Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Potocki-Shaffer syndrome

Reviewed October 2012

What is Potocki-Shaffer syndrome?

Potocki-Shaffer syndrome is a disorder that affects development of the bones, brain, and other organs. Most people with this condition have multiple non-cancerous (benign) bone tumors called exostoses. In rare instances, these tumors become cancerous. People with Potocki-Shaffer syndrome also have enlarged openings in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). These abnormal openings form extra "soft spots" on the head, in addition to the two that newborns normally have.

The signs and symptoms of Potocki-Shaffer syndrome vary widely. In addition to multiple exostoses and enlarged parietal foramina, affected individuals often have intellectual disability and delayed development of speech, motor skills (such as sitting and walking), and social skills. Many people with this condition have distinctive facial features, which can include a wide, short skull (brachycephaly); a prominent forehead; a narrow bridge of the nose; a shortened distance between the nose and upper lip (a short philtrum); and a downturned mouth. Less commonly, Potocki-Shaffer syndrome causes vision problems, additional skeletal abnormalities, and defects in the heart, kidneys, and urinary tract.

How common is Potocki-Shaffer syndrome?

Potocki-Shaffer syndrome is a rare condition, although its prevalence is unknown. Fewer than 100 cases have been reported in the scientific literature.

What are the genetic changes related to Potocki-Shaffer syndrome?

Potocki-Shaffer syndrome (also known as proximal 11p deletion syndrome) is caused by a deletion of genetic material from the short (p) arm of chromosome 11 at a position designated 11p11.2. The size of the deletion varies among affected individuals. Studies suggest that the full spectrum of features is caused by a deletion of at least 2.1 million DNA building blocks (base pairs), also written as 2.1 megabases (Mb). The loss of multiple genes within the deleted region causes the varied signs and symptoms of Potocki-Shaffer syndrome. In particular, deletion of the EXT2 and ALX4 genes are associated with two of the characteristic features of this condition.

Loss of the EXT2 gene causes multiple exostoses in people with Potocki-Shaffer syndrome. The EXT2 gene provides instructions for producing a protein called exostosin-2. This protein attaches (binds) to another protein, exostosin-1, to form a complex that is found in a cell structure called the Golgi apparatus. This structure modifies newly produced proteins, and the exostosin complex, in particular, modifies a protein called heparan sulfate so it can be used in the body. The 11p11.2 deletion likely leads to a reduction of exostosin-2 protein and the inability to process heparan sulfate correctly. Although heparan sulfate is involved in many body processes, it is unclear how the lack of this protein causes multiple exostoses.

Deletion of the ALX4 gene is the cause of enlarged parietal foramina in Potocki-Shaffer syndrome. The ALX4 gene provides instructions for making a protein called a transcription factor. Transcription factors attach (bind) to specific regions of DNA and help control the activity of particular genes, which is required for proper development throughout the body. The ALX4 protein seems to be critical for the complete development of the skull. A shortage of this protein, caused by the chromosome 11 deletion, impairs proper bone formation (ossification) in the skull, which results in enlarged parietal foramina.

The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome.

Related Chromosome(s)

Changes involving this chromosome are associated with Potocki-Shaffer syndrome.

  • chromosome 11

Related Gene(s)

Changes in these genes are associated with Potocki-Shaffer syndrome.

  • ALX4
  • EXT2
  • PHF21A

Can Potocki-Shaffer syndrome be inherited?

Potocki-Shaffer syndrome follows an autosomal dominant inheritance pattern, which means a deletion of genetic material from one copy of chromosome 11 is sufficient to cause the disorder.

This condition may be inherited or may occur as a result of a new chromosomal change. In some cases, an affected person inherits the chromosome with a deleted segment from a parent. More commonly, the condition results from a deletion that occurs during the formation of reproductive cells (eggs and sperm) in a parent or in early fetal development. These cases occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Potocki-Shaffer syndrome?

These resources address the diagnosis or management of Potocki-Shaffer syndrome and may include treatment providers.

  • Genetic Testing Registry: Potocki-Shaffer syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1832588)
  • MedlinePlus Health Topic: Bone Diseases (http://www.nlm.nih.gov/medlineplus/bonediseases.html)

You might also find information on the diagnosis or management of Potocki-Shaffer syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/potocki-shaffer-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Potocki-Shaffer syndrome?

You may find the following resources about Potocki-Shaffer syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Potocki-Shaffer syndrome?

  • chromosome 11p11.2 deletion syndrome
  • P11pDS
  • proximal 11p deletion syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Potocki-Shaffer syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Potocki-Shaffer syndrome?

autosomal ; autosomal dominant ; benign ; bone formation ; brachycephaly ; cell ; chromosome ; deletion ; disability ; DNA ; exostoses ; gene ; Golgi apparatus ; heparan sulfate ; inheritance ; inheritance pattern ; inherited ; Mb ; motor ; ossification ; philtrum ; prevalence ; protein ; proximal ; reproductive cells ; spectrum ; sperm ; sulfate ; syndrome ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Hall CR, Wu Y, Shaffer LG, Hecht JT. Familial case of Potocki-Shaffer syndrome associated with microdeletion of EXT2 and ALX4. Clin Genet. 2001 Nov;60(5):356-9. (http://www.ncbi.nlm.nih.gov/pubmed/11903336?dopt=Abstract)
  • Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, Talkowski ME, Ruderfer D, Lee JH, Glotzbach C, Ha K, Kjaergaard S, Levin AV, Romeike BF, Kleefstra T, Bartsch O, Elsea SH, Jabs EW, MacDonald ME, Harris DJ, Quade BJ, Ropers HH, Shaffer LG, Kutsche K, Layman LC, Tommerup N, Kalscheuer VM, Shi Y, Morton CC, Kim CH, Gusella JF. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet. 2012 Jul 13;91(1):56-72. doi: 10.1016/j.ajhg.2012.05.005. Epub 2012 Jul 5. (http://www.ncbi.nlm.nih.gov/pubmed/22770980?dopt=Abstract)
  • Romeike BF, Wuyts W. Proximal chromosome 11p contiguous gene deletion syndrome phenotype: case report and review of the literature. Clin Neuropathol. 2007 Jan-Feb;26(1):1-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17290930?dopt=Abstract)
  • 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 Mar;152A(3):565-72. doi: 10.1002/ajmg.a.33245. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20140962?dopt=Abstract)
  • Wakui K, Gregato G, Ballif BC, Glotzbach CD, Bailey KA, Kuo PL, Sue WC, Sheffield LJ, Irons M, Gomez EG, Hecht JT, Potocki L, Shaffer LG. 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 May;13(5):528-40. (http://www.ncbi.nlm.nih.gov/pubmed/15852040?dopt=Abstract)
  • Wuyts W, Waeber G, Meinecke P, Schüler H, Goecke TO, Van Hul W, Bartsch O. Proximal 11p deletion syndrome (P11pDS): additional evaluation of the clinical and molecular aspects. Eur J Hum Genet. 2004 May;12(5):400-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14872200?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2012
Published: August 18, 2014