Pallister-Killian syndrome is a hereditary disease that leads to various anatomical abnormalities. In Germany and surrounding countries, only 38 cases of the syndrome are currently known. Thus, Pallister-Killian syndrome is a very rare disease.
What is Pallister-Killian syndrome?
Pallister-Killian syndrome, also called Teschler-Nicola syndrome or tetrasomy 12p mosaic, is a genetically inherited disorder. The syndrome was first diagnosed by pediatrician and geneticist Philip D. Pallister. Austrian physician Wolfgang Killian and human biologist Maria Teschler-Nicola, independently of Dr. Pallister, observed the same symptoms in four people in 1981. People with Pallister-Killian syndrome have a chromosomal change. This chromosomal change is not rare in itself. However, children affected by it usually die before birth, often even in the first trimester, so many of these pregnancies go unnoticed.
Causes
The cause of Pallister-Killian syndrome is located on the twelfth chromosome. Chromosomes are located in the nucleus of the cell. They are not actually visible there; only during cell division can their structure be clearly seen. The chromosome consists of two so-called chromatids, which are connected in the middle by the centromere, a kind of constriction. The chromosome thus looks like an X. Above the centromere, i.e. in the upper part of the X, there are two short arms. These are also called p-arms, where the p stands for petite (French for small). Below the centromere are two longer arms, the q arms. People with Pallister-Killian syndrome have the p arm in quadruplicate instead of duplicate in some of their somatic cells. The two additional p arms fuse to form a small chromosome 47, which is called isochromosome 12p. The chromosomal disorder results from defective germ cell maturation in the mother or father of the child.
Symptoms, complaints, and signs
Unlike other chromosomal disorders, such as trisomy 21, Pallister-Killian syndrome is not diagnosed before birth in most cases. Pregnancy usually proceeds without complications. Birth often occurs in a normal way and on the right date. The children have normal birth weight and size. However, the symptoms of the syndrome are varied and sometimes very severe. Due to brain dysfunction, the children have only very flaccid muscle tone. Muscle tone is the state of tension of the muscles. If it is too slack, the children can only sit up very late, for example, or have problems lifting or holding their head when breastfeeding. The unusual appearance of the children is striking. Their face is very long, the forehead is bulging. The axis of the eyelids runs obliquely upwards and outwards. The root of the nose is broad and malocclusions of the teeth cause visual conspicuities in the mouth area. Especially in the area of the temples the hair grows rather sparsely. Due to uneven pigment distribution, the skin appears blotchy, especially on the abdomen, back, arms and legs. Most children with Pallister-Killian syndrome are severely mentally retarded. They suffer from severe speech development disorders, and in some cases they remain mute. In addition to these common symptoms, the children may also have supernumerary fingers or toes. Difficult-to-set epileptic seizures, visual disturbances, heart defects and malformations of the genitals may also occur. Pallister-Killian syndrome is also typically characterized by a high susceptibility to infection.
Diagnosis and course of the disease
Diagnosis of Pallister-Killian syndrome is rather difficult. Routine chromosomal testing often erroneously reveals an unremarkable picture. For definitive detection, a skin biopsy is performed on the children. The chromosomal abnormality can then be detected in the skin cells cultured in this way. Prenatal diagnosis is also rather uncertain, because not all cells show the chromosomal defect. If by chance inconspicuous amniotic fluid cells are taken for prenatal diagnosis, the child may be born with Pallister-Killian syndrome despite this inconspicuous diagnostic finding. People with the disease are severely limited in their development and are dependent on physical assistance and intensive care for the rest of their lives. Life expectancy depends on the severity of the organ symptoms.There are people with Pallister-Killian syndrome who have lived past 40.
Complications
Due to Pallister-Killian syndrome, affected individuals suffer from various deformities and malformations. Usually, the complications and limitations for this reason also depend very much on the type and severity of these malformations. In most cases, the children suffer from muscle atrophy and a permanent state of muscle tension. Likewise, there may be discomfort in keeping the head upright. The unusual appearance of the children, especially in infancy, often leads to bullying or teasing, so that the children may also suffer from psychological complaints or depression in the process. In the oral cavity, the affected individuals have malocclusions of the teeth, which can also lead to pain. Pallister-Killian syndrome also leads to mental retardation, so that the patients are mentally very severely handicapped. For this reason, they are usually also dependent on the help of other people in their lives. Heart defects or vision problems also occur due to Pallister-Killian syndrome. A causal treatment of Pallister-Killian syndrome is not possible. With the help of various therapies, the symptoms can be partially limited. However, a completely positive course of the disease does not occur.
When should one go to the doctor?
