Search tips
Search criteria 


Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Med Genet. 2001 March; 38(3): 151–158.
PMCID: PMC1734829

Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation


The majority of deletions of the short arm of chromosome 5 are associated with cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic variability. To perform a genotype-phenotype correlation, 80 patients from the Italian CdCS Register were analysed. Molecular cytogenetic analysis showed that 62 patients (77.50%) had a 5p terminal deletion characterised by breakpoint intervals ranging from p13 (D5S763) to p15.2 (D5S18). Seven patients (8.75%) had a 5p interstitial deletion, four (5%) a de novo translocation, and three (3.75%) a familial translocation. Of the remaining four patients, three (3.75%) had de novo 5p anomalies involving two rearranged cell lines and one (1.25%) had a 5p deletion originating from a paternal inversion. The origin of the deleted chromosome 5 was paternal in 55 out of 61 patients (90.2%). Genotype-phenotype correlation in 62 patients with terminal deletions highlighted a progressive severity of clinical manifestation and psychomotor retardation related to the size of the deletion. The analysis of seven patients with interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731. Furthermore, this study lends support to the hypothesis of a separate region in p15.3 for the speech delay.

Keywords: cri du chat syndrome; 5p deletion; phenotype-genotype correlation; FISH

Full Text

The Full Text of this article is available as a PDF (161K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Overhauser J, Huang X, Gersh M, Wilson W, McMahon J, Bengtsson U, Rojas K, Meyer M, Wasmuth JJ. 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. 1994 Feb;3(2):247–252. [PubMed]
  • Breg WR, Steele MW, Miller OJ, Warburton D, DeCapoa A, Allderdice PW. The cri du chat syndrome in adolescents and adults: clinical finding in 13 older patients with partial deletion of the short arm of chromosome No. 5(5p-). J Pediatr. 1970 Nov;77(5):782–791. [PubMed]
  • Niebuhr E. The cat cry syndrome (5p-) in adolescents and adults. J Ment Defic Res. 1971 Dec;15(Pt 4)(0):277–291. [PubMed]
  • Cerruti Mainardi P, Vianello MG, Bonioli E. Considerazioni su cinque casi di sindrome di "cri du chat". Minerva Pediatr. 1976 Dec 1;28(38):2389–2400. [PubMed]
  • Niebuhr E. The Cri du Chat syndrome: epidemiology, cytogenetics, and clinical features. Hum Genet. 1978 Nov 16;44(3):227–275. [PubMed]
  • Wilkins LE, Brown JA, Nance WE, Wolf B. Clinical heterogeneity in 80 home-reared children with cri du chat syndrome. J Pediatr. 1983 Apr;102(4):528–533. [PubMed]
  • Van Buggenhout GJ, Pijkels E, Holvoet M, Schaap C, Hamel BC, Fryns JP. Cri du chat syndrome: changing phenotype in older patients. Am J Med Genet. 2000 Jan 31;90(3):203–215. [PubMed]
  • Higurashi M, Oda M, Iijima K, Iijima S, Takeshita T, Watanabe N, Yoneyama K. Livebirth prevalence and follow-up of malformation syndromes in 27,472 newborns. Brain Dev. 1990;12(6):770–773. [PubMed]
  • 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. 1995 May;56(5):1162–1172. [PubMed]
  • Niebuhr E. Cytologic observations in 35 individuals with a 5p- karyotype. Hum Genet. 1978 Jun 9;42(2):143–156. [PubMed]
  • Kushnick T, Rao KW, Lamb AN. Familial 5p- syndrome. Clin Genet. 1984 Nov;26(5):472–476. [PubMed]
  • Baccichetti C, Lenzini E, Artifoni L, Caufin D, Marangoni P. Terminal deletion of the short arm of chromosome 5. Clin Genet. 1988 Oct;34(4):219–223. [PubMed]
  • Overhauser J, Golbus MS, Schonberg SA, Wasmuth JJ. Molecular analysis of an unbalanced deletion of the short arm of chromosome 5 that produces no phenotype. Am J Hum Genet. 1986 Jul;39(1):1–10. [PubMed]
  • Gersh M, Goodart SA, Pasztor LM, Harris DJ, Weiss L, Overhauser J. Evidence for a distinct region causing a cat-like cry in patients with 5p deletions. Am J Hum Genet. 1995 Jun;56(6):1404–1410. [PubMed]
  • Simmons AD, Püschel AW, McPherson JD, Overhauser J, Lovett M. Molecular cloning and mapping of human semaphorin F from the Cri-du-chat candidate interval. Biochem Biophys Res Commun. 1998 Jan 26;242(3):685–691. [PubMed]
