NORD gratefully acknowledges Scott Pentiuk MD, Assistant Professor of Pediatrics, Cincinnati Children's Hospital Medical Center, and Adam Mezoff, MD, Professor of Pediatrics, Cincinnati Children's Hospital Medical Center, for assistance in the preparation of this report.
Cri du chat syndrome (CdCS or 5p-) is a rare genetic disorder in which a variable portion of the short arm of chromosome 5 is missing or deleted (monosomic). Symptoms vary greatly from case to case depending upon the exact size and location of the deleted genetic material. Common symptoms include a distinctive cry that resembles the mewing of a cat, characteristic facial features, slow growth, and microcephaly, a condition that indicates that head circumference is smaller than would be expected for an infant's age and sex. Affected children also exhibit delays in the acquisition of skills requiring the coordination of muscular and mental activities (psychomotor disability) and moderate to severe intellectual disability. Additional symptoms affecting different organ systems of the body can also occur. Most cases are thought arise from spontaneous (de novo) genetic errors very early in embryonic development.
The disorder was first described in the medical literature in 1963 by doctor Lejeune who named the disorder after the distinctive cat-like cry. In French, Cri du chat translates into “cry of the cat”.
The symptoms of cri du chat syndrome vary from case to case. The characteristic high-pitched, shrill cry associated with cri du chat syndrome is present during the first few weeks of life. The cry, which resembles the mewing of a cat, becomes less pronounced as affected infants grow older.
Affected infants may also display low birth weight, growth deficiencies, diminished muscle tone (hypotonia), and microcephaly, a condition that indicates that head circumference is smaller than would be expected for an infant’s age and sex.
Distinctive facial features may include an abnormally round or plump (moon) face, a broad nasal bridge, widely spaced eyes (hypertelorism), crossed eyes (strabismus), downwardly slanting eyelid folds (palpebral fissures), vertical skin folds that may cover the eyes’ inner corners (epicanthal folds), low-set ears, and an abnormally small jaw (micrognathia). Improper alignment of the upper and lower teeth (malocclusion) may also occur.
Additional facial features include an abnormally small distance from the upper lip to the nose (short philtrum), incomplete closure of the roof of the mouth (cleft palate), an abnormal groove or gap in the upper lip (cleft lip), and abnormal fullness of the lower lip. In addition, the fleshy mass (uvula) that hangs in the back of the throat may be spilt (bifid uvula). As affected infants age the face may lose its plumpness and become abnormally long and narrow.
Most affected infants also display some degree of psychomotor and intellectual disability. Psychomotor disability is a delay in the acquisition of skills requiring mental and muscular activities such head control, sitting up, and walking. About half of children with cri du chat syndrome were able to dress themselves by age 5 years. Moderate to severe intellectual disability is present in most cases. Speech development is especially delayed in children with cri du chat syndrome. Affected children usually understand speech better than they can communicate. Some children may display hyperactivity or self-abusive behaviors. While children with cri du chat syndrome are born hypotonic (low muscle tone), they tend to become hypertonic (high muscle tone) as they grow older.
Affected infants may have feeding difficulties due to low muscle tone, poor suck, and gastroesophageal reflux disease. Some are also at risk for aspiration which can lead to pneumonias. In one study, only 50% of children with cri du chat syndrome were able to feed themselves with a spoon by 3.5 years of age.
A variety of additional findings may occur in association with cri du chat syndrome. Abnormal side-to-side curvature of the spine (scoliosis) is a frequent complication. Affected children also have a higher risk of ear infections and hearing loss. Approximately 15-20 percent of affected infants have congenital heart defects. The most common heart defect is patent ductus arteriosus, a condition in which the passage (ductus) between the blood vessel that leads to the lungs (pulmonary artery) and the major artery of the body (aorta) fails to close after birth.
Less common findings associated with cri du chat syndrome include the development of a tear in the supportive tissue of the lower abdomen (inguinal hernia) allowing a portion of the intestines to protrude out; the passage or flowing back (reflux) of the contents of the stomach or small intestines (duodenum) into the esophagus (gastroesophageal reflux); abnormalities of the kidney and urinary tract; respiratory difficulties; webbing of the fingers and toes (syndactyly); abnormal bending or curving of the pinkies inward toward the fourth finger (clinodactyly); clubfeet; and structural anomalies of the voice box (larynx). In some cases, nearsightedness (myopia) and cataracts may develop. Prematurely graying of the hair has also been reported. Some individuals may develop repeated respiratory and intestinal infections. In affected male infants, the testes may fail to descend into the scrotum (cryptorchidism) and the urinary opening may be located on the underside of the penis (hypospadias). There has also been an association with cri du chat and Hirschsprung’s disease.
