Cri-du-chat Syndrome 

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 11, 2011
 

Background

  • In 1963, Lejeune et al described a syndrome consisting of multiple congenital anomalies, mental retardation, microcephaly, abnormal face, and a mewing cry in infants with a deletion of a B group chromosome (Bp-), later identified as 5p-.[1]
  • 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, and mental retardation throughout life. See the images below. Infant with cri-du-chat syndrome. Note the round fInfant with cri-du-chat syndrome. Note the round face with full cheeks, hypertelorism, epicanthal folds, and apparently low-set ears. Child with cri-du-chat syndrome. Note the hypertonChild with cri-du-chat syndrome. Note the hypertonicity, small and narrow face, dropped jaw, and open-mouth expression secondary to facial laxity.
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Pathophysiology

  • A partial deletion of the short arm of chromosome 5 is responsible for the characteristic phenotype.
  • The characteristic cry is perceptually and acoustically similar to the mewing of kittens. This unusual cry is due to structural abnormalities of the larynx (eg, laryngeal hypoplasia) and CNS dysfunction. The laryngeal appearance may be normal or may exhibit marked anatomical abnormalities such as floppy epiglottis, small larynx, and asymmetric vocal cords. However, the cause of the characteristic cry cannot be entirely ascribed to the larynx. A developmental field may connect the brain and the affected clivus region of the cranial base with the laryngeal region from which the characteristic cry derives. This area of the brain is probably deformed in patients with cri-du-chat syndrome. The characteristic cry usually disappears over time.
  • Genotype-phenotype studies in cri-du-chat syndrome led to the identification of two separate chromosomal regions, hemizygosity for which is associated with specific phenotypes.[2]
  • A deletion of 5p15.3 results in the manifestation of a catlike cry,[3] whereas a deletion of 5p15.2 results in the presentation of the other major clinical features of the syndrome.[4]
  • Moreover, a region for speech delay in 5p15.3 has been identified.[5]
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Epidemiology

Frequency

United States

  • The estimated prevalence is about 1 in 50,000 live births.
  • The prevalence among individuals with mental retardation is about 1.5 in 1000.

Mortality/Morbidity

  • With contemporary interventions, the chance of survival to adulthood is possible.
  • Currently, the mortality rate of cri-du-chat syndrome is 6-8% in the overall population.
  • Pneumonia, aspiration pneumonia, congenital heart defects, and respiratory distress syndrome are the most common causes of death.

Race

  • No racial predilection has been found.

Sex

  • A significant female predominance is observed in affected newborns, with a male-to-female ratio of 0.72:1.

Age

  • The condition is detected in newborns and infants because of the catlike cry and dysmorphic features.
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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG  Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Ian Krantz, MD  Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia

Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. LeJeune J. [Role of cytogenetics in the study of neoplastic processes]. Rev Prat. Dec 9 1963;13:SUPPL 21-3. [Medline].

  2. Overhauser J, Huang X, Gersh M, et al. Molecular and phenotypic mapping of the short arm of chromosome 5: sublocalization of the critical region for the cri-du-chat syndrome. Hum Mol Genet. Feb 1994;3(2):247-52. [Medline].

  3. Gersh M, Goodart SA, Pasztor LM, et al. Evidence for a distinct region causing a cat-like cry in patients with 5p deletions. Am J Hum Genet. Jun 1995;56(6):1404-10. [Medline].

  4. Goodart SA, Simmons AD, Grady D, et al. A yeast artificial chromosome contig of the critical region for cri-du-chat syndrome. Genomics. Nov 1 1994;24(1):63-8. [Medline].

  5. Church DM, Bengtsson U, Nielsen KV, Wasmuth JJ, Niebuhr E. Molecular definition of deletions of different segments of distal 5p that result in distinct phenotypic features. Am J Hum Genet. May 1995;56(5):1162-72. [Medline].

  6. Cornish KM, Cross G, Green A, Willatt L, Bradshaw JM. A neuropsychological-genetic profile of atypical cri du chat syndrome: implications for prognosis. J Med Genet. Jul 1999;36(7):567-70. [Medline]. [Full Text].

  7. Swanepoel D. Auditory pathology in cri-du-chat (5p-) syndrome: phenotypic evidence for auditory neuropathy. Clin Genet. Oct 2007;72(4):369-73. [Medline].

