Cri-du-Chat syndrome is an autosomal deletion syndrome caused by a partial deletion of chromosome 5p. It is characterized by a distinctive cry of sharp tone in childhood with growth failure, microcephaly, facial abnormalities, and mental retardation throughout life.

In recent years, molecular genetic methods introduced advances in the diagnosis and typing of the Cri-du-Chat syndrome.

Cri-du-Chat syndrome, also called 5p syndrome or Lejeune syndrome is a congenital disorder caused by partial deletion of the short arm of chromosome 5.

It is named for its characteristic symptom, a sharp cry that resembles that of a cat (the name in French is ” cat’s cry “), which occurs in most affected babies.

It has an incidence of approximately 1 in every 15,000 to 50,000 live births and occurs in all ethnic groups. It was first described by the French geneticist Jérôme-Jean-Louis-Marie Lejeune and his colleagues in 1963.

Cat crying, which usually decreases with age, is accompanied, to varying degrees, by symptoms of intellectual disability, mild facial anomalies, and abnormal skin patterns (fingerprints and palm prints).

Also, malformations of the heart, a small head (microencephaly), an excessive space between the eyes (ocular hypertelorism), and a failure to thrive.

The severity of the symptoms seems to be related to the size of the chromosomal deletion, and larger deletions are associated with more severe symptoms and a more significant delay in development.

What is Cri-du-Chat syndrome?

Cri-du-Chat syndrome is a genetic condition. It is also called cat syndrome or 5P- syndrome (5P less); it is a deletion in the short arm of chromosome 5.

According to the Genetics reference, it is a rare condition, occurring in approximately 1 in 20,000 to 1 in 50,000 newborns. But it is one of the most common syndromes caused by chromosomal elimination.

“Cri-du-Chat” means “crying cat” in French. Babies with the syndrome produce a sharp cry that sounds like a cat. The larynx develops abnormally due to chromosomal elimination, which affects the sound of the child’s Crying.

The syndrome is more noticeable as the child ages, but it becomes difficult to diagnose after two years.

Cri-du-Chat also entails many disabilities and anomalies.

A small percentage of babies with Cri-du-Chat syndrome are born with severe organ defects (especially heart or kidney defects) or other life-threatening complications that can cause death.

Most fatal complications occur before the child’s first birthday.

Children with Cri-du-Chat who reach the age of 1, in general, will have an average life expectancy. But the child likely has physical or developmental complications for life. These complications will depend on the severity of the syndrome.

Approximately half of the children with Cri-du-Chat syndrome learn enough words to communicate, and most grow up to be happy, friendly, and pleasant.

What causes Cri-du-Chat syndrome?

The exact reason for the elimination of chromosome 5 is unknown. In most cases, the chromosomal break occurs while the sperm or the parent’s egg is still developing. This means that the child develops the syndrome when fertilization occurs.

In most cases, the abnormality occurs spontaneously, with no family history.

The risk that a couple with normal chromosomes have another child with Cri-du-Chat is about one percent. In some cases, one of the parents has abnormalities of chromosome 5.

Genetic counseling for these couples is essential since later children may also have Cri-du-Chat syndrome.

Medical techniques such as amniocentesis, where a sample of amniotic fluid is examined, can determine whether or not an unborn baby has Cri-du-Chat syndrome. Amniocentesis is usually done in the first trimester of pregnancy.

Chromosomal elimination comes from the father’s sperm in approximately 80 percent of cases. However, the syndrome is not typically hereditary.

According to the National Human Genome Research Institute, only about 10 percent of cases come from a father who has a segment removed.

It is presumed that about 90 percent are random mutations.

You may have a type of defect called a balanced translocation. This is a defect in the chromosome that does not result in the loss of genetic material. However, if you pass the defective chromosome to your child, you may become unbalanced.

This results in the loss of genetic material and can cause Cri-du-Chat syndrome.

Your unborn child has a slightly higher risk of being born with this condition if you have a family history of Cri-du-Chat syndrome.

