Pena-Shokeir syndrome is a serious genetic disorder with multiple malformations of internal and external organs. If the infants are born alive, death occurs after a few days or weeks at the latest. The main cause of death is severe pulmonary hypoplasia.
What is Pena-Shokeir syndrome?
Pena-Shokeir syndrome is a very rare serious disorder characterized by underdevelopment of all organs. The syndrome is incompatible with life. Children born alive die after a few weeks at the latest. So far, only about 100 cases have been described. However, it is assumed that it is not a uniform disease. Various genetic defects are suspected, some of which have not yet been verified. Also, the risk for offspring to suffer from this disease, if cases have already occurred in the family or relatives, cannot be precisely stated. According to current findings, the probability should be between 0.1 and 25 percent. Since the symptoms are very similar to those of trisomy 18, it is also referred to as pseudotrisomy 18. Despite the rarity of the condition, a distinction is still made between type I Pena-Shokeir syndrome and type II Pena-Shokeir syndrome. Type I Pena-Shokeir syndrome is also referred to as fetal akinesia/hypokinesia sequence or FADS. The other name of Pena-Shokeir syndrome type II is cerebro-oculo-facio-skeletal syndrome or COFS syndrome.
Causes
As to the cause of Pena-Shokeir syndrome, all that is known is that it is a hereditary disorder. An autosomal recessive mode of inheritance is assumed for both forms. However, since the disease is characterized only on the basis of symptoms, it is not clear whether this applies to all cases or whether spontaneous cases also occur that have an autosomal dominant mode of inheritance. The risk figures of 0.1 to 25 percent in families in which a case of the disease has already occurred show that there is by no means any certainty about the mode of inheritance. However, chromosomal aberrations can be excluded. Because of the similarities of Pena-Shokeir syndrome type I (FADS) to trisomy 18, chromosomal testing is performed, but in the case of Pena-Shokeir syndrome, it shows no abnormalities. The autosomal recessive mode of inheritance is assumed due to the fact that most cases occurred in kinship marriages and often family members suffer from it. For COFS syndrome, the second type of Pena-Shokeir syndrome, specific gene defects could be identified, but they were not uniform either. Mostly, the ERCC6/CSB gene of chromosome 10 is affected in these cases. However, defective genes on chromosome 13 or chromosome 19 were also found. In total, four genes encoding enzymes for the same DNA reaction chain may be affected here.
Symptoms, complaints, and signs
Overall, very severe health impairments occur in Pena-Shokeir syndrome that are incompatible with life. In most cases, stillbirths occur. If the child is nevertheless born alive, it survives a maximum of a few weeks in type 1 Pena-Shokeir syndrome. In type 2, death occurs within the first year of life. Pena-Shokeir syndrome type 1 (FADS) is characterized by pulmonary hypoplasia, multiple joint deformities, and facial abnormalities. The fetus exhibits severely decreased motor activity. Because the fetus cannot swallow amniotic fluid as a result, polyhydramnios occurs. Hands and feet are malformed. The patient has small ears. The distance between the eyes is enlarged. Sometimes there is also a cleft palate and a heart defect. In the vast majority of cases, the children are born too early. However, they are also too small when born on the calculated due date. Surviving children suffer from lung hypoplasia as well as short bowel syndrome, which leads to malabsorption. Only about 20 cases have been described for Pena-Shokeir syndrome type 2 or COFS syndrome. In addition to organ malformations, this disorder is characterized by severe neural and sensory dysfunction. Furthermore, photosensitivity, sensorineural hearing loss and peripheral neuropathies are common. Photosensitivity results from the defect of the DNA repair system. Death occurs within the first year of life due to respiratory infections.
Diagnosis and course of the disease
Diagnostically, Pena-Shokeir syndrome can be well differentiated from other diseases with similar symptoms. The similarities with trisomy 18 prompt chromosome testing. Chromosomal aberrations do not occur in either FADS syndrome or COFS syndrome. While in FADS syndrome the genetic cause is not known, in COFS syndrome four genes can be examined. Prenatally, the disease can already be detected by ultrasound examinations. Diagnosis is usually made by exclusion criteria.
Complications
Due to Pena-Shokeir syndrome, affected individuals usually suffer from various malformations and deformities. These may also affect the internal organs, thereby significantly reducing the quality of life and also the life expectancy of the affected person. As a rule, the Pena-Shokeir syndrome has a very negative effect on the patient’s breathing, which can lead to discomfort and complications. As a rule, the syndrome always leads to the death of the patient. For this reason, especially the relatives and parents of the child are dependent on psychological treatment to manage any severe depression and psychological discomfort that may occur. Complications usually do not occur during psychological treatment. Furthermore, the children themselves suffer from cleft palate and also heart defects. These can also cause the death of the patient. Sometimes hearing loss and severe malformations of the internal organs occur. Unfortunately, there is no treatment for Pena-Shokeir syndrome. Affected individuals usually die immediately after birth. Unfortunately, the syndrome cannot be prevented directly either. Another pregnancy is not affected by this syndrome in most cases.
