Cri du Chat Syndrome

What is Cri du Chat Syndrome?

Cri-du-Chat in French means cat´s cry. This syndrome (also known as 5p- deletion) is a chromosomal disorder, when a piece of chromosome 5 is missing or deleted. Infants born with this disease usually have a high pitched cry, that sound like a cats cry therefore the disease was named Cri du Chat. People affected by this disease can have intellectual and development delay, microcephaly and distinct facial features ^[1].

Symptoms

Usually the first symptom when the baby is born is the characteristic cry. The atypical face and body features together with the characteristic cry prompt further diagnostic evaluation. The cry goes away with time and 1/3 of the patients don´t exhibit the cry by 2 years of age.

The physical features presented at the time of birth are:

• Small chin

• Rounded face
• Skin folds over the eyes, similar to Down´s syndrome
• Ocular hypertelorism- wide-set eyes
• Low set ears, that can be abnormally shaped
• Micrognathia- abnormally small jaw
• Syndactily of fingers and toes- presence of skin webs between the fingers
• A single transverse line on the palm of the hand
• Possible inguinal hernia
• Almost all affected children have severe motor and cognitive development delays ^{[1, 2]}

Neonatal period

The neonatal period refers to time interval from birth until 28^th day of life. Infants in this period can have problems gaining weight, because of difficulties swallowing and sucking. In some cases that can lead to dehydration, pneumonia respiratory distress syndrome and jaundice. Other common findings include:

• Muscle hypotonia
• Low weight at birth
• Strabismus (crossed eyes)
• Short fingers
• Cardiac abnormalities- defects of the ventricular or atrial septum, Fallot tetralogy

Some patients can present with:

• Cleft lip
• Intestinal problems like gut malrotation, megacolon
• Renal malformations- ectopia or agenesis of kidney, hydronephrosis
• Chriptorchidism
• Skeletal and muscular conditions- pes planus, club foot, hip dislocation, clinodactyly (curvature) of 5^th finger, syndactyly (united fingers), hypermobility syndrome ^{[1, 3]}

Childhood

In childhood period the following signs can be observed:

• Mental retardation
• Delay in physical development
• High muscle tone
• Microcephaly
• Small face
• Facial muscles are relaxed therefore an open mouth expression, or dropped jaw can be observed
• Respiratory involvement: often ear and upper respiratory tract infections
• Constipation^[1,3]

Adolescence

In late childhood and adolescence period mental retardation is more pronounced. The facial features become coarse. Scoliosis might be present. The female reproductive system is usually normal. Patients reach puberty and develop secondary sex characteristics and menstruation. For males testes can be small, but reproduction function is usually normal ^[1,3].

Behavioral Symptoms

Children with this syndrome can present with hyperactivity and aggression, which can lead to self injurious behavior. Hypersensitivity to sound is one of the main characteristics of Cri du Chat syndrome, and can cause severe discomfort. Patients can obsessively attach to certain objects, like toys. Delay in motor function can be a cause for injuries and clumsiness. Some patients present with autism-like symptoms and social withdrawal. Still, children affected with this syndrome are able to communicate and interact with others^[1].

Causes

Cri du Chat syndrome is caused by partial deletion of the chromosome 5 or deletion of any lengths from the short arm of chromosome 5. The exact cause for this occurrence is still unknown, but it is believed that deletion occurs in the time of fertilization. This syndrome is not inherited, but in most cases (around 80%) the deletion comes from the father.

Severity of symptoms depends for every patient. Humans have 23 pairs of chromosomes- 22 somatic and 1 pair of sex chromosomes. Each chromosome has a short and a long arm. Chromosomes are further divided in bands that include genes.

That is why symptoms are so variable, depending on the length and location of the deletion. In rare cases this syndrome can be caused by parental translocation (unequal exchange of chromosome material, resulting in loss of genetic material) or cytogenetic aberrations (change in the normal structure of chromosomes).

The characteristic cat-like cry is due to structural abnormality of larynx and dysfunction of the central nervous system. The laryngeal abnormalities can vary in severity for different patients. Larynx might appear normal, but it can also be hypoplastic. Vocal cords might be asymmetric.

Two separate regions of chromosome 5 have been identified:

• Deletion of 5p15.3 region of chromosome 5 results in the typical cry and speech delay
• Deletion of 5p15.2 region of chromosome 5 presents with other clinical features^{[4, 5]}

Diagnosis

Diagnosis of Cri du Chat syndrome is made based on physical examination and laboratory findings. To assess the severity of this syndrome, also imaging studies and some other tests are done. Other syndromes, for example, Velocardiofacial syndrome can present with similar symptoms, therefore it is important to determine the exact chromosomal disruption.

Laboratory findings

• Cytogenic studies determine the severity of chromosome 5 deletion
• In patients with very small deletions, high resolution cytogenic studies or fluorescent in situ hybridization (FISH) studies are used

Imaging studies

• X-ray imaging can determine microcephaly, cranial malformations, like cranial base malformation. Disproportions in the length of fingers and toes can also be properly assessed with X-ray imaging.
• Magnetic resonance imaging can be used to assess different brain structures
• Echocardiography is used to assess heart and possible heart malformations
• Other tests include cognitive function assessment, swallowing function tests, language assessment ^[1,2,3].

Treatment

There is no treatment for Cri du Chat syndrome. Management depends on the severity of symptoms.

Patients with this syndrome often present with upper respiratory tract infections, due to swallowing problems. In patients with severe feeding issues, gastrostomy can be performed. The use of this procedure allows avoiding possible aspirationBehavioral therapy and early language stimulation benefits to the patient’s ability to communicate and socialize. Surgical intervention might be necessary to fix congenital heart defects, clubfoot or strabismus ^[1].

Life Expectancy

The incidence of Cri du Chat syndrome ranges from 1 in 15,000 to 50,000 live births. In some mild cases, this syndrome can be left undiagnosed. There is no racial predilection for this syndrome, but it occurs more often in females.

If the proper measures are taken, patients can survive to adulthood. Mortality rate is 6-8% in overall population. Most common causes of death are due to lung and heart involvement- pneumonia and respiratory distress syndrome, heart defects ^[1,3] .

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References

1. http://emedicine.medscape.com/article/942897-overview
2. http://www.healthline.com/health/cri-du-chat-syndrome#Overview1
3. https://rarediseases.org/rare-diseases/cri-du-chat-syndrome/
4. https://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome#genes
5. https://www.genome.gov/19517558/learning-about-cri-du-chat/