Parents who notice muscle disorders, malformations or the typical thinning hair in their child should consult the pediatrician. Pallister-Kilian syndrome is usually detected immediately after birth or during prenatal genetic testing. If the symptoms are mild, the condition often does not become apparent until the first weeks and months of life. Treatment takes place in a special center for hereditary diseases. If this is done at an early stage, patients can lead a relatively normal life free of symptoms. Pallister-Killian syndrome is associated with various malformations and symptoms. Depending on the symptoms, it is treated by orthopedists, ophthalmologists, otologists and cardiologists, among others. Any malformations are first corrected surgically. This is followed by physiotherapeutic treatment. Since the affected children often have weak muscles, a physiotherapist must be involved. In addition, there is an increased risk of infections, which is compensated for by various vaccinations and the administration of appropriate medication. Despite all measures, patients have permanent motor limitations and need the support of a trained nurse. Therapeutic treatment supports the mental development of the sick children, who are often ostracized or bullied because of their condition. Parents should contact special schools and kindergartens at an early stage to ensure that the child receives appropriate academic support.
Treatment and therapy
Since it is a genetically inherited disorder, causal therapy of the syndrome is not possible. Therapy deals exclusively with the symptoms. Since the children are very limited in their movements and also show little initiative, individual support is very important. Different therapy approaches aim to introduce the children to the abstract world of thinking. Through different sensory impressions such as hearing, seeing and touching, the brain function should be stimulated. Through increased attention from caregivers, therapists hope to enhance the children’s social intelligence. A focus is also placed on language development. Through various linguistic activities, language comprehension is to be stimulated and expanded. Various occupational therapy and physiotherapy methods are used to treat muscular laxity. The therapy goal here is improved postural control. If the malpositioned teeth or altered nasal structure cause problems with breathing or eating, surgical intervention may be necessary. The same applies if a heart defect is present. In some cases, however, heart defects are also treated with medication. If tumors develop as a result of the disease, chemotherapeutic treatment may be necessary.
Outlook and prognosis
For conditions as rare as Pallister-Killian syndrome, the prognosis is poor if only because there has been little research and few treatment options. To date, only 70 cases have been reported worldwide.However, medical experts assume that the number of unreported cases is higher. The genetic disease is difficult to detect. The reason for the low prevalence of Pallister-Killian syndrome is a change in certain chromosomes. This usually leads to abortion of the fetus. Few children survive the pregnancy. The multitude of neurological and cognitive disorders and malformations can only be treated symptomatically, if at all. Many of those affected require lifelong assistance from caregivers. How old affected individuals live depends on the nature and severity of their disabilities. Epilepsies often develop in adolescence. Deformities or scolioses of the spine can be surgically corrected or alleviated. Musculature does not develop properly. The children are weak and often have learning disabilities. Heart defects or diaphragmatic hernias can lead to death when affected newborns undergo surgery. With good management of postnatal problems, and good care, children with Pallister-Killian syndrome can reach a median age of around forty years. The prognosis varies from individual to individual. Immune deficiencies often cause severe respiratory problems due to respiratory infections. This also causes some affected individuals to die at a young age.
Prevention
Pallister-Killian syndrome results from defective germ cell maturation in one parent. This chromosomal abnormality cannot be prevented. Thus, prevention of the disease is not possible.
Follow-up
Affected individuals with Pallister-Killian syndrome have very few, if any, special aftercare measures available to them in most cases. Therefore, affected individuals should see a physician very early in the course of this disease to prevent the occurrence of further complications and symptoms. If there is a desire to have children, genetic testing and counseling may also be useful to prevent the recurrence of Pallister-Killian syndrome. A doctor should therefore be contacted at the first signs and symptoms of the condition. Most people affected by this disease are dependent on various measures of physiotherapy or physiotherapy. Many of the exercises can be repeated at home, which speeds up the treatment. In the case of tumors, regular checks by a doctor should be carried out in order to detect other tumors at an early stage and then to treat them. Children with Pallister-Killian syndrome require intensive support and care. Especially at school, the children need special support so that they do not develop symptoms in adulthood. Whether there is a reduced life expectancy due to the disease cannot be universally predicted in this context.
What you can do yourself
Patients suffering from Pallister-Killian syndrome require ongoing home care. Children with the disease must attend a special kindergarten and later a special school for disabled children. Parents should ensure that the child is able to establish a social network at an early age in order to reduce the risk of mental health problems. In addition, the diet must be changed. Affected children should eat gentle foods to counteract the often sensitive teeth and inflammation in the oral cavity. If the child has a heart defect or suffers from tumors, constant monitoring is necessary. In the event of complications, the emergency doctor must be called immediately, as there is an acute danger to life. If the child survives the first years of life well, physiotherapy can be started, which must be created individually depending on the symptom picture. Pallister-Killian syndrome also affects posture and the ability to move individual parts of the body, which is why supportive help in the form of walking aids, wheelchairs and the like is always necessary. In most cases, structural changes have to be made at home so that the child’s special physical requirements can be met. In addition, parents must consult closely with the medical team so that the therapy can be regularly adapted to the child’s current state of health.