When should you go to the doctor?
In the case of Pena-Shokeir syndrome, a doctor must be consulted in any case. However, usually the disease cannot be completely cured, so the born child dies a few days after birth or is born already dead. For this reason, in Pena-Shokeir syndrome, the life span can only be increased by a few days if medical treatment is given after birth. However, since the child dies, the parents and the relatives should seek psychological counseling after this incident to avoid possible psychological discomfort and complications. In this regard, contact with friends or with other sufferers of Pena-Shokeir syndrome can also be very helpful. Likewise, if pregnancy is desired again, a doctor should be consulted beforehand to clarify the risk of recurrence of Pena-Shokeir syndrome in order to avoid another stillbirth. Usually, the mother’s life span is not negatively affected by Pena-Shokeir syndrome.
Treatment and therapy
At present, treatment of Pena-Shokeir syndrome is unfortunately not possible. Surgical measures for short bowel syndrome do not lead to success, and surgical measures are usually ruled out by the severity of the symptoms alone.
Outlook and prognosis
In this rare congenital disorder, the life expectancy of infants is markedly reduced. Thus, about 30% of babies with the disease are already stillborn, while most infants born alive die as a result of their underdeveloped internal organs within a few days to months. Since this genetically inherited disease can currently neither be treated nor cured, the prospects for improvement of the symptoms are zero. Unfortunately, even complex surgical procedures usually cannot completely alleviate the symptoms and pain. Afterwards, the baby continues to require intensive care so that it can continue to develop for a few more days despite its deformities. Nevertheless, the disease offers no prospect of recovery and thus always ends fatally. Parents of affected children should consider psychotherapeutic treatments or self-help groups at an early stage in order to be able to deal with the trauma surrounding the loss of their baby. If necessary, the attending family doctor can also prescribe sedatives for the parents. If the affected family wishes to have children again after some time, counseling, prenatal screening and genetic testing would be advisable in order to be able to exclude the syndrome in subsequent children at an early stage.Since the probability of recurrence is between 0.01% and 25%, in case of genetic risk, adoption or foster care can be finally suggested to the couple.
Prevention
It is also particularly difficult to make predictions about a recurrence risk of Pena-Shokeir syndrome. The syndrome is defined based on symptoms and exclusion criteria against other conditions with similar symptoms. Although intermarriage has been frequently observed in families with cases of this disorder. In some cases, repeated cases also occur. But this is not universally true. Nevertheless, human genetic testing and counseling should be performed when the syndrome occurs. Many authors assume that autosomal recessive inheritance is involved. However, since there are no known genetic defects in FADS syndrome, a recurrence probability of 0.1 to 25 percent is given. The 0.1 percent would suggest spontaneously occurring mutations with an autosomal dominant mode of inheritance.
Follow-up
In Pena-Shokeir syndrome, the options for follow-up care are severely limited in most cases. In this case, the affected person should see a doctor at the first signs and symptoms of the syndrome in the child. However, a complete cure is usually not possible. In the case of a renewed desire to have children, a genetic examination and consultation should be carried out in the case of Pena-Shokeir syndrome, so that the syndrome does not occur again in the children. The life expectancy of the children is considerably reduced and limited by this syndrome. Most parents and relatives are dependent on intensive psychological treatment for this disease, so that it does not lead to further complications and complaints. In this context, loving and intensive conversations with one’s own family or even friends are also useful in order to prevent depression or other psychological upsets. If the child survives the birth despite the malformations, intensive surgical interventions are necessary to alleviate the symptoms. In this case, the children also depend on intensive care so that they can still develop well despite the many malformations. In general, Pena-Shokeir syndrome significantly reduces the life expectancy of the affected individual.
What you can do yourself
Pena-Shokeir syndrome is always fatal for the affected children. The most important self-help measure is for parents to seek therapeutic support early. Trauma therapy and support groups are important pillars for coping with the loss of the child. If necessary, the family doctor can prescribe sedatives or establish contact with an alternative medical practitioner who can prescribe suitable preparations for the relatives. Basically, general measures such as exercise and a balanced diet help. A full daily schedule helps to enjoy life again and overcome the trauma in the long term. If another pregnancy is planned after some time, detailed newborn screenings should be performed. This will ensure that the child is healthy. In addition, parents should seek genetic counseling and consider alternative options if there is an increased risk of recurrence of Pena-Shokeir syndrome. Adoption may be possible, or a foster child may be taken in. Before and after the birth of a sick child, the mother should maintain close contact with the gynecologist. The latter can provide information about the course of the disease and thus contribute to a speedy recovery.
