Potocki-Shaffer Syndrome

Potocki -Shaffer syndrome is a skeletal malformation syndrome characterized by exostoses, often intellectual disability and cranio-fascial abnormalities. The cause is a deletion of genes in locus 11p11.2 on chromosome 11. Treatment is purely symptomatic and is limited to measures such as early intervention.

Potocki-Shaffer Syndrome

What is Potocki-Shaffer Syndrome?

Monosomies are variants of genome mutation in which a single chromosome of the diploid chromosome set is missing. While almost all monosomies are fetal lethal, deletion of autosomes can produce a viable individual. Accordingly, deletions of autosomes are to be distinguished from monosomy, although both errors in the genome are closely related. See healthknowing for What is the Definition of Diabetic Ketoacidosis.

Potocki-Shaffer syndrome is a genetic syndrome that is based on a chromosomal mutation with a deletion of several neighboring genes. The syndrome involves various changes in the skeletal system and is rather rare. The frequency is estimated to be less than 1 case in 1,000,000. Up to 2006, 23 patients from 14 different families were described.

A maximum of 100 cases have been documented since the first description. The skeletal disorder was first described in 1996. Potocki and Shaffer are considered to be the first to describe it. Due to the small number of cases, the research situation is limited. However, the causative mutation could already be detected despite the small number of cases.


The cause of Potocki-Shaffer syndrome lies in the genes. Familial accumulation has been observed in the cases documented so far. Those affected can therefore inherit the disorder from one of their parents. In these cases, the inheritance corresponds to an autosomal dominant inheritance. In the majority of all cases, however, there is no hereditary basis.

The syndrome is caused by the deletion of neighboring genes of gene section 11p11.2 on chromosome 11. In most cases, deletion occurs during the formation of parental gametes or germ cells. More rarely, the gene loss occurs in the early fetal development of the embryo.

The deletion can affect the EXT2 gene, the loss of which causes exostoses. EXT2 encodes the protein exostosin-2, which binds to the protein exostosin-1 within the Golgi apparatus and affects the formation of heparan sulfate. A deletion of ALX4 can also cause the syndrome. This gene encodes transcription factors for skull development, the loss of which results in an enlarged fontanelle.

A PHF21A deletion may also be present. PHF21A encodes BHC80, which is involved in the BHC corepressor complex and thus mediates gene regulation for nerve cells. The involvement of other genes from the same section cannot be ruled out.

Symptoms, Ailments & Signs

Potocki-Shaffer syndrome is characterized by different symptoms, the occurrence of which depends on the gene that has been deleted. In most cases, patients with the syndrome suffer from numerous exostoses and a parietal foramina, i.e. an additional opening in the area of ​​the parietal bone. Many sufferers have enlarged fontanelles.

The anterior fontanelle is affected in most cases. In individual cases, there may be a reduction in intelligence, which is often accompanied by a developmental delay. Anomalies in the craniofacial region, which correspond to malformations of the facial skeleton, occasionally occur.

These malformations include, for example, short heads in the sense of brachycephaly. The syndrome can also manifest itself in a pronounced forehead, a narrow bridge of the nose or a shortened distance between the mouth and nose. The latter phenomenon is also known as narrow philtrum. In individual cases, the symptoms described are associated with drooping corners of the mouth. Visual disturbance or renal and urinary organ malformations have been documented but are rare.

Diagnosis & course of disease

The diagnosis of Potocki-Shaffer syndrome is made on the basis of anamnesis and clinical picture based on the symptoms. Definitive evidence of a genetic disorder can be cytogenetic by fluorescence in situ hybridization or FISH testing. Molecular genetic proof of the causative deletion is also available.

In some cases, the parents of affected children are recommended to be examined for balanced translocations, which should allow them to assess the risk of developing the disease in later children. The prognosis of patients with Potocki-Shaffer syndrome depends on the symptoms and their extent in the individual case.

The risk of malignant degeneration of the exostoses also determines the prognosis. The risk of malignant cancer is considered to be increased for patients. Nevertheless, malignant degeneration in the context of the syndrome is rather rare.

