ClinGen Dosage Sensitivity Curation Page

5p15 terminal (Cri du chat syndrome) region

  • Curation Status: Complete
  • id: ISCA-37390
  • Date last evaluated: 2016-06-21
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 2


Location Information

Select assembly: (NC_000005.9) ()
Evidence for haploinsufficiency phenotype
PubMed ID Description
15635506 Zhang, et al. (2005) characterize the 5p deletions using CGH array for 94 patients with Cri du Chat syndrome. Their results confirm that deletion of the distal 11.3 Mb of 5p are associated with speech delay, a cat-like cry and high pitched voice, distinctive facial features, and variable intellectual disability that is described in patients with Cri du Chat syndrome. In addition, they provide genotype-phenotype data regarding genomic regions associated with variable degrees of intellectual disability in patients with larger deletions.
11238681 Cerruti Mainardi, et al. (2001) provide genotype-phenotype data for 80 patients with Cri du Chat syndrome and deletions on 5p using FISH. Their results are consistent with those of Zhang et al.

Haploinsufficiency phenotype comments:

Large 5p deletions of variable size, both terminal and interstitial, lead to Cri du Chat syndrome. While the breakpoints defined for this region include the regions on 5p that have been strongly associated with speech delay, cat-like cry/high-pitched voice, characteristic facial features, and variable intellectual disability, there are patients with smaller deletions or which overlap to a variable degree which may exhibit some or all of these clinical features or may be clinically unaffected. Clinical correlation and additional literature evaluation will be required to assess smaller deletions. See also PMIDs: 15602631 and 24556499.

  • Triplosensitivity score: 2
  • Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Duplications of this precisely defined region of terminal 5p have not been described but there are rare reports of patients with smaller or larger duplication, some of whom also have deletions of 5p material as well. Vust, et al. (2002, PMID:12030892) report a patient with a maternally inherited duplication at 5p15.3 that does not include the "Cri du Chat critical region" at 5p15.2. This patient had mild dysmorphic features and neurodevelopmental problems, but also had prenatal alcohol exposure. Her mother had a probable learning disability and mental health concerns. The clinical assessment of the duplication was complicated by the family's difficult social situation. Reports of larger duplication include Zenger-Hain, et al. (1993, PMID:8291556) and Cervera et al. (2005, PMID:16001443) in patients with dysmorphic facial features and developmental disabilities, as well as several reports of duplication of the whole p-arm. See de Carvalho et al (PMID 18777129) for a description of a larger (~20 Mb) 5pter-5p13.3 duplication segregating in a large family. Affected individuals all presented abnormal phenotypes including hypotonia, intellectual disability, and dysmorphic facial features. Sheen et al (PMID 12654978) report an individual (proband 2) with a smaller 5p15.3 duplication and periventricular heterotopia, seizures, congenital anomalies, hypotonia, and other features. Baialardo et al (PMID 14564214) report a smaller duplication in a relatively unaffected individual, however the size of the duplication was not molecularly defined and the banding quality was poor. In general, the larger the duplication the more severe the patient's phenotype. However, a clearly defined syndrome has not been described in association with a duplication of the terminal 11.3 Mb of 5p.