  8. Niebuhr E. The Cri du Chat syndrome: epidemiology, cytogenetics, and clinical features. Hum Genet. Nov 16 1978;44(3):227-75. [Medline].

  9. Robinson WP, Dutly F, Nicholls RD, et al. The mechanisms involved in formation of deletions and duplications of 15q11-q13. J Med Genet. Feb 1998;35(2):130-6. [Medline].

  10. Perfumo C, Cerruti Mainardi P, Cali A, et al. The first three mosaic cri du chat syndrome patients with two rearranged cell lines. J Med Genet. Dec 2000;37(12):967-72. [Medline].

  11. Ye Y, Luo Y, Qian Y, Xu C, Jin F. Cri du chat syndrome after preimplantation genetic diagnosis for reciprocal translocation. Fertil Steril. Jul 2011;96(1):e71-5. [Medline].

  12. Pizzamiglio MR, Nasti M, Piccardi L, Vitturini C, Morelli D, Guariglia C. Visual-motor coordination computerized training improves the visuo-spatial performance in a child affected by Cri-du-Chat syndrome. Int J Rehabil Res. Jun 2008;31(2):151-4. [Medline].

  13. Mainardi PC, Call A, Guala A, et al. Phenotype-genotype correlation in 7 patients with 5p/autosome translocations. Risk for carriers of translocations involving 5p. Am J Hum Genet. 2000;A753:145.

  14. Torun D, Bahce M, Alanbay I, Guran S, Baser I. Prenatal diagnosis of Cri-du chat syndrome following high maternal serum human chorionic gonodotrophin and choroid plexus cysts. Prenat Diagn. Feb 10 2009;[Medline].

  15. Overhauser J, McMahon J, Oberlender S, et al. Parental origin of chromosome 5 deletions in the cri-du-chat syndrome. Am J Med Genet. Sep 1990;37(1):83-6. [Medline].

  16. Brislin RP, Stayer SA, Schwartz RE. Anaesthetic considerations for the patient with cri du chat syndrome. Paediatr Anaesth. 1995;5(2):139-41. [Medline].

  17. Cerruti Mainardi P. Cri du Chat syndrome. Orphanet J Rare Dis. Sep 5 2006;1:33. [Medline]. [Full Text].

  18. Chen CC, Lee CC, Chang TY, Town DD, Wang W. Prenatal diagnosis of mosaic distal 5p deletion and review of the literature. Prenat Diagn. Jan 2004;24(1):50-7. [Medline].

  19. Chen H. Cri-du-chat syndrome. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Humana Press; 2006:256-260.

  20. Cordier AG, Braidy C, Levaillant JM, et al. Correlation between ultrasound and pathological examination in a prenatal diagnosis of Cri du Chat syndrome associated with partial trisomy 17q. Prenat Diagn. May 2008;28(5):463-5. [Medline].

  21. Cornish KM, Munir F. Receptive and expressive language skills in children with cri-du-chat syndrome. J Commun Disord. Jan-Feb 1998;31(1):73-80; quiz 80-1. [Medline].

  22. Cornish KM, Pigram J. Developmental and behavioural characteristics of cri du chat syndrome. Arch Dis Child. Nov 1996;75(5):448-50. [Medline].

  23. Dykens EM, Clarke DJ. Correlates of maladaptive behavior in individuals with 5p- (cri du chat) syndrome. Dev Med Child Neurol. Nov 1997;39(11):752-6. [Medline].

  24. Fang JS, Lee KF, Huang CT, et al. Cytogenetic and molecular characterization of a three-generation family with chromosome 5p terminal deletion. Clin Genet. Jun 2008;73(6):585-90. [Medline].

  25. Fenger K, Niebuhr E. Measurements on hand radiographs from 32 cri-du-chat probands. Radiology. Oct 1978;129(1):137-41. [Medline].

  26. Gersh M, Grady D, Rojas K, et al. Development of diagnostic tools for the analysis of 5p deletions using interphase FISH. Cytogenet Cell Genet. 1997;77(3-4):246-51. [Medline].

