J Korean Med Sci.  2015 Feb;30(2):214-217. 10.3346/jkms.2015.30.2.214.

The First Korean Patient with Potocki-Shaffer Syndrome: A Rare Cause of Multiple Exostoses

• Sohn YB
• Yim SY
• Cho EH
• Kim OH

• KMID: 2129654
• DOI: http://doi.org/10.3346/jkms.2015.30.2.214

Abstract

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)x1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

Keyword

Potocki-Shaffer Syndrome; Chromosomal Microarray; Multiple Exostosis; Parietal Foramina

MeSH Terms

Child
Chromosome Deletion
Chromosome Disorders/diagnosis/*genetics/radiography
Chromosome Mapping
Chromosomes, Human, Pair 11/genetics/radiography
Craniofacial Abnormalities/genetics
Developmental Disabilities/genetics
Exostoses, Multiple Hereditary/diagnosis/*genetics/radiography
Humans
Male
Muscle Hypotonia/genetics
Oligonucleotide Array Sequence Analysis
Rare Diseases/*genetics
Republic of Korea

Figure

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  Fig. 1 Skeletal survey of long bones at age 6 yr. Multiple exostoses (arrows) of the metadiaphyseal portion of the humerus (A), wrists (B), and proximal femora (C) and at the distal femora and proximal tibia and fibula are evident.

• 

  Fig. 2 Serial changes of biparietal foramena in the skull. Frontal (A) and Lateral (B) radiographs taken at age 4 months. Large biparietal foramina are noted (arrows). 3-D reconstruction image (C) of the skull at age 4 months shows enlarged biparietal foramina acrossing midline (arrows). Follow up skull 3-D reconstruction image (D) at age 8 yr shows persistent biparietal foramina (arrows).

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  Fig. 3 Result of chromosomal microarray. The red bar indicates an 8.6 Mb deletion at 11p11.2p12 including EXT2, ALX4, and PHF21A.

Reference

1. Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK, Powell CM, et al. Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, and mental retardation, caused by deletions in the short arm of chromosome 11. Am J Hum Genet. 1996; 58:734–742.

2. Swarr DT, Bloom D, Lewis RA, Elenberg E, Friedman EM, Glotzbach C, Wissman SD, Shaffer LG, Potocki L. Potocki-Shaffer syndrome: comprehensive clinical assessment, review of the literature, and proposals for medical management. Am J Med Genet A. 2010; 152a:565–572.

3. Potocki L, Shaffer LG. Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses (EXT2). Am J Med Genet. 1996; 62:319–325.

4. Montgomery ND, Turcott CM, Tepperberg JH, McDonald MT, Aylsworth AS. A 137-kb deletion within the Potocki-Shaffer syndrome interval on chromosome 11p11.2 associated with developmental delay and hypotonia. Am J Med Genet A. 2013; 161a:198–202.

5. Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, Hecht JT, Lovett M, Evans GA. The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nat Genet. 1996; 14:25–32.

6. Hall CR, Wu Y, Shaffer LG, Hecht JT. Familial case of Potocki-Shaffer syndrome associated with microdeletion of EXT2 and ALX4. Clin Genet. 2001; 60:356–359.

7. Wakui K, Gregato G, Ballif BC, Glotzbach CD, Bailey KA, Kuo PL, Sue WC, Sheffield LJ, Irons M, Gomez EG, et al. Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome. Eur J Hum Genet. 2005; 13:528–540.

8. Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, et al. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet. 2012; 91:56–72.

9. Bovée JV. Multiple osteochondromas. Orphanet J Rare Dis. 2008; 3:3.

10. Busse M, Feta A, Presto J, Wilén M, Grønning M, Kjellén L, Kusche-Gullberg M. Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation. J Biol Chem. 2007; 282:32802–32810.

11. Feta A, Do AT, Rentzsch F, Technau U, Kusche-Gullberg M. Molecular analysis of heparan sulfate biosynthetic enzyme machinery and characterization of heparan sulfate structure in Nematostella vectensis. Biochem J. 2009; 419:585–593.

12. Jones KB. Glycobiology and the growth plate: current concepts in multiple hereditary exostoses. J Pediatr Orthop. 2011; 31:577–586.

13. Hameetman L, David G, Yavas A, White SJ, Taminiau AH, Cleton-Jansen AM, Hogendoorn PC, Bovée JV. Decreased EXT expression and intracellular accumulation of heparan sulphate proteoglycan in osteochondromas and peripheral chondrosarcomas. J Pathol. 2007; 211:399–409.

14. Wu YQ, Badano JL, McCaskill C, Vogel H, Potocki L, Shaffer LG. Haploinsufficiency of ALX4 as a potential cause of parietal foramina in the 11p11.2 contiguous gene-deletion syndrome. Am J Hum Genet. 2000; 67:1327–1332.