What are the symptoms?

The severity of your child’s symptoms depends on the amount of genetic information missing on chromosome 5. Some symptoms are severe, while others are so small that they can go undiagnosed.

Like a cat, which is the most common symptom, Crying becomes less noticeable over time.

Children with Cri-du-Chat syndrome usually have some motor delay, especially when walking. Some children walk as early as two years, but others may take up to six years due to their low muscle tone. Some may never walk.

Children with Cri-du-Chat syndrome may have a mild to profound intellectual disability. This can range from a slight delay in a speech to a profound intellectual disability.

Some children may never speak. Children with Cri-du-Chat are generally better at understanding what people say than talking.

Physical characteristics

Children born with Cri-du-Chat are often small at birth. They may also experience breathing difficulties. In addition to the namesake cat cry, other physical characteristics include:

  • Small chin
  • Unusually round
  • Bridge of the small nose.
  • Folds of skin over the eyes.
  • Abnormally wide eyes (ocular or orbital hypertelorism).
  • Abnormally shaped or poorly seated ears.
  • A small jaw (micrognathia).
  • Partial tissue of the fingers or toes.
  • A single line in the palm.
  • An inguinal hernia (a protrusion of organs through a weak area or tear in the abdominal wall).

Health problems in children with Cri-du-Chat syndrome

Children with Cri-du-Chat syndrome commonly experience health problems that include:

  • Difficulties with suction and swallowing
  • Gastric reflux
  • Constipation
  • High rate of infections, such as infections of the ear and upper respiratory tract
  • Eye problems, such as strabismus ( strabismus ).

Other complications:

Internal problems are common in children with the condition. Examples include:

  • Skeletal problems such as scoliosis (abnormal curvature of the spine).
  • Defects of the heart or other organs.
  • Hernias.
  • Heart and kidney problems.
  • Poor muscle tone (during childhood and adolescence).
  • Difficulties of hearing and vision.

As they grow up, they often experience problems speaking, walking, and feeding and may have behavioral issues, such as hyperactivity or aggression.

Children can also suffer from severe intellectual disabilities, but they should have an average life expectancy if they do not experience defects with vital organs or other critical medical conditions.

How is the Cri-du-Chat syndrome diagnosed?

Cri-du-Chat syndrome is diagnosed in infants and young children based on clinical symptoms and can be confirmed through chromosomal analysis.

It can be detected before birth through prenatal genetic tests in placental or fetal tissue samples collected by chorionic villus sampling or amniocentesis, respectively.

Language therapy, physiotherapy, and educational intervention can help improve the quality of life of affected people.

The minority of cases of Cri-du-Chat is inherited; the father who carries the genetic anomaly is generally not affected by the disorder due to a phenomenon known as balanced translocation (chromosomal rearrangement in which there is no net gain or loss of genetic material).

The rest of the cases are caused by random chromosomal deletion during fetal development or the generation of ovules and sperm.

The condition is usually diagnosed at birth, based on physical abnormalities and other signs such as typical Crying. Your doctor may perform an x-ray on your child’s head to look for abnormalities at the skull base.

A chromosome test that uses a unique FISH analysis technique helps detect small eliminations.

If you have a family history of Cri-du-Chat, your doctor may suggest a chromosomal analysis or genetic testing while your child is still in the womb.

Your doctor can analyze a small sample of tissue from outside the sac where your child develops (known as chorionic villus sampling) or explore a sample of amniotic fluid.

The severity of the syndrome

The severity of the condition may vary. Some children are only mildly affected and reach developmental milestones, such as walking and talking, at the usual ages. However, they may still need speech therapy.

Other children are profoundly intellectually disabled, unable to walk or talk, and suffer from related health problems and reduced life.

The majority of children born with Cri-du-Chat syndrome are between these two extremes.

They have a moderate intellectual disability, with varying degrees of speech delay and some health problems, but most walk a time before the age of six. It is impossible to predict whether a newborn baby with Cri-du-Chat syndrome will be affected mildly, moderately, or severely.

