Potocki-Shaffer syndrome is a skeletal malformation syndrome characterized by exostoses, often intelligence deficiency, and craniofacial abnormalities. It is caused by a deletion of genes in locus 11p11.2 on chromosome 11. Treatment is purely symptomatic supportive and limited to measures such as early intervention.
What is Potocki-Shaffer syndrome?
Monosomies are variants of genomic mutation in which a single chromosome of the diploid chromosome set is missing. While almost all monosomies are fetally lethal, deletion of autosomes can produce a viable individual. Deletions of autosomes should therefore be distinguished from monosomy, although the two errors are closely related in the genome. Potocki-Shaffer syndrome is a genetic syndrome that is based on a chromosomal mutation with a deletion of several neighboring genes. The syndrome results in various skeletal system alterations and is rather rare. The incidence is estimated to be less than one case in 1,000,000. 23 patients have been described from 14 different families as of 2006. A total of no more than 100 cases have been documented since the initial description. Skeletal disorder was first described in 1996. Potocki and Shaffer are considered the initial describers. Due to the small number of cases, research is limited. However, the causative mutation has already been demonstrated despite the small number of cases.
Causes
The cause of Potocki-Shaffer syndrome lies in the genes. Familial clustering has been observed in the cases documented to date. Thus, affected individuals may inherit the disorder from one parent. The mode of inheritance in these cases corresponds to an autosomal dominant mode of inheritance. In the majority of cases, however, there is no hereditary basis. The syndrome is caused by deletion of adjacent genes of gene segment 11p11.2 on chromosome 11. In most cases, the deletion occurs during the formation of parental gametes or germ cells. Less commonly, the gene loss occurs during early fetal development of the embryo. The deletion may affect the gene EXT2, 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. Deletion of ALX4 can also cause the syndrome. This gene encodes transcription factors for cranial development, with loss resulting in an enlarged fontanel. In addition, a PHF21A deletion may be present. PHF21A encodes BHC80, which is involved in the corepressor complex BHC and thus mediates gene regulation for neurons. Involvement of other genes of the same section is not excluded.
Symptoms, complaints, and signs
Potocki-Shaffer syndrome is characterized by a variety of symptoms, each of which depends on the deleted gene. In most cases, patients with the syndrome suffer from numerous exostoses and parietal foramina, which is an extra opening in the parietal bone. Many affected individuals have enlarged fontanelles. The anterior fontanel is affected in most cases. In individual cases, a decrease in intelligence may be present, often accompanied by developmental delay. In the craniofacial region, anomalies corresponding to malformations of the facial skull occasionally occur. These malformations include, for example, short-headedness in the sense of brachycephaly. Equally well, the syndrome may manifest itself in a pronounced forehead, a narrow nasal bridge, 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. Impaired vision or renal and urinary organ malformations have been documented, but occur rather rarely.
Diagnosis and course of the disease
The diagnosis of Potocki-Shaffer syndrome is made on the basis of history and clinical presentation based on symptoms. Definitive evidence of a genetic disorder can be obtained cytogenetically by fluorescence in situ hybridization or FISH testing. Molecular genetic detection of the causative deletion is also available. In some cases, testing for balanced translocations is recommended for parents of affected children to assess the risk of disease in subsequent children.The prognosis of patients with Potocki-Shaffer syndrome depends on the symptoms and their extent in each individual case. The risk for malignant degeneration of the exostoses is also prognosis-determining. Patients are considered to be at increased risk for malignant cancer. Nevertheless, malignant degeneration is rather rare in the context of the syndrome.
When should one go to the doctor?
Potocki-Shaffer syndrome is usually diagnosed immediately after birth. Further testing reveals the severity of the genetic defect. Regular doctor visits are indicated during treatment. Among other things, the child must see a specialist in genetic diseases. In addition, ear specialists, ophthalmologists and orthopedists must be consulted to treat the individual symptoms of the ears, eyes and skeletal muscles. If cases of Potocki-Shaffer syndrome have already occurred in the family, genetic testing should be performed if the pregnancy is repeated. Accompanying genetic counseling is recommended. The parents of an affected child should also be screened for balanced translocations so that the risk of recurrence in subsequent offspring can be assessed. After the major symptoms have been treated, children can lead relatively symptom-free lives. However, regular visits to the pediatrician should be made so that the course of the disease can be monitored. If the symptoms become more severe, a visit to the doctor is recommended. In individual cases, serious complications can also occur, for example in the case of fatigue attacks in dangerous situations. Parents should always carry a cell phone so that the emergency doctor can be called immediately in the event of an accident.
Treatment and therapy
Causative 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 may offer causal treatment options in the future. To date, however, gene therapy approaches are not in the clinical phase. Since no causal therapy is available for patients with the syndrome, treatment is focused on supportive measures. Systematic and regular search for any visual disorders, such as strabismus or nystagmus, is considered recommended. Patients are also advised to regularly search for hearing disorders. Furthermore, regular control of exostoses is indicated in order to detect and treat malignant degeneration in time. If a heart defect or other organ malformations are present, invasive procedures are usually used for correction, which may be combined with drug follow-up treatment in individual cases. If there is a decrease in intelligence or developmental delay, patients are advised to receive early intervention.
Prevention
Potocki-Shaffer syndrome cannot be completely prevented to date. Genetic counseling during the family planning phase can be understood in the broadest sense as a preventive step. No other prophylaxis is available.
Follow-up
After initial treatment of rare Potocki-Shaffer syndrome, there is only a symptomatic form of follow-up. In addition, parents of affected children should seek genetic counseling regarding family planning. In order to closely monitor further progress, constant checks of hearing and vision are recommended. Furthermore, doctors advise to have the bones examined regularly. Parents should keep all check-up appointments in order to detect further complaints in time. Typically, psychological stress in the family occurs in connection with this disease. Therefore, affected families should contact a psychotherapist. In Germany, there are no self-help groups for this syndrome, but empathetic psychotherapeutic treatment is a valuable support. As part of the follow-up treatment, it is also worth considering early intervention for the affected children. This helps the children and parents to cope with everyday life. Depending on how the disease is sold, organ functions can be impaired. This is exactly why it is so important to keep regular medical check-ups, so that we can react at an early stage if necessary. The loving treatment of the sick children and the cohesion of relatives and friends can alleviate the problems and has a positive effect on the mood within the family.
You can do it yourself
A cure for this extremely rare condition is not possible. However, depending on how the syndrome manifests itself, symptomatic treatments will be initiated by doctors. If a heart or other organ defect is present, doctors will advise the appropriate surgeries. Parents of affected children can also provide the most intensive early intervention possible. Since the disease can progress, regular checks of hearing and vision are advised. The bones of affected children should also be examined regularly in order to detect possible degenerations at an early stage. If the parents of a child with Potocki-Shaffer syndrome wish 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 become a great burden for both the parents and the affected person. 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, there is constantly updated further information (www.orpha.net), with which those affected and interested can always keep up to date.