  27. Hills C, Moller JH, Finkelstein M, Lohr J, Schimmenti L. Cri du chat syndrome and congenital heart disease: a review of previously reported cases and presentation of an additional 21 cases from the Pediatric Cardiac Care Consortium. Pediatrics. May 2006;117(5):e924-7. [Medline].

  28. Hodapp RM, Wijma CA, Masino LL. Families of children with 5p- (cri du chat) syndrome: familial stress and sibling reactions. Dev Med Child Neurol. Nov 1997;39(11):757-61. [Medline].

  29. Kjaer I, Niebuhr E. Studies of the cranial base in 23 patients with cri-du-chat syndrome suggest a cranial developmental field involved in the condition. Am J Med Genet. Jan 1 1999;82(1):6-14. [Medline].

  30. Kondoh T, Shimokawa O, Harada N, et al. Genotype-phenotype correlation of 5p-syndrome: pitfall of diagnosis. J Hum Genet. 2005;50(1):26-9. [Medline].

  31. Mainardi PC, Perfumo C, Cali A, et al. Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation. J Med Genet. Mar 2001;38(3):151-8. [Medline]. [Full Text].

  32. Manning KP. The larynx in the cri du chat syndrome. J Laryngol Otol. Oct 1977;91(10):887-92. [Medline].

  33. Martinez JE, Tuck-Muller CM, Superneau D, Wertelecki W. Fertility and the cri du chat syndrome. Clin Genet. Apr 1993;43(4):212-4. [Medline].

  34. Moreira LM, de Carvalho AF, Borja AL, et al. Mosaic cri-du-chat syndrome in a girl with a mild phenotype. J Appl Genet. 2008;49(4):415-20. [Medline].

  35. Mosca AL, Callier P, Leheup B, et al. Fortuitous FISH diagnosis of an interstitial microdeletion (5)(q31.1q31.2) in a girl suspected to present a cri-du-chat syndrome. Am J Med Genet A. Jun 15 2007;143A(12):1342-7. [Medline].

  36. Moss JF, Oliver C, Berg K, Kaur G, Jephcott L, Cornish K. Prevalence of autism spectrum phenomenology in Cornelia de Lange and Cri du Chat syndromes. Am J Ment Retard. Jul 2008;113(4):278-91. [Medline].

  37. Niebuhr E. The cat cry syndrome (5p-) in adolescents and adults. J Ment Defic Res. Dec 1971;15 Pt 4(0):277-91. [Medline].

  38. Sohner L, Mitchell P. Phonatory and phonetic characteristics of prelinguistic vocal development in cri du chat syndrome. J Commun Disord. Feb 1991;24(1):13-20. [Medline].

  39. South ST, Swensen JJ, Maxwell T, Rope A, Brothman AR, Chen Z. A new genomic mechanism leading to cri-du-chat syndrome. Am J Med Genet A. Dec 15 2006;140(24):2714-20. [Medline].

  40. Wilkins LE, Brown JA, Nance WE, Wolf B. Clinical heterogeneity in 80 home-reared children with cri du chat syndrome. J Pediatr. Apr 1983;102(4):528-33. [Medline].

  41. Wilkins LE, Brown JA, Wolf B. Psychomotor development in 65 home-reared children with cri-du-chat syndrome. J Pediatr. Sep 1980;97(3):401-5. [Medline].

  42. Zhang X, Snijders A, Segraves R, et al. High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative genomic hybridization. Am J Hum Genet. Feb 2005;76(2):312-26. [Medline].

 
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Infant with cri-du-chat syndrome. Note the round face with full cheeks, hypertelorism, epicanthal folds, and apparently low-set ears.
Child with cri-du-chat syndrome. Note the hypertonicity, small and narrow face, dropped jaw, and open-mouth expression secondary to facial laxity.
Fluorescent in situ hybridization (FISH) study of a patient with cri-du-chat syndrome. FISH photograph shows deletion of a locus-specific probe for the cri-du-chat region. Spectrum orange color represents chromosome 5–specific signal and spectrum green is cri-du-chat locus signal. Absence of a green signal indicates monosomy for that region (left, interphase cell; right, metaphase chromosome spread).
G-banded karyotype [46,XX,del(5)(p13)].
G-banded karyotype of a carrier father [46,XY,t(5;17)(p13.3;p13)].
 
 
 
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