This will only become clearer as the child grows.

How is the Cri-du-Chat syndrome treated?

There is no specific treatment for Cri-du-Chat syndrome. It can help control symptoms with physical therapy, language and motor skills therapy, and educational intervention.

Cri-du-Chat syndrome (CDC), caused by a deletion involving the short arm of chromosome 5, is observed in 1: 15,000 to 1: 50,000 newborns.

The “Nguyen et al. Respond “reported a comprehensive review of clinical and molecular data, suggesting life expectancy may be average without significant malformations.

For the general population, the relationship between aging and cancer development is well known.

As the number of Cri-du-Chat patients who survive into adulthood increases, it is interesting to know whether the genetic background, including removing the short arm of chromosome 5, plays an additional role.

These data for patients with Cri-du-Chat are entirely non-existent.

There is no cure for the cri-du-Chat syndrome. The goal of treatment is to stimulate the child and help him reach his maximum potential and may include:

  • Physiotherapy to improve poor muscle tone.
  • Speech therapy.
  • Alternative communication, such as sign language, since speech is often delayed, often severely.
  • Occupational therapy teaches coping strategies and new skills.

Support services for parents of children with disabilities include:

  • Advice.
  • Information.
  • Remission.
  • Advocacy.
  • Support groups.

How can a Physiotherapist help?

A pediatric physiotherapist can help your child develop strength and progress through his milestones in gross motor skills from infancy to childhood, from rolling to walking, running, or jumping.

Assessing your child at regular intervals will also help to establish realistic gross motor goals and help to analyze the prognosis in terms of motor development since each child with Cri-du-Chat syndrome is different.

A physiotherapist can also identify sports and community-based activities to help with the inclusion and development of gross motor skills, such as tricycle, hydrotherapy, and horse riding.

They can also monitor your child’s musculoskeletal system as they grow up, looking for signs of scoliosis and flat feet, and promptly refer consultants, orthopedists, and other therapists to improve their child’s development and health.

What to do when a child has been diagnosed with Cri du Chat Syndrome?

After diagnosis, parents will see a genetic counselor. Depending on the counselor’s experience, they may or may not give accurate information.

Just remember, each child will have their timeline. It will be difficult not to compare the child with Cri-du-Chat syndrome with other “normal” children of his age. Children with Cri-du-Chat syndrome can do much more than what they will be told. . . . at your own pace.

In a short time, the parents become experts in the syndrome. They will know more about the syndrome than doctors, therapists, or teachers. They become great educators!

Parents will soon learn terms they did not even know existed, becoming advocates and their children’s voices. Parents should consider early intervention, speech therapy, physiotherapy, and occupational therapy.

Sign language and other forms of communication through devices should be introduced at the beginning of the child’s life. A child with Cri-du-Chat Syndrome will learn and retain more than they can express.

Because of this, a child will feel frustrated and may develop undesirable behavior problems. Parents, therapists, and educators must work together in the general education of the child and create sustainable goals.

The achievement of goals and simple milestones must be celebrated! Concentrate more on what the child can do and not so much on what he is told he can not or will not do!

Parents must connect successfully through the global support organizations for Cri-du-Chat Syndrome to get a sense of relief and realize that they are not alone in their journey.

By developing links with other families of people with the syndrome, parents discover a wide variation in capacity levels for people with Cri-du-Chat syndrome of all ages.

Families can access strategies that have worked with other children with the syndrome.

Parents are encouraged to use a total communication approach and encourage their children, who tend to be complacent, to work. Knowing the different skills among children can encourage families to participate in intensive early educational training.

Things to remember about the Cri-du-Chat syndrome

Cri-du-Chat syndrome is a rare genetic disorder caused by missing pieces in a particular chromosome. It is not the result of parents’ actions or failure to do.

A newborn baby with Cri-du-Chat syndrome includes a sharp cry, a small head, and a flattened bridge of the nose. The goal of treatment is to help the child reach their full potential.