Cri du chat syndrome is a chromosomal disorder caused by a partial deletion (monosomy) of a varying length of the short arm (p) of chromosome 5. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”.
Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 5p15.3” refers to band 15 on the short arm of chromosome 5. The numbered bands specify the location of the thousands of genes that are present on each chromosome. In individuals with cri du chat syndrome, the range and severity of associated symptoms and findings can vary, depending upon the exact length or location of the deleted portion of chromosome 5p. Researchers have determined that certain symptoms may be associated with specific regions on the short arm of chromosome 5. Researchers have identified several genes that are believed to play a role in the development of cri du chat syndrome. The telomerase reverse transcriptase gene that is located on the short arm of chromosome 5 at band 13.33 (5p13.33) and semaphorin F gene at 5p15.2 could contribute to the wide variety in features. The deletion of the d-catenin gene, also at 5p15.2, is linked to more severe intellectual disability as this protein is expressed in early neuronal development. If researchers can link specific sets of symptoms and findings (phenotypes) to specific deletion of chromosome 5p, it may greatly aid in diagnosis and prognosis.
Most cases of cri du chat syndrome appear to occur spontaneously (de novo) for unknown reasons very early in embryonic development. Most deletions (80-90%) are paternal in origin meaning they likely occur as part of sperm formation. The parents of a child with a “de novo” deletion usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.
In approximately 10-15 percent of cases, cri du chat syndrome may result from a balanced translocation involving chromosome 5p and another chromosome or chromosomes. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. Such translocations may occur spontaneously for unknown reasons (de novo) or be transmitted by a parent who is a carrier of such a balanced translocation. A balanced translocation consists of an altered but balanced set of chromosomes and is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier’s offspring. Chromosomal analysis may determine whether a parent has a balanced translocation.
Cri du chat syndrome affects females more often than males. The incidence ranges from 1-15,000 to 50,000 live births. Some cases of cri du chat syndrome may go undiagnosed making it difficult to determine the true frequency of this disorder in the general population.
In newborns, the diagnosis of cri du chat syndrome is confirmed by a thorough clinical evaluation, identification of characteristic findings (e.g., cat-like cry) and chromosomal studies (karyotyping) that reveal a deletion on the short arm of chromosome 5. A specific test known as fluorescence in situ hybridization (FISH) may be used to confirm a diagnosis of cri du chat syndrome.
Chromosomal studies may also be performed to determine whether a balanced translocation is present in one parent. Additional diagnostic tests may be used to determine the extent of the disorder such as x-rays to reveal skeletal abnormalities such as scoliosis.
Scientific techniques in determining chromosomal abnormalities are becoming more and more refined. This means diagnostic techniques have improved and in certain instances prenatal diagnosis of cri du chat syndrome is possible.
The treatment of cri du chat syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedists, surgeons, cardiologists, speech pathologists, neurologist, dentist, physical and occupational therapists, and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment. As some children with cri du chat can have sensory-neural deafness, auditory testing should be performed.
Early intervention is important in ensuring that children with cri du chat syndrome reach their highest potential. Services that may be beneficial may include special remedial education, physical therapy, speech therapy, special services, and other medical, social, and/or vocational services. Most children are enrolled in therapy before one year of age.
Surgery may be performed to treat a variety of symptoms potentially associated with cri du chat syndrome including congenital heart defects, strabismus, scoliosis, clubfoot, cleft palate and cleft lip.
The survival for children with cri du chat is generally good. Most syndrome related deaths occur within the first year of life. Several children have lived to be over 50 years of age.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Research and studies of cri du chat syndrome are ongoing. One study has shown that early special schooling, a home environment (rather than an institutional one), and family support may help the patient achieve the abilities of a normal five or six year old. In the same study half the children over ten who had undergone special schooling and lived in a supportive home environment, were able to communicate adequately.
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Contact for additional information about cri du chat syndrome:
Scott Pentiuk, MD
Associate Professor of Pediatrics
Cincinnati Children’s Hospital Medical Center
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