Cri Du Chat Syndrome

Synonyms: CdCS, 5p deletion, 5p minus, Cri-du-chat - Lejeune syndrome, Lejeune syndrome, cat cry syndrome.

This is a congenital anomaly caused by partial deletion of the short arm of chromosome 5 (5p-) The affected infant makes a characteristic high-pitched mewing cry like a cat, and associated features include growth failure, other congenital abnormalities and mental retardation.¹ Generally, the greater the loss of chromosomal material, the more severe the clinical picture.²

• The incidence is said to be around 1 in 50,000 infants. There is a slight female preponderance with a ratio of about 4:3.
  It accounts for between 0.15% and 1% of patients with severe learning difficulties.
• Most cases appear to be spontaneous mutations but approximately 15% have a parent with a balanced rearrangement. The abnormal chromosome is paternal in origin in 80% of cases.³
• The risk of recurrence for a de novo case is 1% or less. Rare recurrences when parents have normal chromosomes are most likely the result of gonadal mosaicism in one of the parents.
• If a parent is a balanced carrier of a structural rearrangement, the risk is substantial. Risk should be assessed based on the type of structural rearrangement and its pattern of segregation.

Because of variation in the size of the deletion, there can be considerable variation in the condition.
The following features are typical:^4,5

• There is a high-pitched cry like a cat, giving the syndrome its name. It is due in part to both laryngeal hypoplasia and malfunction within the CNS.⁶ The cry disappears with time and about a third have lost it by the second birthday.
• Low birth weight and slow growth
• Feeding difficulties and failure to suck
• Microcephaly
• Hypertelorism
• Downward slant to the eyes (palpebral fissures)
• Micrognathia
• Low-set ears that may be malformed
• Skin tags just in front of the ear
• Partial webbing or fusing of fingers or toes (syndactyly)
• Simian crease (single palmar crease)
• Mental retardation
• Slow or incomplete development of motor skills

A number of other less distinctive features are also often found.

• Inguinal hernia
• Diastasis recti (separation of rectus abdominis)
• Low muscle tone
• Prominent epicanthal folds
• Incompletely or abnormally folded external ears
• Cardiac abnormalities including ventricular septal defect, atrial septal defect, patent ductus arteriosus and Fallot's tetralogy
• Thymic dysplasia
• Malrotation of the gut

Behavioural problems

A number of abnormalities of behaviour have been described. They may present in variable amounts:

• Hyperactivity
• Aggression
• Tantrums
• Stereotypical behaviour and self-injury
• Repetitive movements
• Hypersensitivity to sound
• Clumsiness
• Obsessive attachments to objects⁷

• Patau's Syndrome - trisomy 13
• Wolf-Hirschhorn Syndrome - partial deletion of chromosome 4⁸

The single palmar crease is seen more often in Down's syndrome.

• Chromosome analysis should show a missing portion of the short arm of chromosome 5. If it does not, a FISH analysis⁹ may reveal that a small piece of this chromosome is missing.
• Lateral x-ray of skull may show an abnormal angle to the base of the skull.

Although the pathognomonic mewing cry usually prompts chromosome analysis, the diagnosis is sometimes delayed. A large study from Italy⁴ found that the diagnosis was made in the first month of life in 42% and within first year in 82% of cases. The remaining 18% were diagnosed at an age ranging from 13 months to 47 years.

• Supportive (both patients and parents) - often the most difficult problem is the child's maladaptive behaviour.¹
• Impaired growth is common in Cri du Chat, which may in part be secondary to feeding problems.¹⁰ Growth and nutrition should be monitored to ensure that growth is not hindered by undernutrition.
  Sometimes a gastrostomy is performed in infancy to protect the airway where there are major feeding difficulties.
• Congenital heart defects may need correction. Minor malformations such as strabismus and clubfoot can be treated surgically. Orchidopexy may be required for undescended testes. Defects of the heart or airways may cause difficulties for the anaesthetist.¹¹

Pneumonia, including aspiration pneumonia, congenital heart defects, and respiratory distress syndrome are the most common causes of death.

Vast majority of cases have good survival expectations, although about 10% of cases die in the first year of life. Disability is quite variable, but some patients are currently living beyond 50 years of age.

Improvements in management (especially rehabilitative programs) have allowed greater psychomotor development, social adaption and improved autonomy.

• Many children develop some language and motor skills.⁴ They attain developmental and social skills of 5 to 6 years old children, but their language is less advanced.¹³
• Older children are usually able to walk, to communicate with words or through gestures and are independent in self-care skills.
• In an Italian study, the oldest patient was 61 years.⁴

Female patients are fertile¹⁴ and can deliver viable offspring, with an estimated risk of recurrence of 50%.

Most cases are spontaneous mutations, so risk of recurrence is extremely low. After an affected child, prenatal diagnosis can be offered for future pregnancies. Where there is a balanced familial translocation the risk of transmission is 8.7-18.8%.^1,15

Jérome Jean Louis Marie Lejeune was a French paediatrician who was born in 1926 and died in 1994. He confirmed the theory of Petrus Waardenburg, from 1932, that Down's syndrome might be the consequence of a chromosomal aberration. He identified the extra chromosome in 1958. Down's was the first chromosomal disorder to be positively identified. He described Cri du Chat syndrome in 1963 although it was later before the chromosomal origin was identified.