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.

Read more about enlarged parietal foramina.

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

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.

Read more about the ALX4 and EXT2 genes and chromosome 11.

See a list of genes associated with Potocki-Shaffer syndrome.

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.