ClinGen Dosage Sensitivity Curation Page

11p11.2 (Potocki-Shaffer syndrome) region (includes ALX4, EXT2)

  • Curation Status: Complete
  • id: ISCA-37441
  • Date last evaluated: 2013-12-12
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 0

Location Information

Select assembly: (NC_000011.9) ()
Evidence for haploinsufficiency phenotype
PubMed ID Description
15852040 Wakui et al. (2005) compare deletion size and phenotype in 10 individuals affected with Potocki-Shaffer syndrome (PSS). Full spectrum of PSS is seen in individuals with deletions at least 2.1 Mb (chr11:43894800-46152450 [hg19]), including both ALX4 and EXT2. ALX4 haploinsufficiency results in parietal foramina and EXT2 haploinsufficiency results in exostoses.
16319823 Mavrogiannis et al. (2006) describe mutations in homeobox genes ALX4 and MSX2 causing craniosynostosis. In this study, they identified a three-generation family with a deletion on chr11:40406581-44924293 [hg19], which includes the ALX4 and EXT2 genes manifesting enlarged parietal foramina and exostoses of the long bones. This family did not have intellectual disability, and by STR and FISH mapping the deletion of this family against other reported deletions in the literature, the authors propose that the gene(s) involved in this phenotype are proximal to EXT2 in PSS subjects.
20140962 Swarr et al. (2010) provide a comprehensive clinical description of PSS based on meta analysis of 6 individuals with cytogenetically defined 11p deletions and review of the literature. While the deletions were of various sizes and linear positions, all included ALX4 and EXT2, accounting for the cardinal features of craniofacial anomalies, enlarged parietal foramina, and exostoses of the long bones. The authors also make evaluation and maintenance recommendations for PSS individuals based on the primary clinical findings.

Haploinsufficiency phenotype comments:

Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome with clinical features including developmental delay, mental retardation, multiple exostoses, parietal foramina, enlarged anterior fontanel, minor craniofacial anomalies, ophthalmologic anomalies, and genital abnormalities in males. Though a definitive critical region for this syndrome has not been determined, the coordinates used here are those proposed by Wakui et al (2005) (PMID:15852040): chr11:43894800-46152450 (hg19).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity