What is cri du chat syndrome?

Risk Factors

Most cases are spontaneous, meaning there are no known risk factors. Recent reviews have noted, however, that parents who carry translocations involving the 5p region have a risk of producing a child with cri du chat syndrome; this may account for 10 to 15 percent of all cases. A balanced translocation involves no loss of genetic material and no symptoms in the carrier; however, these translocations can become unbalanced when passed on to the next generation. The risk for male and female carriers is similar.

Etiology and Genetics

Identified by Jérôme Lejeune in 1963, cri du chat syndrome is rare; the Genetics Home Reference website of the US National Library of Medicine estimated in 2014 that the syndrome presents in 1 in 20,000 to 1 in 50,000 babies. The condition accounts for approximately 1 percent of all severe cases of intellectual disability. It is slightly more common in females than in males and affects all ethnic groups. It is an autosomal disorder, involving breakage of the short arm of chromosome number 5. Specific points of breakage, and the extent of the deletion, vary from patient to patient. However, the critical region, recently identified as chromosome band 5p15, is missing in all patients with the cri du chat phenotype. It is believed that breakage of chromosome 5 occurs in the process of meiosis, during development of the egg or the sperm, with about 70 to 80 percent of breaks being paternal (sperm) in origin.

A number of specific genes have been identified as deleted in these chromosomes, and the clinical phenotype of the patients appears to be related to the monosomic condition (presence of only one chromosome copy) in this region, rather than the presence of mutated genes as in many genetic disorders. Through correlation of phenotypic changes and breakpoints, two specific bands have been identified within the 5p15 region. The lack of genes within band 5p15.2 appears to account for many of the neurological findings, including intellectual disabilities, while the distinctive cat cry appears to be the result of a deletion in band 5p15.3. Recent work suggests the presence of two critical but discontinuous regions of the chromosome are involved in producing the etiology of the syndrome. Two genes have been mapped to these regions that may be involved in brain development—SEMA5A (Semaphorine F) and CTNND2 (δ-catenin)—and their presence in only one copy may account for much of the mental disability seen. The cri du chat deletion area is also known to contain the gene for telomerase reverse transcriptase
enzyme (also known as TERT, and found at band 5p15.33), which keeps telomeres, the critical ends of chromosomes, long in cells that divide often. The presence of only one copy of the gene may be related to shortened life span of the chromosomes, as well as other control features of cell growth, and therefore the shortened life span that these patients experience.

Symptoms

Symptoms usually include the distinctive cry (which some children lose by age two); difficulty in sucking and swallowing (including breast-feeding); severe delays in motor function, speech, and cognitive function; low birth weight and slow growth; behavioral problems, including aggression, tantrums, hyperactivity; and, in some cases, repetitive motions. Common facial appearance includes microcephaly (small head), hypertelorism, epicanthal folds, low-set ears, and micrognathia (small teeth). Other symptoms may include hypotonia, constipation, short fingers, heart defects (including patent ductus arteriosis, septal defects, and Tetralogy of Fallot), strabismus, down-turned mouth, and a round face. The distinction between symptoms and secondary complications of the syndrome is very unclear.

Screening and Diagnosis

Prenatal screening (cytogenetic and molecular) is useful in some cases, particularly where one child with cri du chat syndrome already exists in the family. On occasion such screening may be warranted by a combination of ultrasound findings. Diagnosis after birth results from a combination of clinical features that, when taken as a whole, create a distinct phenotype. This phenotype, along with the distinctive cry of the infant, leads to a suspicion of cri du chat syndrome. Diagnosis is confirmed on the basis of karyotype analysis of the chromosomes. Occasionally a mild form of the syndrome goes undiagnosed at birth, but the continued abnormal voice of the infant coupled with deficits of psychomotor skills will lead to diagnosis via karyotype analysis.

Treatment and Therapy

There is no treatment available for the underlying genetic disorder. Therapy, therefore, is focused on the individual symptoms. Surgeries may be required to correct heart defects or other structural errors. Some patients require gastrostomy tubes for feeding, due to laryngeal irregularities or other developmental problems. The degree of intellectual disability will dictate the course of therapy needed for daily functionality.

Prevention and Outcomes

There is no known prevention for cri du chat syndrome. Those with a family history of the syndrome should seek genetic counseling before attempting to become pregnant. Outcomes vary, but often intellectual disability is severe enough that the individual is unable to care for himself or herself or to function constructively in society. About half of affected children learn sufficient verbal skills to be able to communicate.

Bibliography

Genetics Home Reference. "Cri-du-chat Syndrome." Genetics Home Reference. NLM, 14 July 2014. Web. 17 July 2014.

Halderman-Englert, Chad, and David Zieve. :"Cri du Chat Syndrome." MedlinePlus. NIH/NLM, 4 Aug. 2011. Web. 17 July 2014.

Kristoffersen, Kristian Emil. "Inflectional Morphology in Cri du Chat Syndrome: A Case Study." Clinical Linguistics & Phonetics 26.2 (2012): 120–134. Print.

Millichap, J. Gordon. Neurological Syndromes: A Clinical guide to Symptoms and Diagnosis. New York: Springer, 2013. Digital file.

Moss, Joanna, et al. "Social Behavior and Characteristics of Autism Spectrum Disorder in Angelman, Cornelia de Lange, and Cri du Chat Syndromes." American Journal on Intellectual & Developmental Disabilities 118.4 (2013): 262–283. Print.

National Human Genome Research Institute. "Learning about Cri du Chat Syndrome." Genome.gov. NIH/NHGRI, 18 Apr. 2013.

Parker, Philip M. Cri-du-chat Syndrome: A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers. San Diego: ICON Group International, 2007.