CRI-DU-CHAT SYNDROME

Alternate Names: Chromosome 5p deletion syndrome; 5p minus syndrome; Cat cry syndrome

Patients with Cri-du-chat syndrome.

Overview: Cri-du-chat syndrome is an autosomal deletion syndrome caused by partial deletion of the p arm of chromosome 5. The characteristic cry which is perceptually and acoustically similar to a cat’s cry is due to structural abnormality in the larynx and CNS dysfunction. Growth failure, microcephaly, facial abnormalities and mental retardation throughout life is also manifested.

Cri-du-chat syndrome is an autosomal deletion syndrome caused by a partial deletion of chromosome 5p and is characterized by a distinctive, high-pitched, catlike cry in infancy with growth failure, microcephaly, facial abnormalities, andmental retardation throughout life.

Characteristic/Phenotype: A partial deletion of the short arm of chromosome 5 is responsible for the characteristic phenotype.

• Cry that is high-pitched and sounds like a cat
• Downward slant to the eyes
• Low birth weight and slow growth
• Low-set or abnormally shaped ears
• Intellectual disability
• Partial webbing or fusing of fingers or toes
• Single line in the palm of the hand
• Skin tags just in front of the ear
• Slow or incomplete development of motor skills
• Small head (microcephaly)
• Small jaw (micrognathia)
• Wide-set eyes
• Intellectual disability

Frequency: Cri-du-Chat Syndrome affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio.

Diagnosis: Conventional Cytogenetic Studies can detect larger deletions, especially if the entire short arm is missing, while high resolution cytogenetic studies can identify smaller deletions (5p15). Fluorescence in situ hybridization can detect even smaller deletions using genetic markers via the absence of fluorescent signal from either the maternal or paternal chromosome 5p regions.

Chromosome comparative genomic hybridization (CGH) is capable of screening the entire genome for DNA copy-number alterations in a single hybridization. Microarray CGH can detect single-copy aberrations affecting individual clones by using array elements from large-insert genomic clones.

Skeletal radiography can be employed to detect skeletal malformations, MRI for morphological brain abnormalities and echocardiography for structural heart defects.

Causes: It was estimated that most cri-du-chat syndrome cases are the result of de novo deletions (about 80%), some derive from a familial rearrangement (12%), and only a few show other rare cytogenetic aberrations, such as mosaicism (3%), rings (2.4%), and de novo translocations (3%).

Most cases involve deletions of terminal parts of the chromosome with 30-60% loss of 5p material. Approximately 1-2% of cases have recombinations that involve a pericentric inversion in one of the parents.The occurrence of mosaicism is a very rare finding, with frequency estimated at about 3% of patients.  Dicentric chromosome formation with subsequent breakage and telomere healing during meiosis  explains viable terminal deletion after a parental paracentric inversion.

The chromosome 5 with a deleted protion originates from the father in 80% of the cases.

Other Data: The chance of survival to adulthood is possible, using contemporary interventions. The mortality rate of cri-du-chat syndrome is 6-8% usually brought about by pneumonia, aspiration pneumonia, congenital heart defects, and respiratory distress syndrome.

Treatment/Recommendations/Therapies: No treatment is available for cri-du-chat syndrome although caring strategies can be employed.

Genetic counselling is needed to inform parents of the condition and to approximate recurrence risks in families based on possible structural rearrangements of chromosome 5 of either parents. Female patients are usually fertile (with 50 % recurrence risk) may also require counselling.

Patients are predisposed to upper respiratory tract infections, otitis media, and severe constipation, all of which require appropriate treatment.

Special methods harnessing receptive skills must be used rather than traditional verbal methods to facilitate language and communication development. Sign language may also be useful if taught and introduced early into life.

Hyperactivity, short attention span, low threshold for frustration, and self-stimulatory behaviors (eg, head-banging, hand-waving) may be managed with behavior modification programs.

Computerized training for visual-motor coordination is proven to improve the visuo-spatial performance of afflicted children.

Surgery may be required to correct structural malformations (airway tract anomalies,  congenital heart diseases, clubffot, strabismus and others.

Gastrostomy (surgical opening of stomach) must be considered during infancy to protect the airway in patients with major feeding difficulties.

Support Groups:

Five p minus Society

http://www.fivepminus.org/

References:

Genetics Home Reference. (2013). Cri-du-chat Syndrome. Retrieved March 12, 2013 from the URL: http://ghr.nlm.nih.gov/condition/cri-du-chat-syndrome

Haldeman-Englert, C. (2011). Cri-du-chat Syndrome. Retrieved March 12, 2013 from the URL: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002560/

Chen, H. (2011). Cri-du-chat syndrome. Retrieved March 12, 2013 from the URL: http://emedicine.medscape.com/article/942897-overview

Photo from: http://upload.wikimedia.org/wikipedia/commons/thumb/c/c9/Criduchat.jpg/230px-Criduchat.jpg