Cri du Chat Syndrome

Cri du chat syndrome, also known as Chromosome 5p deletion syndrome, 5p− syndrome, or Lejeune's syndrome, is a rare genetic disorder resulting from a partial deletion of the short arm of chromosome 5.

First described by Jérôme Lejeune in 1963, the syndrome is named after the characteristic cat-like cry of affected infants. The condition occurs in approximately 1 in 50,000 live births and is more prevalent in females by a ratio of 4:3.

Signs and Symptoms

The most distinctive feature of Cri du chat syndrome is the high-pitched, cat-like cry of affected infants, which is caused by abnormalities in the larynx and nervous system. This cry typically diminishes by the age of two. Other significant symptoms include:

• Feeding difficulties due to problems with swallowing and sucking.
• Mutism.
• Low birth weight and poor growth.
• Severe cognitive, speech, and motor disabilities.
• Behavioural problems like hyperactivity, aggression, outbursts, and repetitive movements.
• Unusual facial features that may change over time.

Additional features include excessive drooling, small head (microcephaly) and jaw (micrognathism), widely-spaced eyes (hypertelorism), and skin tags in front of the ears. Common findings also comprise hypotonia, facial features like epicanthal folds, down-slanting eyelids, strabismus, flat nasal bridge, down-turned mouth, and low-set ears.

Cardiac defects such as ventricular septal defect (VSD), atrial septal defect (ASD), patent ductus arteriosus (PDA), and tetralogy of Fallot may also be present. Unlike many genetic disorders, infertility is not associated with Cri du chat.

Genetics

Cri du chat syndrome is primarily caused by a partial deletion of the short arm of chromosome 5, also termed "5p monosomy" or "partial monosomy." Approximately 90% of cases are due to a sporadic, or randomly occurring, de novo deletion. The remaining 10-15% result from unequal segregation of a parental balanced translocation, often accompanied by a trisomic portion of the genome, potentially leading to more severe disease.

Most cases involve the total loss of the distal 10-20% of the material on the short arm of chromosome 5. Fewer than 10% have other rare cytogenetic aberrations such as interstitial deletions, mosaicisms, rings, and de novo translocations. The deleted chromosome is of paternal origin in about 80% of de novo cases. Loss of the region in band 5p15.2 correlates with most clinical features, except for the cat-like cry, which maps to band 5p15.3.

Genes such as Semaphorine F (SEMA5A) and delta catenin (CTNND2) are implicated in cerebral development, while the deletion of the hTERT gene at 5p15.33 may contribute to phenotypic changes.

Diagnosis

Diagnosis is usually based on the distinctive cry and accompanying physical signs, which are readily observable in infants. Genetic counselling and testing are often offered to families with affected individuals. Prenatal detection of the deletion in chromosome 5 can be achieved through amniotic fluid or chorionic villi samples using BACs-on-Beads technology. A G-banded karyotype of a carrier can also be informative.

Treatment

There is no specific treatment for Cri du chat syndrome as the brain damage associated with the condition occurs during early embryonic development. Intensive treatment is rarely required for infants, who are generally managed in neonatal pathology departments.

Speech, physical, and occupational therapies are recommended, especially if infants have difficulties with swallowing or sucking. Cardiac abnormalities may necessitate surgical intervention and specialist care.

Prognosis

The prognosis is generally good once the child has survived the early years of life, with a low mortality rate. In reported cases, the mortality rate is around 10%, with 75% of deaths occurring within the first three months of life and 90% within the first year.

---

Self-assessment MCQs (single best answer)

Which chromosome is affected in Cri du chat syndrome?

What is the characteristic cry of infants with Cri du chat syndrome described as?

Who first described Cri du chat syndrome?

What is the prevalence of Cri du chat syndrome in live births?

Which gene is implicated in cerebral development in Cri du chat syndrome?

Which cardiac defect is NOT commonly associated with Cri du chat syndrome?

Which of the following is NOT a feature of Cri du chat syndrome?

What percentage of Cri du chat syndrome cases are due to a sporadic, or randomly occurring, de novo deletion?

Which of the following is a common behavioural problem in individuals with Cri du chat syndrome?

Which diagnostic method can be used prenatally to detect the deletion in chromosome 5?