Potocki-Shaffer syndrome is a disorder that affects the development of the bones, brain, and other tissues. The signs and symptoms of Potocki-Shaffer syndrome vary widely among affected individuals.

People with Potocki-Shaffer syndrome have enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. Openings in the parietal bones are normal during fetal development, but they usually close before birth. In people with this condition, the parietal foramina are larger than normal and may remain open after birth. Affected individuals often have a wide, short skull (brachycephaly). Their head size may be normal or unusually small.

Most people with Potocki-Shaffer syndrome have multiple noncancerous (benign) bone tumors called osteochondromas. In rare instances, these tumors become cancerous.

Other features of Potocki-Shaffer syndrome include intellectual disabilities, recurrent seizures (epilepsy), and delayed development of speech and motor skills (such as sitting and walking).

Many people with Potocki-Shaffer syndrome have distinctive facial features, such as a broad and tall forehead, a prominent bridge of the nose, a narrow distance between the nose and upper lip (a short philtrum), a short nose with a wide tip, and a downturned mouth.

Less commonly, Potocki-Shaffer syndrome causes vision problems; additional skeletal abnormalities; and defects in the heart, kidneys, and urinary tract.

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

Potocki-Shaffer syndrome is caused by a deletion of genetic material from the short (p) arm of chromosome 11 at a position designated 11p11.2. Because of this change, Potocki-Shaffer syndrome is also known as proximal 11p deletion syndrome. The term "proximal" means that the missing piece is near the center of the chromosome. The size of the deletion varies among affected individuals. Studies suggest that an individual would need a deletion of at least 2.1 million DNA building blocks (base pairs), also written as 2.1 megabases (Mb), to develop all of the features associated with the condition. The loss of multiple genes within the deleted region causes the signs and symptoms of Potocki-Shaffer syndrome.

In particular, the deletion of the ALX4, PHF21A, and EXT2 genes is associated with several of the characteristic features of Potocki-Shaffer syndrome. The ALX4 and PHF21A proteins are involved in regulating the activity of genes, particularly those that play a role in the development of the brain, skull, and face. The EXT2 gene provides instructions for making a protein that modifies another protein that helps control the formation and growth of bones.

The deletion of the ALX4 gene causes the enlarged parietal foramina found in people with this condition. In addition, the loss of the PHF21A gene is the cause of intellectual disabilities and distinctive facial features in affected individuals. The deletion of the EXT2 gene is associated with the development of multiple osteochondromas. The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome.

Genetic Testing Information

• Genetic Testing Registry: Potocki-Shaffer syndrome

Genetic and Rare Diseases Information Center

• Potocki-Shaffer syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• POTOCKI-SHAFFER SYNDROME

Scientific Articles on PubMed

• PubMed

• 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. Citation on PubMed or Free article on PubMed Central
• 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 Jan;161A(1):198-202. doi: 10.1002/ajmg.a.35671. Epub 2012 Dec 13. Citation on PubMed
• Poole RL, Bijlsma EK, Houge G, Jones G, Mikstiene V, Preiksaitiene E, Thompson L, Tatton-Brown K. The PHF21A neurodevelopmental disorder: an evaluation of clinical data from 13 patients. Clin Dysmorphol. 2023 Apr 1;32(2):49-54. doi: 10.1097/MCD.0000000000000455. Epub 2023 Feb 21. Citation on PubMed
• 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. doi: 10.5414/npp26001. Citation on PubMed
• 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. Citation on PubMed
• Trajkova S, Di Gregorio E, Ferrero GB, Carli D, Pavinato L, Delplancq G, Kuentz P, Brusco A. New Insights into Potocki-Shaffer Syndrome: Report of Two Novel Cases and Literature Review. Brain Sci. 2020 Oct 28;10(11):788. doi: 10.3390/brainsci10110788. Citation on PubMed
• Wuyts W, Waeber G, Meinecke P, Schuler 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. doi: 10.1038/sj.ejhg.5201163. Citation on PubMed