When should you go to the doctor?

Potocki-Shaffer syndrome is usually diagnosed immediately after birth. Further investigations show the severity of the genetic defect. Regular visits to the doctor are indicated during treatment. Among other things, the child must be presented to a specialist for genetic diseases. In addition, ear doctors, ophthalmologists and orthopedists must be consulted to treat the individual symptoms of the ears, eyes and skeletal muscles. If there are cases of Potocki-Shaffer syndrome in the family, a genetic test should be carried out in the event of a new pregnancy. Genetic counseling is also recommended.

The parents of an affected child should also be examined for balanced translocations so that the risk of a recurrence in later offspring can be assessed. After the major ailments have been treated, the children can lead relatively unaffected lives. Nevertheless, one should visit the pediatrician regularly so that the course of the disease can be monitored. If the symptoms get worse, a doctor’s visit is recommended. In individual cases, serious complications can also occur, for example in the case of attacks of fatigue in dangerous situations. Parents should always carry a mobile phone with them so that an ambulance can be called immediately in the event of an accident.

Treatment & Therapy

A causal therapy is not yet available for patients with Potocki-Shaffer syndrome. The syndrome is the result of a genetic deletion. For this reason, gene therapy approaches could possibly offer causal treatment options in the future. So far, however, gene therapy approaches are not in the clinical phase.

Since no causal therapy is available for patients with the syndrome, treatment focuses on supportive measures. The systematic and regular search for any visual disturbances, such as squinting or nystagmus, is recommended. In addition, patients are advised to regularly check for hearing disorders.

In addition, regular monitoring of the exostoses is indicated in order to be able to identify and treat malignant degeneration in good time. If there is a heart defect or other organ malformations, invasive procedures are usually used to correct them, which in individual cases can be combined with medical follow-up treatment. In the case of intellectual disability or developmental delay, patients are advised to seek early support.


The Potocki-Shaffer syndrome cannot yet be completely prevented. Genetic counseling in the phase of family planning can be understood in the broadest sense as a preventive step. Other prophylaxis are not available.


After the initial treatment of the rare Potocki-Shaffer syndrome, there is only a symptomatic form of follow-up care. In addition, the parents of sick children should take advantage of genetic counseling with regard to family planning. In order to closely monitor further progress, constant monitoring of hearing and visual performance is recommended. Doctors also recommend having your bones checked regularly.

Parents should keep all check-up appointments in order to identify further complaints in good time. Typically, there is psychological stress in the family in connection with this disease. Therefore, affected families should consult a psychotherapist. There are no self-help groups for this syndrome in Germany, but sensitive psychotherapeutic treatment is valuable support.

As part of the follow-up treatment, it is also worth thinking about early support for the sick children. This helps the children and parents to cope with everyday life. Depending on how the condition is sold, organ functions may be compromised. This is exactly why it is so important to keep regular medical check-ups so that you can react early if necessary. Lovingly dealing with the sick children and the solidarity of relatives and friends can alleviate the problems and have a positive effect on the mood within the family.

You can do that yourself

There is no cure for this extremely rare disease. However, depending on how the syndrome presents itself, symptomatic treatments are initiated by the doctor. If there is a heart or other organ defect, the doctors will recommend the appropriate operations. Parents of affected children can also ensure that early support is as intensive as possible.

Since the disease can progress, regular hearing and visual checks are recommended. The bones of those affected should also be examined again and again in order to be able to detect any degeneration at an early stage. If the parents of a child with Potocki-Shaffer syndrome want to have another child, genetic testing is recommended so that the risk can be assessed as to whether the next child will also be born with the syndrome.

Potocki-Shaffer Syndrome can be very distressing for both parents and sufferers. In this case, psychotherapeutic treatment is recommended. A self-help group would also be advisable, but because the disease is so rare, there are none in Germany. Only in Orpha Net, the portal for rare diseases, is there constantly updated further information (www.orpha.net), with which those affected and those interested can always keep up to date.