Cri-du-Chat Syndrome (CdCS), also called 5p- syndrome, is a rare genetic condition affecting an estimated 1 in 15,000 to 50,000 live births. It is a chromosomal disorder named for the characteristic high-pitched cry of affected infants, which often sounds like a kitten’s meow. This unique cry is caused by abnormal development of the larynx and central nervous system. The disorder results from a structural change in a chromosome, leading to a spectrum of developmental and physical challenges.
The Chromosomal Basis of Cri-du-Chat Syndrome
The fundamental biological cause of Cri-du-Chat Syndrome is the loss of genetic material from one copy of chromosome 5. The deletion occurs on the short arm (designated ‘p’), leading to the term “5p deletion” or “5p- syndrome.” Most cases involve a terminal deletion at the end of the short arm, though interstitial deletions within the arm are also possible.
The size of this missing segment varies significantly, typically ranging from 10 to 20% of the short arm’s total length. This loss results in partial monosomy, meaning cells have only one functional copy of the genes in the deleted region instead of two. The severity of the syndrome’s features, such as intellectual disability, often correlates with the size of the deleted segment.
Two separate regions on the short arm of chromosome 5 are involved in the disorder’s features. Region 5p15.3 is associated with the characteristic cat-like cry, and region 5p15.2 is linked to other physical features and intellectual disability. The loss of multiple genes within these critical regions leads to the developmental and physical characteristics of the syndrome.
Distinguishing Between Sporadic and Inherited Forms
The overwhelming majority of Cri-du-Chat Syndrome cases are not inherited but occur spontaneously. Approximately 85% to 90% of cases are de novo, meaning the deletion is a new, random event. This event typically takes place during the formation of reproductive cells (egg or sperm) or in the early stages of fetal development.
In these sporadic cases, the parents have structurally normal chromosomes and no family history of the syndrome. The deletion is a genomic accident that cannot be predicted or prevented. Interestingly, the deleted chromosome in de novo cases is paternal in origin in about 80% of instances.
The remaining 10% to 15% of cases are inherited when a parent carries a specific type of chromosomal rearrangement called a balanced chromosomal translocation. In this condition, pieces of two different chromosomes have swapped places without any loss or gain of genetic material. Because all necessary genetic information is present, the parent is typically healthy and shows no symptoms.
However, the parent’s balanced translocation can become unbalanced when passed down to a child. During the formation of reproductive cells, the rearranged chromosomes may separate unevenly. This leads to a gamete containing a chromosome 5 with a missing segment on the short arm, resulting in an unbalanced translocation and causing Cri-du-Chat Syndrome.
Assessing Recurrence Risk and Genetic Testing
The determination of recurrence risk depends entirely on the distinction between the sporadic and inherited forms. If the child’s Cri-du-Chat Syndrome is confirmed to be a de novo deletion, the risk of recurrence for subsequent pregnancies is extremely low, generally considered negligible.
If a parental balanced translocation is identified as the cause, the recurrence risk is significantly higher and must be calculated by a genetic counselor. The specific risk percentage depends on the chromosomes involved and the precise nature of the parent’s translocation, ranging from 8.7% to nearly 19% for each subsequent pregnancy.
To accurately determine the risk for future children, parental karyotyping is an essential step following a diagnosis. This blood test analyzes the parents’ chromosomes to see if either one carries a balanced translocation involving chromosome 5. Genetic counseling then explains the specific inheritance pattern, the calculated recurrence risk, and available reproductive options.