  • Church DM, Yang J, Bocian M, Shiang R, Wasmuth JJ. A high-resolution physical and transcript map of the Cri du chat region of human chromosome 5p. Genome Res. 1997 Aug;7(8):787–801. [PubMed]
  • Zhou J, Liyanage U, Medina M, Ho C, Simmons AD, Lovett M, Kosik KS. Presenilin 1 interaction in the brain with a novel member of the Armadillo family. Neuroreport. 1997 May 27;8(8):2085–2090. [PubMed]
  • Medina M, Marinescu RC, Overhauser J, Kosik KS. Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome. Genomics. 2000 Jan 15;63(2):157–164. [PubMed]
  • Niebuhr E. Anthropometry in the Cri du Chat syndrome. Clin Genet. 1979 Aug;16(2):82–95. [PubMed]
  • Cornish KM, Bramble D, Munir F, Pigram J. Cognitive functioning in children with typical cri du chat (5p-) syndrome. Dev Med Child Neurol. 1999 Apr;41(4):263–266. [PubMed]
  • 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. 1999 Jul;36(7):567–570. [PMC free article] [PubMed]
  • Mills JL, Kirke PN, Molloy AM, Burke H, Conley MR, Lee YJ, Mayne PD, Weir DG, Scott JM. Methylenetetrahydrofolate reductase thermolabile variant and oral clefts. Am J Med Genet. 1999 Sep 3;86(1):71–74. [PubMed]
  • Marinescu RC, Johnson EI, Grady D, Chen XN, Overhauser J. FISH analysis of terminal deletions in patients diagnosed with cri-du-chat syndrome. Clin Genet. 1999 Oct;56(4):282–288. [PubMed]
  • Winter RM, Baraitser M. Malformation syndromes--a diagnostic approach. Arch Dis Child. 1984 Apr;59(4):294–295. [PMC free article] [PubMed]
  • Frankenburg WK, Dodds J, Archer P, Shapiro H, Bresnick B. The Denver II: a major revision and restandardization of the Denver Developmental Screening Test. Pediatrics. 1992 Jan;89(1):91–97. [PubMed]
  • Cerruti Mainardi P, Guala A, Pastore G, Pozzo G, Dagna Bricarelli F, Pierluigi M. Psychomotor development in Cri du Chat Syndrome. Clin Genet. 2000 Jun;57(6):459–461. [PubMed]
  • Carlock LR, Wasmuth JJ. Molecular approach to analyzing the human 5p deletion syndrome, cri du chat. Somat Cell Mol Genet. 1985 May;11(3):267–276. [PubMed]
  • Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. [PubMed]
  • Perfumo C, Cerruti Mainardi P, Calí A, Coucourde G, Zara F, Cavani S, Overhauser J, Bricarelli FD, Pierluigi M. The first three mosaic cri du chat syndrome patients with two rearranged cell lines. J Med Genet. 2000 Dec;37(12):967–972. [PMC free article] [PubMed]
  • Coplan J, Gleason JR, Ryan R, Burke MG, Williams ML. Validation of an early language milestone scale in a high-risk population. Pediatrics. 1982 Nov;70(5):677–683. [PubMed]
  • Sargent CA, Chalmers IJ, Leversha M, Affara NA. A rearrangement on chromosome 5 of an expressed human beta-glucuronidase pseudogene. Mamm Genome. 1994 Dec;5(12):791–796. [PubMed]
  • Simmons AD, Goodart SA, Gallardo TD, Overhauser J, Lovett M. Five novel genes from the cri-du-chat critical region isolated by direct selection. Hum Mol Genet. 1995 Feb;4(2):295–302. [PubMed]
  • Thompson TG, DiDonato CJ, Simard LR, Ingraham SE, Burghes AH, Crawford TO, Rochette C, Mendell JR, Wasmuth JJ. A novel cDNA detects homozygous microdeletions in greater than 50% of type I spinal muscular atrophy patients. Nat Genet. 1995 Jan;9(1):56–62. [PubMed]
  • Simmons AD, Overhauser J, Lovett M. Isolation of cDNAs from the Cri-du-chat critical region by direct screening of a chromosome 5-specific cDNA library. Genome Res. 1997 Feb;7(2):118–127. [PubMed]
  • 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. 1999 Jan 1;82(1):6–14. [PubMed]
  • Dipple KM, McCabe ER. Phenotypes of patients with "simple" Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am J Hum Genet. 2000 Jun;66(6):1729–1735. [PubMed]
  • Johnson EI, Marinescu RC, Punnett HH, Tenenholz B, Overhauser J. 5p14 deletion associated with microcephaly and seizures. J Med Genet. 2000 Feb;37(2):125–127. [PMC free article] [PubMed]
  • Hand JL, Michels VV, Marinello MJ, Ketterling RP, Jalal SM. Inherited interstitial deletion of chromosomes 5p and 16q without apparent phenotypic effect: further confirmation. Prenat Diagn. 2000 Feb;20(2):144–151. [PubMed]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group